ticagrelor and Hemorrhage

For acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI), the choice of the duration and kind of dual antiplatelet therapy (DAPT) offering the most accurate balance between ischemic and bleeding risk remains unknown.. A network meta-analysis was performed including all Randomized Controlled Trials (RCTs) comparing different DAPT regimens and duration in ACS patients undergoing PCI. Trial-defined MACE and major bleedings were the primary endpoints. Stroke, stent thrombosis (ST), all-cause and cardiovascular death, myocardial infarction (MI) represented secondary endpoints.. 13 RCTs encompassing 46145 patients were included. Mean age was 62 (61-64) years old, 42% being admitted with STEMI, 33% with NSTEMI and 25% with UA. The competitive arms were: clopidogrel and aspirin for 12 months (6 arms/18183 patients), clopidogrel and aspirin for 6 months (4/3329), clopidogrel and aspirin >12 months (3/2238), ticagrelor and aspirin for 12 months (6/12942) and prasugrel and aspirin for 12 months (3/9453). Trial-defined MACE and major bleedings, stroke and death were similar among the different arms. DAPT with prasugrel and aspirin for 12 months reduced MI compared to aspirin and clopidogrel for 12 months (OR 0.71, 95% CI: 0.54.0.94) and reduced the risk of ST compared to ticagrelor (OR 0.66, 95% CI: 0.49-0.90). Both prasugrel and ticagrelor reduced ST as compared to clopidogrel and aspirin for 12 months.. Different DAPT strategies yield similar risk of MACE, major bleeding, death and stroke in ACS patients. Prasugrel and aspirin for 12 months proved to be the most effective strategy regarding ST and MI.

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Hemorrhage; Humans; Middle Aged; Myocardial Infarction; Network Meta-Analysis; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Stroke; Ticagrelor

Ticagrelor may be an alternative to aspirin as it provides robust and consistent platelet inhibition. However, the effect of ticagrelor treatment in patients undergoing coronary artery bypass grafting (CABG) has not been well confirmed. We conducted a meta-analysis to appraise whether ticagrelor therapy affects outcomes in CABG patients.. We searched PubMed, Embase, EBSCO, and Cochrane databases from its inception up to 4 December 2020 for randomized controlled trials that assessed ticagrelor versus non-ticagrelor in patients undergoing CABG. The primary outcome was the incidence of saphenous vein graft (SVG) occlusion at 1 year after CABG. Secondary outcomes were SVG occlusion at 7 days, major adverse cardiovascular events (MACE), and bleeding requiring reoperation.. Seven trials including 4305 patients (2153 randomized to ticagrelor therapy and 2152 to non-ticagrelor therapy) were included. One-hundred and thirty of 1140 patients (11.4%) randomized to the ticagrelor group versus 175 of 1220 patients (14.3%) randomized to the non-ticagrelor group experienced SVG occlusion at 1 year after CABG. Compared to the control group, ticagrelor therapy yielded a significantly lower risk of SVG occlusion [RR 0.79 (0.64-0.97),. Compared with non-ticagrelor therapy, ticagrelor decreased the risk of saphenous vein graft occlusion after 1 year in patients undergoing elective CABG with saphenous vein grafting.

Topics: Aspirin; Coronary Artery Bypass; Graft Occlusion, Vascular; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Saphenous Vein; Ticagrelor; Treatment Outcome; Vascular Diseases

The aim of this study was to evaluate the efficacy and safety of antithrombotic regimens and their combinations in preventing thrombotic incidents in patients with stable atherosclerotic cardiovascular disease (S-ASCVD).. A systematic literature search was conducted in the PubMed, Embase, Cochrane Library, Scopus, and Google Scholar databases. The primary comprehensive endpoint was a major adverse cardiovascular event (MACE) composite of cardiovascular death, stroke, or myocardial infarction, while the secondary endpoints were cardiovascular death, all-cause stroke, ischemic stroke, myocardial infarction, and all-cause death. The safety endpoint was major bleeding. Bayesian network meta-regression analysis in R software was used to calculate the final effect size and to correct for the effect of follow-up time on the outcome effect size.. Twelve studies reporting 122,190 patients with eight antithrombotic regimens were included in this systematic review. For the primary composite endpoint, low-dose aspirin plus clopidogrel 75 mg (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.33-0.87) and low-dose aspirin plus rivaroxaban 2.5 mg twice daily (HR 0.53, 95% CI 0.34-0.82) showed significantly better efficacy than clopidogrel monotherapy, and the efficacy was comparable among the first two regimens. Unfortunately, none of the active regimens significantly decreased all-cause death, cardiovascular death branch, and all-cause stroke as part of the secondary endpoints. Low-dose aspirin plus ticagrelor 90 mg twice daily (HR 0.81, 95% CI 0.69-0.94) and low-dose aspirin plus ticagrelor 60 mg twice daily (HR 0.84, 95% CI 0.74-0.95) had a significant advantage in myocardial infarction compared with low-dose aspirin monotherapy, while low-dose aspirin plus 2.5 mg rivaroxaban twice daily (HR 0.62, 95% CI 0.41-0.94) was better than low-dose aspirin in the treatment of ischemic stroke. In the major bleeding branch, low-dose aspirin plus ticagrelor 90 mg twice daily (HR 2.2, 95% CI 1.70-2.90), low-dose aspirin plus ticagrelor 60 mg twice daily (HR 2.1, 95% CI 1.70-2.60), low-dose aspirin plus rivaroxaban 2.5 mg twice daily (HR 1.7, 95% CI 1.30-2.00), and rivaroxaban 5 mg twice daily (HR 1.5, 95% CI 1.20-1.90) showed higher major bleeding risk compared with low-dose aspirin.. Considering MACEs, myocardial infarction, all kinds of stroke, ischemic stroke, and major bleeding, low-dose aspirin plus rivaroxaban 2.5 mg twice daily should be considered the preferred regimen for S-ASCVD patients with low bleeding risk.

Topics: Aspirin; Atherosclerosis; Bayes Theorem; Cardiovascular Diseases; Clopidogrel; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Ischemic Stroke; Myocardial Infarction; Network Meta-Analysis; Platelet Aggregation Inhibitors; Regression Analysis; Rivaroxaban; Stroke; Ticagrelor

Currently, it is still controversial to treat stroke with ticagrelor alone. The purpose of our study was to systematically review and analyze the efficacy and safety of ticagrelor on cerebrovascular outcomes in patients with vascular risk factors.. The PubMed, Cochrane Library, and Embase databases were systematically searched using the keywords stroke, ticagrelor, clopidogrel, and aspirin to identify randomized controlled trials (RCTs). Primary outcomes included reported stroke, ischemic stroke, and complex events; the secondary outcome was hemorrhagic stroke. The safety outcomes included major bleeding events, major or minor bleeding, and intracranial bleeding. The pooled odds ratio (OR), hazard ratios (HRs), and 95% confidence interval (CI) were calculated. We used I2 statistics to assess statistical heterogeneity.. This meta-analysis included 15 RCTs involving 63,865 patients. Compared to the control group, ticagrelor reduced the risk of stroke (OR: 0.90; 95% CI: 0.81-0.99, p = 0.03; I2 = 3%), ischemic stroke (OR: 0.81; 95% CI: 0.74-0.90, p < 0.0001; I2 = 0%). Ticagrelor was not associated with an increased risk of all-cause mortality (OR: 0.94; 95% CI: 0.84-1.06, p = 0.31; I2 = 62%), major bleeding (OR: 1.06; 95% CI: 0.97-1.15, p = 0.20; I2 = 17%), hemorrhagic strokes (OR: 1.22, 95% CI: 0.76-1.96, p = 0.41; I2 = 0%), and intracranial hemorrhage (OR: 1.06; 95% CI: 0.78-1.43, p = 0.71; I2 = 12%). There was an increased risk of major or minor bleeding with ticagrelor compared to the control group (OR: 1.40; 95% CI: 1.19-1.66, p < 0.0001; I2 = 56%). Additional analyses demonstrated that ticagrelor reduced the risk of incident recurrent stroke (HR: 0.83; 95% CI: 0.75-0.93, p = 0.0009; I2 = 0%), recurrent ischemic stroke (HR: 0.79; 95% CI: 0.71-0.89, p < 0.0001; I2 = 0%) among patients with a history of acute ischemic stroke (AIS) or transient ischemic attack (TIA). There were no significant differences in safety outcomes.. Ticagrelor is slightly better than clopidogrel and aspirin in preventing stroke, especially ischemic stroke, with significant safety risks. For patients with a history of AIS/TIA, the use of ticagrelor was superior to the use of clopidogrel or aspirin in reducing the risk of subsequent stroke. We believe that ticagrelor is a potential alternative to aspirin or clopidogrel in some cases, especially for patients with CYP2C19 deficiency.

Topics: Aspirin; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

The treatment strategy for dual antiplatelet therapy (DAPT) with ticagrelor has been controversial in East Asian patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Our meta-analysis aimed to demonstrate whether intensified antithrombotic regimens with ticagrelor plus aspirin have more beneficial effects and fewer adverse events compared to those of clopidogrel plus aspirin in East Asian patients with ACS undergoing PCI.. We searched PubMed, Embase, Web of Science, ScienceDirect, Clinical Trials, Cochrane Library, and Chinese Clinical Trial Registry for randomized controlled trials (RCTs) comparing the efficacy of DAPT with ticagrelor or clopidogrel plus aspirin for secondary prevention of ACS in East Asian patients undergoing PCI. Risk ratios (RRs) and 95% confidence intervals (CIs) were used as the metrics of choice for assessing treatment effects. The primary endpoint was bleeding events, and the secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs, including cardiovascular death, nonfatal myocardial infarction [MI], and stroke), all-cause death, and definite/probable/possible stent thrombosis. The I2 index was used to assess heterogeneity.. Six RCTs involving a total of 2,725 patients met the inclusion criteria. The incidence of all bleeding events with ticagrelor was higher than that with clopidogrel (RR, 1.65; 95% CI, 1.31-2.07), but the incidence of MACCE was not significantly different between the two groups (RR, 1.08; 95% CI, 0.54-2.16). All-cause death (RR, 1.10; 95% CI, 0.67-1.79), cardiovascular death (RR, 1.42; 95% CI, 0.68-2.98), nonfatal MI (RR, 0.92; 95% CI, 0.48-1.78), stroke (RR, 1.00; 95% CI, 0.40-2.50), and stent thrombosis (RR, 0.76; 95% CI, 0.19-2.98) were not statistically different between the two groups.. Ticagrelor increased the risk of bleeding and did not increase treatment efficacy compared to that of clopidogrel in the East Asian population who have ACS treated with PCI.

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; East Asian People; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Ticagrelor; Treatment Outcome

Antiplatelet agents are among the most frequently used medications in cardiovascular medicine. Although in patients with atherosclerotic disease manifestations, in particular those treated by percutaneous coronary intervention, antiplatelet agents are beneficial for the prevention of ischemic events, they inevitably increase the risk of bleeding. Furthermore, 5-15% of patients treated by percutaneous coronary intervention may need a surgical procedure within 2 years, creating challenges to safe and effective antiplatelet drug management. Importantly, major spontaneous or procedural-related bleedings are associated with increased hospital admission, length, costs, and poor prognosis. Although the effects of other antithrombotic therapies, such as direct oral anticoagulants, can be reversed by approved specific agents, there are no approved reversal agents for any antiplatelet drugs. The fact that many antiplatelet agents, such as aspirin and thienopyridines (i.e., clopidogrel and prasugrel), bind irreversibly to their targets represents a challenge for the development of a drug-specific reversal agent. In contrast, ticagrelor is a non-thienopyridine with a plasma half-life of 7-9 h that reversely binds the P2Y

Topics: Acute Coronary Syndrome; Antibodies, Monoclonal; Clopidogrel; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor

For patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), prasugrel was recommended over ticagrelor in a recent randomized controlled trial, although more data are needed on the rationale. Here, the effects of P2Y12 inhibitors on ischemic and bleeding events in patients with NSTE-ACS were investigated.. Clinical trials that enrolled patients with NSTE-ACS were included, relevant data were extracted, and a network meta-analysis was performed.. This study included 37,268 patients with NSTE-ACS from 11 studies. There was no significant difference between prasugrel and ticagrelor for any end point, although prasugrel had a higher likelihood of event reduction than ticagrelor for all end points except cardiovascular death. Compared with clopidogrel, prasugrel was associated with decreased risks of major adverse cardiovascular events (MACE) (hazard ratio [HR], 0.84; 95% CI, 0.71-0.99) and myocardial infarction (HR, 0.82; 95% CI, 0.68-0.99) but not an increased risk of major bleeding (HR, 1.30; 95% CI, 0.97-1.74). Similarly, compared with clopidogrel, ticagrelor was associated with a reduced risk of cardiovascular death (HR, 0.79; 95% CI, 0.66-0.94) and an increased risk of major bleeding (HR, 1.33; 95% CI, 1.00-1.77; P = .049). For the primary efficacy end point (MACE), prasugrel showed the highest likelihood of event reduction (P = .97) and was superior to ticagrelor (P = .29) and clopidogrel (P = .24).. Prasugrel and ticagrelor had comparable risks for every end point, although prasugrel had the highest probability of being the best treatment for reducing the primary efficacy end point. This study highlights the need for further studies to investigate optimal P2Y12 inhibitor selection in patients with NSTE-ACS.

Topics: Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Humans; Network Meta-Analysis; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

Review the clinical outcomes of different antithrombotic strategies in patients with high bleeding risk (HBR) after percutaneous coronary intervention (PCI).. Patients with HBR after PCI include those with advanced age (e.g. >75 years of age), a prior history of major bleeding, anemia, chronic kidney disease, and those with indications for long-term anticoagulation. Strategies that successfully decrease bleeding risk in this population include shorter durations of dual antiplatelet therapy (DAPT; of 1-3 months) followed by single antiplatelet therapy with aspirin or a P2Y 12 inhibitor, or de-escalating from a more potent P2Y 12 inhibitor (prasugrel or ticagrelor) to less potent antiplatelet regimens (aspirin with clopidogrel or half-dose ticagrelor or half-dose prasugrel). Patients on DAPT, and a full dose anticoagulation for other indications, have a lower risk of major bleeding without an increase in 1-2-year adverse ischemic events, when rapidly switched from DAPT to a single antiplatelet therapy (within a week after PCI) with aspirin or clopidogrel. Longer term data on the benefits and risks of these strategies is lacking.. In patients with HBR after PCI, shorter durations of DAPT (1-3 months) decrease the risk of major bleeding without increasing the risk of adverse ischemic events.

Topics: Acute Coronary Syndrome; Anticoagulants; Aspirin; Clopidogrel; Fibrinolytic Agents; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor; Treatment Outcome

The worldwide prevalence of chronic kidney disease (CKD) has significantly increased in the past decades. Scientific reports have shown CKD to be an enhancing risk factor for the development of cardiovascular disease (CVD), which is the leading cause of premature death in patients with CKD. Clinical practice guidelines are ambiguous in view of the use of antiplatelet drugs in patients with CKD because patients with moderate-to-severe CKD were often excluded from clinical trials evaluating the efficacy and safety of anticoagulants and antiplatelet agents. In this analysis, we aimed to systematically assess the adverse cardiovascular and bleeding outcomes that were observed with ticagrelor versus clopidogrel use in patients with CKD and cardiovascular disease.. Electronic databases including Web of Science, Google Scholar, http://www.. gov , Cochrane database, EMBASE, and MEDLINE were carefully searched for English-based articles comparing ticagrelor with clopidogrel in patients with CKD. Adverse cardiovascular outcomes and bleeding events were the endpoints in this study. The latest version of the RevMan software (version 5.4) was used to analyze the data. Risk ratios (RR) with 95% confidence intervals (CI) were used to represent the data post analysis.. A total of 15,664 participants were included in this analysis, whereby 2456 CKD participants were assigned to ticagrelor and 13,208 CKD participants were assigned to clopidogrel. Our current analysis showed that major adverse cardiac events (MACEs) (RR: 0.85, 95% CI: 0.71-1.03; P = 0.09), all-cause mortality (RR: 0.82, 95% CI: 0.57- 1.18; P = 0.29), cardiovascular death (RR: 0.83, 95% CI: 0.56-1.23; P = 0.35), myocardial infarction (RR: 0.87, 95% CI: 0.70-1.07; P = 0.19), ischemic stroke (RR: 0.80, 95% CI: 0.58-1.11; P = 0.18), and hemorrhagic stroke (RR: 1.06, 95% CI: 0.38-2.99; P = 0.91) were not significantly different in CKD patients who were treated with ticagrelor versus clopidogrel. Thrombolysis in myocardial infarction (TIMI)-defined minor (RR: 0.89, 95% CI: 0.52-1.53; P = 0.68) and TIMI major bleeding (RR: 1.10, 95% CI: 0.69-1.76; P = 0.67) were also not significantly different. However, bleeding defined according to the academic research consortium (BARC) bleeding type 1 or 2 (RR: 1.95, 95% CI: 1.13-3.37; P = 0.02) and BARC bleeding type 3 or 5 (RR: 1.70, 95% CI: 1.17-2.48; P = 0.006) were significantly higher with ticagrelor.. When compared with clopidogrel, even though ticagrelor was not associated with higher risk of adverse cardiovascular outcomes in these patients with CKD, it was associated with significantly higher BARC bleeding. Therefore, the safety outcomes of ticagrelor still require further evaluation in patients with CKD. Nevertheless, this hypothesis should only be confirmed with more powerful results that could usually only be achieved using large-scale randomized trials.

Topics: Acute Coronary Syndrome; Cardiovascular Diseases; Clopidogrel; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Renal Insufficiency, Chronic; Ticagrelor; Treatment Outcome

Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel was recommended as the secondary prevention of minor ischemic stroke or transient ischaemic attack (TIA). However, genetic polymorphisms of CYP2C19 had been identified as the major cause of poor responsiveness to clopidogrel. Ticagrelor, unlike clopidogrel, did not depend on metabolic activation, but it remained unclear whether ticagrelor was superior to clopidogrel in ischemic stroke. We performed a network meta-analysis to compare the efficacy and safety of ticagrelor, clopidogrel, and aspirin in the minor ischemic stroke and TIA populations.. Databases of Cochrane Library, ClinicalTrials.gov, and PubMed were searched up to June 19, 2023. Randomized controlled trials (RCTs) assessing antiplatelet drugs for minor stroke or TIA were included. Statistical processing was conducted by using multivariate meta-analysis routines of STATA.. Seven RCTs were included involving 41,745 participants. There was no significant difference between the two DAPTs in preventing stroke recurrence (OR, 1.16; 95% CI, 0.93-1.44), ischemic stroke recurrence (OR, 1.16; 95% CI, 0.93-1.45), and major hemorrhage (OR, 1.22; 95% CI, 0.62,2.39). Compared with aspirin alone, the two DAPT regimen reduced the risk of stroke recurrence (clopidogrel: OR, 0.69; 95% CI, 0.60-0.80, ticagrelor: OR, 0.66; 95% CI, 0.49-0.87) and ischemic stroke recurrence, but increased the incidence of major hemorrhage (clopidogrel: OR, 2.05; 95% CI, 1.22- 3.77; ticagrelor: OR, 2.55; 95% CI, 1.25-4.99). Despite being associated with a higher risk of any bleeding, ticagrelor did not impact the composite of vascular events or mortality. While ticagrelor and aspirin reduced the risk of ischemic stroke recurrence (OR, 0.77; 95% CI, 0.63- 0.92) without increasing the risk of major bleeding (OR 0.94; 95% CI 0.45-1.95) in the Asian population mainly Chinese.. DAPT was superior to aspirin in stroke prevention, but little difference existed between the two DAPT regimens. Asian population mainly Chinese may benefit from DAPT with aspirin and ticagrelor. But further head-to-head RCTs are needed to validate the study results.

Topics: Aspirin; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Network Meta-Analysis; Platelet Aggregation Inhibitors; Stroke; Ticagrelor

Limited data comparing prasugrel and ticagrelor in acute coronary syndrome are available. Online databases, including MEDLINE and Cochrane Central, were queried to compare these drugs. The primary outcomes of this meta-analysis are myocardial infarction (MI), all-cause mortality, cardiovascular mortality, noncardiovascular mortality, stent thrombosis, and stroke. The secondary outcome is major bleeding. A total of 9 studies, including 94,590 patients (prasugrel group = 32,759; ticagrelor group = 61,831), were included in this meta-analysis. The overall mean age was 62.73 years, whereas the mean age for the ticagrelor and prasugrel groups was 63.80 and 61.65 years, respectively. Prasugrel is equally effective as compared with ticagrelor in preventing MI. There was no difference between the 2 groups regarding all-cause mortality, stent thrombosis, stroke, or major bleeding. In patients with acute coronary syndrome, prasugrel is equally effective when compared with ticagrelor in preventing MI.

Topics: Acute Coronary Syndrome; Hemorrhage; Humans; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Stroke; Thrombosis; Ticagrelor; Treatment Outcome

A systematic review and network meta-analysis (NMA) were conducted to explore the efficacy and safety of different antiplatelet or anticoagulation drugs in chronic coronary syndromes patients.. Electronic databases (Pubmed, Embase and Cochrane databases) were systematically searched to identify randomized controlled trials evaluating different antiplatelet or anticoagulation drugs (aspirin, aspirin + clopidogrel, aspirin + clopidogrel + cilostazol, clopidogrel/prasugrel + aspirin, aspirin + rivaoxaban 2.5 mg, aspirin + ticagrelor 60 mg, aspirin + ticagrelor 90 mg, clopidogrel or rivroxaban 5 mg) versus placebo for treatment chronic coronary syndromes patients. Outcomes included major adverse cardiovascular events, all cause death, major bleeding and myocardial infarction. A random-effect Bayesian NMA was conducted for outcomes of interest, and results were presented as odds ratios (ORs) and 95% credible intervals. The NMA was performed using R Software with a GeMTC package. A Bayesian NMA was performed and relative ranking of agents was assessed using surface under the cumulative ranking probabilities.. Ten randomized controlled trials met criteria for inclusion and finally included in this NMA. In head-to-head comparison, no significant difference was observed between all antithrombotic treatment strategies with respect to primary endpoint of major adverse cardiovascular events. In head-to-head comparison, no significant difference was observed between all antithrombotic treatment strategies with respect to all cause death. Clopidogrel/prasugrel + aspirin (OR = 3.8, 95% credible intervals [CrI]: 1.3-12.0, P < .05) and aspirin + rivaroxaban 2.5 mg (OR = 3.1, 95%CrI: 1.1-9.5, P < .05) was associated with an increase of the major bleeding. Compared with aspirin alone, aspirin + clopidogrel (OR = 0.42, 95%CrI: 0.22-0.76, P < .05) and aspirin + ticagrelor 90 mg (OR = 0.42, 95%CrI: 0.17-0.95, P < .05) was associated with a decrease of the myocardial infarction.. Myocardial infarction was significantly lower when adding clopidogrel or ticagrelor 90 mg to aspirin than those in the aspirin alone group. However, clopidogrel/prasugrel and rivaroxaban 2.5 mg was associated with an increase of the major bleeding than aspirin alone.

Topics: Acute Coronary Syndrome; Anticoagulants; Aspirin; Bayes Theorem; Clopidogrel; Fibrinolytic Agents; Hemorrhage; Humans; Myocardial Infarction; Network Meta-Analysis; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Rivaroxaban; Ticagrelor; Treatment Outcome

We aimed to evaluate the clinical benefits of a de-escalation strategy from prasugrel or ticagrelor to clopidogrel versus continuation of prasugrel or ticagrelor along with aspirin in both strategies for patients presenting with acute coronary syndrome (ACS) and treated with percutaneous coronary intervention (PCI), and to analyze the effect of the recently published randomized clinical trial (RCT) by Park et al., which included the largest sample size ever and the largest switched number of patients, on current guidelines and practices.. The PubMed, EMBASE, Scopus, Web of Science, Cochrane Central, and Google Scholar databases were searched systematically from inception to May 2021 by using the search terms ('de-escalation' OR 'switching') AND ('antiplatelet' OR 'clopidogrel' OR 'ticagrelor' OR 'prasugrel') AND ('percutaneous coronary intervention' OR 'PCI'' OR 'Acute coronary syndrome' OR 'ACS').. We included RCTs that reported the primary outcomes, i.e. net clinical benefits and Bleeding Academic Research Consortium (BARC) type 2 or higher bleeding. A combination of both ischemic and bleeding events was defined as a net clinical benefit.. A total of four RCTs were included, with 5952 patients. A random-effects meta-analysis revealed that a de-escalation strategy was associated with lower ischemic and bleeding events (net clinical benefits; risk ratio [RR] 0.63, 95% confidence interval [CI] 0.47-0.85; p = 0.003), and lower BARC type 2 or higher bleeding (RR 0.51, 95% CI 0.29-0.91; p = 0.02) when compared with a continuation strategy.. The current guidelines recommend potent P2Y12 prasugrel or ticagrelor for 12 months despite their association with a high risk of bleeding. Our meta-analysis updates cardiologists, providing them with the best available evidence in managing patients with ACS who underwent PCI.. Among patients with ACS treated with PCI, a de-escalation strategy (prasugrel or ticagrelor to clopidogrel) is associated with lower ischemic and bleeding events (net clinical benefits) and lower BARC type 2 or higher bleeding; however, due to the limited number of included studies, further high-quality studies are needed to establish the clinical efficacy of the de-escalation strategy.

Topics: Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Ticagrelor; Treatment Outcome

The combination of oral anticoagulants with platelet inhibitors has been widely investigated in patients with coronary stenting and concomitant atrial fibrillation. In these patients, default therapy after percutaneous coronary intervention in acute coronary syndrome is clopidogrel plus non-vitamin K antagonist oral anticoagulant, omitting aspirin. However, in view of the high thromboembolic risk associated with acute coronary syndrome and the number of poor metabolizers for clopidogrel, investigation of alternative P2Y12-inhibitors is mandatory. This prospective, multicenter, open-label, registry-based, randomized, controlled trial aims to show the non-inferiority of dabigatran plus ticagrelor versus dabigatran plus clopidogrel in patients on chronic anticoagulants who undergo percutaneous coronary intervention in acute coronary syndrome. The primary end point is major bleeding as defined by the Bleeding Academic Research Consortium bleeding definition.

Topics: Acute Coronary Syndrome; Anticoagulants; Clopidogrel; Dabigatran; Drug Therapy, Combination; Hemorrhage; Humans; Multicenter Studies as Topic; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Randomized Controlled Trials as Topic; Ticagrelor; Warfarin

Antiplatelet medications remain a cornerstone of therapy for atherosclerotic cardiovascular and cerebrovascular diseases. In primary prevention (patients with cardiovascular risk factors but no documented events, symptoms or angiographic disease), there is little evidence of benefit of any antiplatelet therapy, and such therapy carries the risk of excess bleeding. Where there is documented disease (secondary prevention), stable patients benefit from long-term antiplatelet monotherapy, aspirin being first choice in those with coronary heart disease and clopidogrel in those with cerebrovascular disease; moreover, recent evidence shows that low-dose rivaroxaban in combination with aspirin confers added benefit, in patients with stable cardiovascular and peripheral arterial disease. In patients with acute cerebrovascular disease, aspirin combined with clopidogrel reduces subsequent risk, while in acute coronary syndrome, dual antiplatelet therapy comprising aspirin and a P2Y

Topics: Acute Coronary Syndrome; Aspirin; Cardiovascular Diseases; Clopidogrel; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor

The risk of bleeding is high in East Asians, whether East Asian patients with acute coronary syndrome choose ticagrelor or clopidogrel is still controversial. In this study, PubMed, EMBASE, Cochrane Library database, and other sources were systematically searched. The primary efficacy outcome was all-cause death, the primary safety outcomes were any bleeding, PLATO major bleeding, and fatal bleeding. The secondary outcomes included vascular-cause death, myocardial infarction, stent thrombosis, stroke, and dyspnea. A total of 8 randomized controlled trials with 3597 patients met inclusion criteria. Compared with clopidogrel, ticagrelor had significantly higher incidence of any bleeding [risk ratio (RR), 1.63; 1.33-1.99; P < 0.00001], PLATO major bleeding (RR 1.56; 1.15-2.12; P = 0.004), and dyspnea (RR 2.60; 1.68-4.00; P < 0.00001). However, ticagrelor was associated with a significantly reduced risk of stent thrombosis (RR 0.42; 0.19-0.92; P = 0.03). There was no significant difference in the risk of all-cause death (RR 0.87; 0.64-1.24; P = 0.44), fatal bleeding (RR 2.49; 0.79-7.86; P = 0.12), vascular-cause death (RR 0.88; 1.60-0.30; P = 0.52), myocardial infarction (RR 0.89; 0.65-1.23; P = 0.49), and stroke (RR 0.84; 0.47-1.50; P = 0.56) between the 2 groups. The present findings demonstrated that ticagrelor was associated with a higher risk of any bleeding, PLATO major bleeding, and dyspnea compared with clopidogrel in East Asian patients with acute coronary syndrome. However, it significantly reduced the risk of stent thrombosis. (Registered by PROSPERO, CRD42021255215).

Topics: Acute Coronary Syndrome; Asian People; Clopidogrel; Dyspnea; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Thrombosis; Ticagrelor; Treatment Outcome

Topics: Acute Coronary Syndrome; Aspirin; Canada; Drug Therapy, Combination; Europe; Female; Hemorrhage; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Risk Factors; Ticagrelor

The efficacy and safety of clopidogrel compared with ticagrelor as part of dual antiplatelet therapy in patients, and in older patients, with acute coronary syndrome is reviewed. PubMed, Embase, the Cochrane Library, MEDLINE, and HTA databases were searched (September 2, 2020) for randomized controlled trials (RCTs). Pooled risk differences (clopidogrel minus ticagrelor) were estimated using random-effects meta-analyses, and certainty of evidence was assessed according to Grading of Recommendations Assessment, Development, and Evaluation. In all, 29 RCTs were identified. The risk difference for all-cause mortality was 0.6% (-0.03% to 1.3%), cardiovascular (CV) mortality: 0.6% (95% confidence interval: 0.01% to 1.1%), myocardial infarction (MI): 0.9% (0.4% to 1.3%), stent thrombosis: 0.7% (0.4 to 1.1%), clinically significant bleeding: -1.9% (-3.7% to -0.2%), major bleeding: -0.9% (-1.6% to -0.1%), and dyspnea: -5.8% (-7.7% to -3.8%). In older patients, there were no differences between the comparison groups regarding all-cause mortality, CV mortality, and MI, whereas the risk of clinically significant bleeding and major bleeding was lower in the clopidogrel group, -5.9% (-11 to -0.9%, 1 RCT) and -2.4% (-4.4% to -0.3%), respectively. Compared with ticagrelor, clopidogrel may result in little or no difference regarding all-cause mortality. Although not evident in older patients, it cannot be excluded that clopidogrel may be slightly less efficient in reducing the risk of CV mortality and MI, whereas ticagrelor is probably more efficacious in reducing the risk of stent thrombosis. Clopidogrel results in a reduced risk of dyspnea and clinically significant bleeding and in older people probably in a reduced risk of major bleeding.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Dyspnea; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Thrombosis; Ticagrelor; Treatment Outcome

Topics: Hemorrhage; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Stroke; Ticagrelor

Studies show inconsistent results regarding the impact of CYP2C19 genotype on the pharmacodynamics (PD) and clinical outcomes of ticagrelor. With the implementation of genotype-guided individualized antiplatelet therapy, the association between CYP2C19 polymorphism and the efficacy and safety of ticagrelor for patients is still worthy of exploring and studying.. This systematic review protocol has been registered in the PROSPERO network (No. CRD 42020158920). Electronic databases of PubMed, EmBase, and the Cochrane Library were systematically searched from inception to January 6th, 2022 to select studies investigating the impact of CYP2C19 genotype on PD and clinical outcomes of ticagrelor. The results were presented as odds ratio (OR) or weight mean difference with its 95% confidence interval (CI) by using the random-effects model. Trial sequential analysis (TSA) was used to control risk of random errors and detect the robustness of outcomes.. Eight studies recruited a total of 6405 patients treated with ticagrelor. Mostly trials reported no significant effect of any or no CYP2C19 loss-of-function (LOF) allele (*2 or *3) on all the endpoints. Compared with no LOF allele carriers, subgroup analysis suggested any LOF allele in Asian patients was associated with a significant decreased risk of bleeding events (OR: 0.41; 95% CI: 0.22-0.75; P = 0.004). Furthermore, any LOF allele carriers didn't yield any impact on the risk of MACEs (OR: 1.11; 95% CI: 0.76-1.64; P = 0.586), stroke (OR: 1.71; 95% CI: 0.99-2.96; P = 0.054), definite stent thrombosis (OR: 0.88; 95% CI: 0.17-4.60; P = 0.882), bleeding (OR: 0.63; 95% CI: 0.27-1.46; P = 0.281), myocardial infarction (OR: 0.81; 95% CI: 0.30-2.20; P = 0.682), and revascularization (OR: 0.81; 95% CI: 0.33-2.00; P = 0.649) in all patients. The results of TSA were indicated that more further trials would be required.. This qualitative and quantitative study suggested Asian patients carrying any CYP2C19 LOF allele might have a lower risk of bleeding events comparing with no LOF allele carriers when treated with ticagrelor. However, we did not prove an important role of CYP2C19 genotype on the risk of PD and clinical endpoints in the whole cohort. In future, more large-scale prospective studies and more different ethnic populations should be included.

Topics: Clopidogrel; Cytochrome P-450 CYP2C19; Genotype; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Prospective Studies; Ticagrelor; Treatment Outcome

The relative safety and efficacy of de-escalation, extended duration (ED) (>12-months), and standard dual antiplatelet therapy for 12-months (DAPT-12) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains controversial.. Online databases were queried to identify relevant randomized control trials (RCTs). ED-DAPT, high-potency (HP) DAPT, shorter duration (SD) DAPT, and low-dose (LD) DAPT were compared with DAPT-12. A trial sequential, bivariate, influential, and frequentist network meta-analysis (NMA) was performed to determine the pooled estimates. A total of 30 RCTs comprising 81 208 (40 839 experimental, 40 369 control arm) patients with CAD were included in the quantitative analysis. On NMA, compared with DAPT-12, all types of de-escalation, HP-DAPT-12, and ED-DAPT strategies had a statistically non-significant difference in the incidence of MACE at a median follow-up of 1-year. Similarly, there was no significant difference in the incidence of stroke, stent thrombosis, target lesion revascularization (TLR), target vessel revascularization (TVR), and all-cause mortality between DAPT-12 and all other strategies. The network estimates showed a significantly lower incidence of major bleeding with DAPT for 3-months followed by P2Y12-inhibitor monotherapy (RR 0.62, 95% CI 0.45-0.84), while a higher risk of bleeding with HP-DAPT for 12 months (RR 1.55, 95% CI 1.16-2.06). The net clinical benefit and rankograms also favoured DAPT-3 (P2Y12) and discouraged the use of HP-DAPT-12 and ED-DAPT. A subgroup analysis of 19 RCTs restricted to patients who presented with acute coronary syndrome (ACS) mirrored the findings of pooled analysis. A sensitivity analysis revealed no influence of any individual study or individual strategy on net ischemic estimates. The trial sequential analysis (TSA) illustrated a consistently non-significant difference at the interim analysis of trials, reaching the futility area for MACE, while the cumulative Z-values line surpassed the monitoring boundary as well as the required information size for major bleeding favouring de-escalation strategy.. DAPT for three months followed by ticagrelor-only and use of aspirin + clopidogrel after a short period of high potency DAPT appears to be a safe strategy for treating post-PCI patients. However, given the methodological limitations and inclusion of a small number of trials in novel de-escalation strategies, these findings need validation by future large scale RCTs.

Topics: Aspirin; Clopidogrel; Coronary Artery Disease; Hemorrhage; Humans; Network Meta-Analysis; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor

For patients after percutaneous coronary interventions (PCI), clopidogrel combined with aspirin is a conventional dual antiplatelet therapy (DAPT) method. Because the genetic polymorphism of CYP2C19 gene leads to clopidogrel resistance, guidelines for antiplatelet recommendations in CYP2C19 of ultrarapid metabolizers (UM), extended metabolizers (EM) and poor metabolizers (PM) are clear. However, there is no clear recommendation as to whether ticagrelor or double dose clopidogrel is the best antiplatelet regimen for CYP2C19 of intermediate metabolizers (IM). To evaluate the efficacy and safety of ticagrelor (combined with aspirin) and high-dose clopidogrel (combined with aspirin) in patients after PCI with CYP2C19 loss-of-function (LOF) alleles.. We searched the following databases to select RCTs of comparing ticagrelor with high-dose clopidogrel in patients after PCI with CYP2C19 LOF alleles: CNKI, Wanfang Data, PubMed, Clinical trials, Cochrane, Web of Science and Embase. Major adverse cardiovascular events (MACEs), platelet function and TIMI bleeding event were defined as the outcomes. revman 5.3 software was used to perform meta-analysis.. A total of 14 RCTs with 2351 patients were enrolled. Meta-analysis showed that compared with high-dose clopidogrel, ticagrelor had reduced incidence of MACEs (OR = 0.32, 95% Cl: 0.23-0.44, p < 0.00001), stent thrombosis (OR: 0.24, 95%CI: 0.13-0.44, p < 0.00001), myocardial infarction OR: 0.42, 95%CI: 0.22-0.80, p = 0.008), revascularization (OR: 0.29, 95%CI: 0.10-0.82, p = 0.02) and unstable angina (OR: 0.47, 95%CI: 0.29-0.77, p = 0.003) in patients after PCI with CYP2C19 LOF alleles. A subgroup analysis showed that ticagrelor reduced the risk of MACEs compared with high-dose clopidogrel regardless of the type of metabolizer. Compared with high-dose clopidogrel, ticagrelor significantly reduced the risk of MACE with longer follow-up period (more than 3 months) without increasing the risk of bleeding (OR: 0.89, 95%CI: 0.53-1.49, p = 0.30), while elevated dyspnoea (OR: 5.62, 95%CI: 3.07-10.28, p < 0.00001).. For patients carrying CYP2C19 LOF alleles after PCI, ticagrelor may be better than high-dose clopidogrel in reducing the risk of MACEs, while dyspnoea incidents should be alerted.

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Cytochrome P-450 CYP2C19; Dyspnea; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Ticagrelor; Treatment Outcome

Currently, potent P2Y. To compare oral P2Y. We systematically searched PubMed, Cochrane Central Register of Controlled Trials and Web of Science to identify studies that compared different oral P2Y. Nine studies (n=35 441 patients) were included in the systematic review. There was no difference between prasugrel and ticagrelor in the composite cardiovascular end point (prasugrel vs ticagrelor HR=0.80, 95% CI=0.61 to 1.06) in all patients with NSTE-ACS. In patients intended to receive invasive management, prasugrel resulted in a reduction of the composite cardiovascular end point both versus clopidogrel (HR=0.76, 95% CI=0.61 to 0.95) and ticagrelor (HR=0.74, 95% CI=0.56 to 0.98). Inconsistency was moderate and non-significant (I. In patients with NSTE-ACS intended to receive invasive management, an antiplatelet strategy based on prasugrel is more efficient than a similar strategy based on ticagrelor on a moderate level of evidence. This analysis supports the current recommendations by the ESC guidelines.

Topics: Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Humans; Network Meta-Analysis; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor

 To investigate outcomes with selective, clopidogrel-based therapies versus conventional treatment in patients undergoing percutaneous coronary intervention (PCI), especially for acute coronary syndrome..  Safety and efficacy of alternative, selective, clopidogrel-based therapies after PCI are not robustly established..  We performed a study-level meta-analysis on six randomized trials investigating selective clopidogrel-based therapies (three on unguided de-escalation,.  The incidence of major bleeding and MACE was similar in the selective, clopidogrel-based therapy versus the conventional treatment arm (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.51-1.01,.  As compared with prasugrel/ticagrelor treatment, alternative, selective, clopidogrel-based approaches provide a similar protection from cardiovascular events, reduce the risk of any bleeding, and are associated with a greater net benefit. These beneficial effects were prevalent with unguided de-escalation to clopidogrel.

Topics: Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor; Treatment Outcome

The effectiveness and safety of administration of ticagrelor simultaneously with fibrinolytic agents in STEMI patients remain unclear.. This study aimed to investigate the effectiveness and safety of tenecteplase against alteplase in patients with STEMI receiving a loading dose of ticagrelor.. We conducted a cross-sectional study in patients with STEMI who were reperfused with fibrinolytic. The study included 150 patients (ages 18 to 75 years) administered tenecteplase or alteplase and concomitantly given ticagrelor [180 mg loading dose, 90 mg bid (bis in die)]. Patients who had active major bleeding, died, and who were decided to have a CABG surgery as a result of coronary angiography were excluded. Patients who underwent facilitated-PCI with fibrinolysis continued to receive ticagrelor without switching to clopidogrel. The MACE (in-hospital death, TIMI flow grade, major bleeding) rates of the two groups were compared.. The study consisted of 150 patients, comprising 99 (66%) men and 51 women (34%) with a mean age of 60,33 ± 13,83 years. Patients were divided into two groups according to the thrombolytic therapy: alteplase (n = 60) and tenecteplase (n = 90). The major adverse cardiac events (MACE) (45% vs 22.2%), bleeding (11.7% vs 2.2%), hypertension (51.7% vs 30%), atrial fibrillation (26.7% vs 12.2%), left ventricular hypertrophy (26.7% vs 10%), CRP (p < 0.001) were significantly higher and the recanalization (66.7% vs 85.4%), hematocrit (p = 0.03) were significantly lower in the alteplase group compared to the tenecteplase group. No significant differences were found between the two groups about in-hospital mortality (p = 0.151). Kaplan Meier analysis was performed in terms of MACE (TIMI flow grade 1, major bleeding, in-hospital mortality) rates during the follow-up period (Log-rank test, p = 0.032). Patients who received tenecteplase treatment had a lower MACE, according to a Kaplan-Meier analysis.. The administration of tenecteplase in STEMI patients who received a loading dose with ticagrelor resulted in a significant reduction in MACE compared to alteplase. Larger multi-center studies are warranted to investigate the effect of tenecteplase treatment on clinical results.

Topics: Adolescent; Adult; Aged; Cross-Sectional Studies; Female; Fibrinolytic Agents; Hemorrhage; Hospital Mortality; Humans; Infant, Newborn; Male; Middle Aged; Percutaneous Coronary Intervention; ST Elevation Myocardial Infarction; Tenecteplase; Ticagrelor; Tissue Plasminogen Activator; Treatment Outcome; Young Adult

Although current guidelines recommend ticagrelor to clopidogrel for patients with acute coronary syndrome, its benefit and risk are unclear for East Asians. This meta-analysis was performed to assess the efficacy and safety of ticagrelor in East Asian patients with acute coronary syndrome.. Medline, EMBASE, and Cochrane Databases were searched from inception to July, 2021, for randomized controlled trials comparing ticagrelor with clopidogrel in East Asian patients with acute coronary syndrome. Major adverse cardiovascular events and bleeding events were assessed by using Mantel-Haenszel-pooled risk ratio and 95% con- fidence interval.. Five randomized controlled trials identified 2752 patients with acute coronary syndrome. Compared with clopidogrel, ticagrelor had no statistical difference of major adverse cardiovascular events (RR 0.87; 95% CI 0.52-1.45; P = .58), all cause death (RR 0.90, 95% CI 0.62-1.32; P = .60), cardiovascular death (RR 0.90, 95% CI 0.47-1.72; P = .74), myo- cardial infarction (RR 0.91, 95% CI 0.52-1.58; P = .73), and stroke (RR 0.87, 95% CI 0.48-1.57; P = .64). Despite ticagrelor did not increase the incidence of fatal bleeding (RR 2.49, 95% CI 0.79-7.87; P = 0.12), the risks of all bleeding (RR 1.71, 95% CI 1.36-2.16; P < .00001), major bleeding (RR 1.51, 95% CI 1.12-2.04; P = .007), non-coronary artery bypass grafting major bleeding (RR 1.83, 95% CI 1.23-2.71; P = .003), and minor bleeding (RR 1.92, 95% CI 1.40-2.64; P < .0001) were significantly higher.. Although there was no significant difference in the incidence of fatal bleed- ing, ticagrelor displayed similar efficacy and dramatically increased the risk of otherbleeding events.

Topics: Acute Coronary Syndrome; Asian People; Clopidogrel; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Ticagrelor; Treatment Outcome

The 2020 European Society of Cardiology guidelines do not recommend pretreatment for nonST-segment elevation myocardial infarction (NSTEMI) patients with unclear coronary anatomy, which is inconsistent with our routine preoperative approach to loading P2Y12 receptor inhibitors (e.g., preoperative loading of 300 mg of clopidogrel).. The purpose of our study was to compare the safety and effectiveness of P2Y12 inhibitors administered before coronary angiography or at least before percutaneous coronary intervention (PCI) with during or after PCI.. Cochrane, PubMed, and Embase databases were searched. The primary effect endpoint and safety endpoint were any-cause death and major bleeding, respectively. Major adverse cardiovascular events, myocardial infarction and revascularization were also analyzed.. Our search identified 9 trials. P2Y12 inhibitor pretreatment was associated with lower death from any cause (OR 0.62, 95% CI 0.53-0.72, P < 0.00001) without increasing the risk of bleeding (OR 1.02, 95% CI 0.80-1.30, P = 0.89). However, prasugrel or ticagrelor pretreatment was not associated with a lower risk of mortality (OR 0.70, 95% CI 0.31-1.59, P = 0.40) and increased the risk of bleeding (OR 1.67, 95% CI 1.10-2.54, P = 0.02).. In summary, clopidogrel pretreatment was associated with significantly lower mortality, major adverse cardiovascular events, myocardial infarction and revascularization with no increase in major bleeding. However, these advantages were not observed with prasugrel or ticagrelor pretreatment.

Topics: Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

The role of ticagrelor with or without aspirin after coronary artery bypass graft surgery remains unclear.. To compare the risks of vein graft failure and bleeding associated with ticagrelor dual antiplatelet therapy (DAPT) or ticagrelor monotherapy vs aspirin among patients undergoing coronary artery bypass graft surgery.. MEDLINE, Embase, and Cochrane Library databases from inception to June 1, 2022, without language restriction.. Randomized clinical trials (RCTs) comparing the effects of ticagrelor DAPT or ticagrelor monotherapy vs aspirin on saphenous vein graft failure.. Individual patient data provided by each trial were synthesized into a combined data set for independent analysis. Multilevel logistic regression models were used.. The primary analysis assessed the incidence of saphenous vein graft failure per graft (primary outcome) in RCTs comparing ticagrelor DAPT with aspirin. Secondary outcomes were saphenous vein graft failure per patient and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events. A supplementary analysis included RCTs comparing ticagrelor monotherapy with aspirin.. A total of 4 RCTs were included in the meta-analysis, involving 1316 patients and 1668 saphenous vein grafts. Of the 871 patients in the primary analysis, 435 received ticagrelor DAPT (median age, 67 years [IQR, 60-72 years]; 65 women [14.9%]; 370 men [85.1%]) and 436 received aspirin (median age, 66 years [IQR, 61-73 years]; 63 women [14.5%]; 373 men [85.5%]). Ticagrelor DAPT was associated with a significantly lower incidence of saphenous vein graft failure (11.2%) per graft than was aspirin (20%; difference, -8.7% [95% CI, -13.5% to -3.9%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001) and was associated with a significantly lower incidence of saphenous vein graft failure per patient (13.2% vs 23.0%, difference, -9.7% [95% CI, -14.9% to -4.4%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001). Ticagrelor DAPT (22.1%) was associated with a significantly higher incidence of BARC type 2, 3, or 5 bleeding events than was aspirin (8.7%; difference, 13.3% [95% CI, 8.6% to 18.0%]; OR, 2.98 [95% CI, 1.99 to 4.47]; P < .001), but not BARC type 3 or 5 bleeding events (1.8% vs 1.8%, difference, 0% [95% CI, -1.8% to 1.8%]; OR, 1.00 [95% CI, 0.37 to 2.69]; P = .99). Compared with aspirin, ticagrelor monotherapy was not significantly associated with saphenous vein graft failure (19.3% vs 21.7%, difference, -2.6% [95% CI, -9.1% to 3.9%]; OR, 0.86 [95% CI, 0.58 to 1.27]; P = .44) or BARC type 2, 3, or 5 bleeding events (8.9% vs 7.3%, difference, 1.7% [95% CI, -2.8% to 6.1%]; OR, 1.25 [95% CI, 0.69 to 2.29]; P = .46).. Among patients undergoing coronary artery bypass graft surgery, adding ticagrelor to aspirin was associated with a significantly decreased risk of vein graft failure. However, this was accompanied by a significantly increased risk of clinically important bleeding.

Topics: Aged; Aspirin; Coronary Artery Bypass; Female; Graft Occlusion, Vascular; Hemorrhage; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Saphenous Vein; Ticagrelor; Treatment Outcome

High-quality evidence from trials directly comparing single antiplatelet therapies in symptomatic peripheral arterial disease (PAD) to dual antiplatelet therapies or acetylsalicylic acid (ASA) plus low-dose rivaroxaban is lacking. Therefore, we conducted a network meta-analysis on the effectiveness of all antithrombotic regimens studied in PAD.. A systematic search was conducted to identify randomized controlled trials. The primary endpoints were major adverse cardiovascular events (MACE) and major bleedings. Secondary endpoints were major adverse limb events (MALE) and acute limb ischaemia (ALI). For each outcome, a frequentist network meta-analysis was used to compare relative risks (RRs) between medication and ASA. ASA was the universal comparator since a majority of studies used ASA as in the reference group.. Twenty-four randomized controlled trials were identified including 48,759 patients. With regard to reducing MACE, clopidogrel [RR 0.78, 95% confidence interval (CI) 0.66-0.93], ticagrelor (RR 0.79, 95% CI 0.65-0.97), ASA plus ticagrelor (RR 0.79, 95% CI 0.64-0.97), and ASA plus low-dose rivaroxaban (RR 0.84, 95% CI 0.76-0.93) were more effective than ASA, and equally effective to one another. As compared to ASA, major bleedings occurred more frequently with vitamin K antagonists, rivaroxaban, ASA plus vitamin K antagonists, and ASA plus low-dose rivaroxaban. All regimens were similar to ASA concerning MALE, while ASA plus low-dose rivaroxaban was more effective in preventing ALI (RR 0.67, 95% CI 0.55-0.80). Subgroup analysis in patients undergoing peripheral revascularization revealed that ≥ 3 months after intervention, evidence of benefit regarding clopidogrel, ticagrelor, and ASA plus ticagrelor was lacking, while ASA plus low-dose rivaroxaban was more effective in preventing MACE (RR 0.87, 95% CI 0.78-0.97) and MALE (RR 0.89, 95% CI 0.81-0.97) compared to ASA. ASA plus clopidogrel was not superior to ASA in preventing MACE ≥ 3 months after revascularization. Evidence regarding antithrombotic treatment strategies within 3 months after a peripheral intervention was lacking.. Clopidogrel, ticagrelor, ASA plus ticagrelor, and ASA plus low-dose rivaroxaban are superior to ASA monotherapy and equally effective to one another in preventing MACE in PAD. Of these four therapies, only ASA plus low-dose rivaroxaban provides a higher risk of major bleedings. More than 3 months after peripheral vascular intervention, ASA plus low-dose rivaroxaban is superior in preventing MACE and MALE compared to ASA but again at the cost of a higher risk of bleeding, while other treatment regimens show non-superiority. Based on the current evidence, clopidogrel may be considered the antithrombotic therapy of choice for most PAD patients, while in patients who underwent a peripheral vascular intervention, ASA plus low-dose rivaroxaban could be considered for the long-term (> 3 months) prevention of MACE and MALE.

Topics: Aspirin; Clopidogrel; Fibrinolytic Agents; Hemorrhage; Humans; Network Meta-Analysis; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Ticagrelor; Vitamin K

Antiplatelet therapy is key to prevent recurrences in patients with an acute or prior non-cardioembolic stroke or transient ischemic attack (TIA). The narrow balance between the risks of ischemic recurrence and major bleeding is a relevant clinical dilemma in this population.. This review covers the current evidence on antiplatelet therapy for patients with non-cardioembolic stroke or TIA. Randomized controlled trials of antithrombotic strategies for patients with these conditions were searched in Pubmed/Medline from 1970 to 2022.. Numerous randomized controlled trials have defined the current indications to the use of antiplatelet drugs for patients with non-cardioembolic ischemic stroke or TIA. For the management of these subjects, single antiplatelet therapy with aspirin or clopidogrel, or the combination of aspirin and dipyridamole, is usually recommended. After an acute stroke or TIA, a short course of dual antiplatelet therapy with aspirin in combination with clopidogrel or ticagrelor should be considered. The risk of bleeding might be higher with ticagrelor, but a direct comparison with clopidogrel is not available in this setting. The introduction of newer strategies, such as dual-pathway inhibition with aspirin and a direct oral anticoagulant (including emerging factor XI inhibitors under clinical development) may open a new research avenue in this challenging area.

Topics: Anticoagulants; Aspirin; Clopidogrel; Dipyridamole; Drug Therapy, Combination; Factor XI; Fibrinolytic Agents; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Stroke; Ticagrelor

This systematic review and meta-analysis evaluates the safety and efficacy of dual antiplatelet therapy (DAPT) in elderly patients with acute coronary syndrome (ACS).. The safety and efficacy of DAPT in elderly patients with ACS is not well characterized.. We performed a systematic literature review to identify clinical studies that reported safety and efficacy outcomes after DAPT for ACS in elderly patients. The primary outcomes of primary efficacy endpoint rates and bleeding event rates were reported as random effects risk ratio (RR) with 95% confidence interval. No prior ethical approval was required since all data are public.. This systematic review and meta-analysis suggests that DAPT with prasugrel or ticagrelor compared to clopidogrel is associated with a higher risk of bleeding events in elderly patients with ACS. There was no difference in the primary efficacy endpoints between the two treatment groups.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Assessment; Ticagrelor; Treatment Outcome

The benefit of using antiplatelet monotherapy in acute ischemic stroke and secondary stroke prevention is well established. In the last few years, several large randomized trials showed that the use of short-term dual antiplatelet therapy in particular stroke subtypes may reduce the risk of recurrent ischemic events. The aim of this article is to provide a critical analysis of the current evidence and recommendations for the use of antiplatelet agents for stroke prevention.. Long-term therapy with aspirin, clopidogrel, or aspirin plus extended-release dipyridamole is recommended for secondary stroke prevention in patients with noncardioembolic ischemic stroke. Short-term dual antiplatelet therapy with aspirin and clopidogrel is superior to antiplatelet monotherapy in secondary stroke prevention when used in patients with mild noncardioembolic stroke or high-risk transient ischemic attack. Dual therapy, however, is associated with an increased risk of major bleeding, particularly when the treatment is extended for greater than 30 days. Similarly, aspirin plus ticagrelor is superior to aspirin monotherapy for the prevention of recurrent ischemic stroke, although this combination is associated with a higher risk of hemorrhagic complications when compared to other dual antiplatelet regimens. Among patients who carry CYP2C19 genetic polymorphisms associated with a slow bioactivation of clopidogrel, short-term treatment with aspirin plus ticagrelor is superior to aspirin plus clopidogrel for the reduction of recurrent stroke; however, the use of ticagrelor is associated with a higher risk of any bleeding. In patients with symptomatic intracranial stenosis, aggressive medical management in addition to dual antiplatelet therapy up to 90 days is recommended. Antiplatelet therapy has an essential role in the management of ischemic stroke. The specific antiplatelet regimen should be individualized based on the stroke characteristics, time from symptom onset, and patient-specific predisposition to develop hemorrhagic complications.

Topics: Aspirin; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Ischemic Stroke; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Ticlopidine

The role of P2Y12 inhibition in acute coronary syndrome (ACS) has been well described in literature. However, the agent of choice is less clear among elderly patients (>65 years) who are at increased risk of bleeding. This meta-analysis was designed to investigate the efficacy and safety of potent P2Y12 inhibitors vs. clopidogrel in this population.. PubMed, Cochrane Central Register of Clinical Trials, EMBASE, and ClinicalTrial.gov (inception through February 25, 2021) were searched for randomized studies comparing potent oral P2Y12 inhibitors to clopidogrel in elderly population presenting with ACS. Study endpoints included major adverse cardiac events (MACE), major bleeding, all-cause mortality, cardiovascular mortality, myocardial infarction, and stroke. Hazard ratios (HRs) with 95% confidence intervals (CIs) were computed and p<0.05 was considered significant. Eight randomized studies with a total 10,081 patients were included in the final analysis. At mean follow up of 26 months, there were no significant differences between potent oral P2Y12 inhibitors and clopidogrel in MACE (HR 0.97, 95% CI [0.82-1.15]; p=0.73), all-cause mortality (HR 0.91, 95% CI [0.75-1.10]; p=1.00), MI (HR 0.95, 95% CI [0.78-1.17]; p=0.64), and stroke (HR 1.24, 95% CI [0.82-1.86]; p=0.31). However, potent oral P2Y. In comparison with clopidogrel, the use of potent oral P2Y12 inhibitors in elderly patients with ACS, is associated with a reduction in the risk of cardiovascular mortality with increased risk of bleeding events and no significant change in MACE outcomes.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Stroke; Ticagrelor; Treatment Outcome

Antiplatelet therapy is the cornerstone for acute ischemic stroke or transient ischemic attack (TIA). The purpose of this study was to conduct a meta-analysis to assess the efficacy and safety of P2Y12 receptor inhibitor plus aspirin versus aspirin alone treated within 24 h after acute noncardioembolic ischemic stroke or TIA.. We search Pubmed, EMBASE, CENTRAL and clinicaltrials.gov from January 1966 to January 2021. We included randomized trials which compared P2Y12 receptor inhibitor plus aspirin versus aspirin alone. Relative risk (RR) with 95% confidence (CI) was used as a measure of P2Y12 receptor inhibitor plus aspirin versus aspirin. The primary efficacy endpoint was recurrent stroke and the primary safety endpoint was severe bleeding.. The search identified 5 randomized trials comparing P2Y12 receptor inhibitor plus aspirin and aspirin with 21,808 individuals enrolled. Pooled results from these trials showed that P2Y12 receptor inhibitor plus aspirin compared with aspirin was associated with a lower risk of recurrent stroke (RR 0.75, 95% CI 0.68 to 0.83). Ticagrelor plus aspirin compared with aspirin was associated with increased risk of severe bleeding (RR 3.98, 95% CI 1.74 to 9.10) and intracranial hemorrhage (RR 3.32, 95% CI 1.33 to 8.25), whereas clopidogrel plus aspirin vs. aspirin had similar hemorrhagic risk.. P2Y12 receptor inhibitor plus aspirin vs aspirin given within 24 h after acute noncardioembolic ischemic stroke or TIA reduces the risk of subsequent stroke. However, the risk of severe bleeding, including intracranial hemorrhage, was higher with ticagrelor plus aspirin vs aspirin.. CRD42020203730.

Topics: Aspirin; Cerebral Infarction; Drug Therapy, Combination; Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Stroke; Ticagrelor

Bleeding is an untoward outcome in the management of elderly patients with acute coronary syndrome (ACS). Although the potent oral P2Y12 inhibitor, ticagrelor is clinically beneficial, its association with bleeding events in elderly ACS patients (≥75 years) is poorly understood.. We conducted a systematic search of 7 databases up to May 20, 2020 to identify studies which examined the risk of bleeding (defined according to each study) among elderly ACS patients (≥75 years) receiving ticagrelor compared to clopidogrel. Summary risk ratios (RR) were estimated using the random effects model.. Eight studies consisting of 5 observational studies and 3 randomized controlled trials involving 7032 elderly patients met the eligibility criteria. The mean age of the patients was 77.8 years, and the mean follow-up duration was 12 months. Overall, the pooled RRs showed higher risk of a bleeding event with ticagrelor compared to clopidogrel (RR 1.20, 95% confidence interval [95% CI] 1.03-1.40; P = .017). No statistically significant heterogeneity was observed among the studies (Q = 6.93; P = .44; I2 = 0). Also, pooled RRs did not show a higher risk of major bleeding (RR 1.32, 95% CI 0.91-1.92; P = .15) or minor bleeding (RR 1.09, 95% CI 0.76-1.58; P = .64) when comparing the ticagrelor to the clopidogrel group.. There is a 20% increased risk of a bleeding event in elderly ACS patients treated with ticagrelor compared to clopidogrel; for such patients, clopidogrel may be considered as an alternative agent to ticagrelor due to its lower risk of bleeding.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Saudi Arabia; Ticagrelor; Treatment Outcome

Very early (1-3 months) discontinuation of dual antiplatelet therapy (DAPT) has been recently proposed in percutaneous coronary interventions with modern drug-eluting stents (DES), with contrasting results. The aim of the present meta-analysis was to evaluate the prognostic impact of very short DAPT regimens vs the standard 12-month regimen in patients undergoing percutaneous coronary intervention with new DES.. Literature and main scientific session abstracts were searched for randomized clinical trials (RCT). The primary efficacy endpoint was mortality, and the primary safety endpoint was major bleeding events. A prespecified analysis was conducted according to the long-term antiplatelet agent.. We included 5 RCTs, with a total of 30 621 patients; 49.97% were randomized to very short (1-3 months) DAPT, followed by aspirin or P2Y. Based on the current meta-analysis, a very short (1-3 months) period is associated with a significant reduction in major bleeding compared with the standard 12-month therapy, with no increase in major ischemic events and comparable survival.

Topics: Aspirin; Clopidogrel; Drug Therapy, Combination; Drug-Eluting Stents; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Ticagrelor; Time Factors; Treatment Outcome

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Clopidogrel; Dual Anti-Platelet Therapy; Female; Glomerular Filtration Rate; Hemorrhage; Humans; Male; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Ticagrelor

Dual antiplatelet therapy (DAPT) with aspirin and ticagrelor or prasugrel is the mainstay of treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We aimed to systematically perform a head-to-head comparison of ticagrelor vs prasugrel in terms of efficacy and safety.. We searched PubMed/Medline, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) for relevant published randomized controlled trials (RCTs). The primary outcome was adverse cardiovascular events and secondary outcome was bleeding events. A random-effects meta-analysis was used to obtain the pooled estimate of each outcome.. Nine RCTs with a total number of 6990 patients (3550 treated with prasugrel and 3481 treated with ticagrelor) were included. No significant difference between prasugrel and ticagrelor was observed in terms of mortality (OR 0.86, 95% CI 0.66 to 1.13, P = 0.28), major adverse cardiovascular events (MACEs) (OR 0.85, 95% CI 0.70 to 1.03, P = 0.10), non-fatal myocardial infarction (OR 0.78, 95% CI 0.57 to 1.06, P = 0.11), stroke (OR 1.02, 95% CI 0.60 to 1.72, P = 0.95), stent thrombosis (OR 0.76, 95% CI 0.47 to 1.21, P = 0.25), thrombolysis in myocardial infarction (TIMI) defined major (OR 0.94, 95% CI 0.19 to 4.67, P = 0.94), minor (OR 0.35, 95% CI 0.08 to 1.62, P = 0.18) and minimal (OR 0.48, 95% CI 0.19 to 1.18, P = 0.11) bleeding and Bleeding Academic Research Consortium (BARC) defined bleeding (OR 1.06, 95% CI 0.82 to 1.36, P = 0.68).. In patients with ACS undergoing PCI, both prasugrel and ticagrelor were associated with similar cardiovascular outcomes and adverse bleeding events.

Topics: Acute Coronary Syndrome; Aspirin; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Ticagrelor

Ticagrelor has been shown to offer potential outcome benefits in acute coronary syndromes and for the long-term cardiovascular prevention, reducing mortality and the recurrence of ischemic events. However, data from real-world and recent meta-analyses have suggested that the anti-ischemic benefits of ticagrelor could be lower than expected, potentially outweighed by an increased risk of bleeding complications. Therefore, the aim of the present meta-analysis was to evaluate the prognostic impact of ticagrelor as compared to the conventional antiplatelet agents (ASA and clopidogrel) in patients with coronary artery disease (CAD), enclosing patients with acute coronary syndromes and stable CAD.. Literature and main scientific session abstracts were searched for studies comparing a ticagrelor-based antiplatelet regimen vs different antiplatelet agents in patients with CAD. The primary efficacy endpoint was mortality, and the primary safety endpoint was the occurrence of major bleedings. Secondary endpoints were cardiovascular mortality, myocardial infarction, stroke and intracranial hemorrhage (ICH).. We included 15 randomized clinical trials, with a total population of 73,402 patients (55% randomized to ticagrelor). At a mean follow-up of 15 ± 11.3 months, the ticagrelor based strategy did not significantly reduce mortality as compared to the traditional therapy (OR[95%CI] = 0.88[0.70,1.09], p = 0.24; phet<0.00001), with comparable results and no interaction according to patients' presentation (p interaction = 0.80). A similar result was achieved for cardiovascular mortality, whereas the reduction of recurrent myocardial infarction was significant (OR[95%CI] = 0.84[0.78,0.90], p < 0.00001; phet = 0.76). As for the risk of stroke, the largest reduction was observed in stable patients, while a neutral effect was observed in the ACS subgroup (p int = 0.35). Major bleeding events were increased in ticagrelor-treated patients (OR [95%CI] = 1.40 [1.06, 1.84], p = 0.02; phet<0.00001), especially ICH (OR [95% CI] = 1.45[1.13,1.84], p = 0.003; phet = 0.93), and mainly among non-ACS patient. No interaction for any outcome endpoint was observed according to patients' age.. Based on the current meta-analysis, a ticagrelor-based strategy for the treatment of patients with coronary artery disease is associated to a significant increase in major bleeding complications and especially for intracranial hemorrhage, as compared to a strategy based on conventional antiplatelet agents, while resulting in a neutral effect on survival. However, a significant reduction of recurrent myocardial infarction was observed with ticagrelor.

Topics: Acute Coronary Syndrome; Coronary Artery Disease; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Recurrence; Risk Assessment; Risk Factors; Ticagrelor; Treatment Outcome

Dual antiplatelet therapy (DAPT) and subsequent P2Y

Topics: Acute Coronary Syndrome; Cardiovascular Diseases; Drug Therapy, Combination; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

Dual antiplatelet treatment, consisting of aspirin and P2Y12 inhibitors, is essential for diabetes mellitus (DM) patients who have undergone percutaneous coronary intervention (PCI). This meta-analysis investigated whether ticagrelor, a novel P2Y12 inhibitor, was superior to clopidogrel and prasugrel in efficacy and safety for DM patients undergoing PCI. PubMed, the Cochrane Library and Google Scholar were searched for randomized controlled trials in which ticagrelor was administered. Eligible studies were independently scrutinized to extract data and assess the trials' quality. Statistical analysis was performed by calculating odds ratios (OR) and 95% confidence intervals (CI). A total of 8 studies consisting of 1056 patients were included. Results showed that ticagrelor reduced the major adverse cardiac events incidence compared with clopidogrel and prasugrel in the overall (OR = 0.40; 95% CI, 0.20-0.79; P = 0.008) and subgroup analyses compared with clopidogrel (OR = 0.39; 95% CI, 0.19-0.80; P = 0.01). No difference was observed in mortality rates (OR = 0.58; 95% CI, 0.23-1.45; P = 0.25), myocardial infarction (OR = 0.67; 95% CI, 0.28-1.60; P = 0.37), stroke (OR = 0.54; 95% CI, 0.10-3.01; P = 0.49), and total bleeding (OR = 1.70; 95% CI, 0.91-3.17; P = 0.10) between the ticagrelor and control groups. In DM patients undergoing PCI, ticagrelor significantly reduced major adverse cardiac events compared with clopidogrel and prasugrel in the overall and in the subgroup of clopidogrel. There was no difference regarding mortality, myocardial infarction, stroke, and bleeding. More randomized controlled trials are required to further validate these results.

Topics: Coronary Artery Disease; Diabetes Mellitus; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Stroke; Ticagrelor; Time Factors; Treatment Outcome

Whether guided selection of antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) is effective in improving outcomes compared with standard antiplatelet therapy remains controversial. We assessed the safety and efficacy of guided versus standard selection of antiplatelet therapy in patients undergoing PCI.. For this systematic review and meta-analysis, from Aug 20 to Oct 25, 2020, we searched MEDLINE (via PubMed), Cochrane, Embase, and Web of Science databases for randomised controlled trials and observational studies published in any language that compared guided antiplatelet therapy, by means of platelet function testing or genetic testing, versus standard antiplatelet therapy in patients undergoing PCI. Two reviewers independently assessed study eligibility, extracted the data, and assessed risk of bias. Risk ratios (RRs) and 95% CIs were used with random-effects or fixed-effect models according to the estimated heterogeneity among studies assessed by the I. 3656 potentially relevant articles were screened. Our analysis included 11 randomised controlled trials and three observational studies with data for 20 743 patients. Compared with standard therapy, guided selection of antiplatelet therapy was associated with a reduction in major adverse cardiovascular events (RR 0·78, 95% CI 0·63-0·95, p=0·015) and reduced bleeding, although not statistically significant (RR 0·88, 0·77-1·01, p=0·069). Cardiovascular death (RR 0·77, 95% CI 0·59-1·00, p=0·049), myocardial infarction (RR 0·76, 0·60-0·96, p=0·021), stent thrombosis (RR 0·64, 0·46-0·89, p=0·011), stroke (RR 0·66, 0·48-0·91, p=0·010), and minor bleeding (RR 0·78, 0·67-0·92, p=0·0030) were reduced with guided therapy compared with standard therapy. Risks of all-cause death and major bleeding did not differ between guided and standard approaches. Outcomes varied according to the strategy used, with an escalation approach associated with a significant reduction in ischaemic events without any trade-off in safety, and a de-escalation approach associated with a significant reduction in bleeding, without any trade-off in efficacy.. Guided selection of antiplatelet therapy improved both composite and individual efficacy outcomes with a favourable safety profile, driven by a reduction in minor bleeding, supporting the use of platelet function or genetic testing to optimise the choice of agent in patients undergoing PCI.. None.

Topics: Acute Coronary Syndrome; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Stroke; Ticagrelor

Patients with minor ischemic stroke or transient ischemic attack represent a high-risk population for recurrent stroke. No direct comparison exists comparing dual antiplatelet therapy regimens-namely, Ticagrelor and Aspirin versus Clopidogrel and Aspirin. This systematic review and network meta-analysis (NMA) will examine the efficacy of these two different antiplatelet regimens in preventing recurrent stroke and mortality up to 30 days.. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched with the assistance of a medical information specialist. Two independent reviewers will screen studies for inclusion; eligible studies will include randomized controlled trials that enrolled adults presenting with acute minor ischemic stroke or transient ischemic attack and compared one or more of the interventions against each other and/or a control. The primary outcomes will be recurrent ischemic stroke up to 30 days from symptom onset. Secondary outcomes will include safety outcomes (I.e. major bleeding and mortality), functional disability, and outcomes up to 90 days from symptom onset. A Bayesian approach to NMA will be implemented using the BUGSnet function in R Software. Between group comparisons for time-to-event (TTE) and dichotomous outcomes will be presented in terms of hazard ratios and odds ratios with 95% credible intervals, respectively. Secondary effect measures of treatment ranking will also be estimated.. No formal research ethics approval are necessary. We will disseminate our findings through scientific conference presentations, peer-reviewed publications, and social media/the press. The findings from this review will aid clinicians in decision-making on the choice of antithrombotic therapy in a high-risk stroke population and could be important in the development of future treatment trials and guidelines. Registration ID with Open Science Framework: 10.17605/OSF.IO/XDJYZ.

Topics: Aspirin; Bayes Theorem; Brain Ischemia; Clopidogrel; Drug Therapy, Combination; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Network Meta-Analysis; Platelet Aggregation Inhibitors; Ticagrelor

Antiplatelet medications are the mainstay for secondary stroke treatment. Aspirin, clopidogrel, and aspirin-dipyridamole are commonly used antiplatelet medications. Other antiplatelet medications such as ticagrelor and prasugrel have been majorly used in cardiovascular or neuro-interventional specialties. Recent studies have paved a way to their use in secondary stroke prevention. In this review, we have briefly discussed the pharmacology of ticagrelor, published literature in cardiology and stroke trials, use of ticagrelor among patients with ischemic strokes, and compared its efficacy, limitations and side-effects with other antiplatelet medications.

Topics: Hemorrhage; Humans; Ischemic Stroke; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Secondary Prevention; Ticagrelor; Treatment Outcome

The efficacy of early administration of dual antiplatelet therapy (DAPT) for secondary prevention after acute ischemic stroke or transient ischemic attack (TIA) is uncertain. This systematic review and meta-analysis compares the safety and efficacy of early administration (<24 hours) of DAPT (using either clopidogrel or ticagrelor with aspirin) versus single antiplatelet therapy (SAPT; aspirin alone) in acute non-cardioembolic ischemic stroke or TIA, incorporating data from large randomized controlled trials. Published trials fulfilling our criteria were identified from an electronic search of MEDLINE, with key words including: "clopidogrel or ticagrelor", "aspirin", "ischemic stroke", "transient ischemic attack", and "randomized controlled trial". Included were 3 randomized controlled trials of 21,067 patients assessing early administration (<24 hours from symptom onset) of DAPT versus SAPT in non-cardioembolic acute ischemic stroke or TIA. Our efficacy outcomes were ischemic stroke and all-cause mortality. Our safety outcome was severe bleeding. We performed a meta-analysis to pool results with a hierarchical Bayesian random-effects model. Dual antiplatelet therapy significantly reduced the risk of ischemic stroke (hazard ratio [HR], 0.73; 95% credible interval [CrI]: 0.54, 0.97), while increasing the risk of severe bleeding (HR, 2.48; 95% CrI: 1.07, 5.26). There was a non-significant numerical trend toward increased mortality with DAPT (HR, 1.29; 95% CrI: 0.73, 2.23). These observations were robust under the sensitivity analysis. In the present systematic review and meta-analysis of randomized controlled trials, DAPT reduced the risk of ischemic stroke at the cost of an increase in severe bleeding. Additional trials examining the ideal timing of DAPT administration are needed to thoroughly investigate the role, if any, of routine DAPT in patients with non-cardioembolic ischemic stroke or high-risk TIA.

Topics: Aspirin; Clopidogrel; Dual Anti-Platelet Therapy; Early Medical Intervention; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Mortality; Platelet Aggregation Inhibitors; Proportional Hazards Models; Secondary Prevention; Ticagrelor

Randomized trials did not consistently support superiority of ticagrelor, as monotherapy or in combination with aspirin, in terms of efficacy or safety, in patients with atherosclerotic artery disease.. Medline, EMBASE, the Cochrane Central Register of Controlled Trials, and scientific session abstracts were searched for trials of patients with coronary or peripheral artery disease (with >1,000 participants and a follow-up ≥3 months) randomly assigned to ticagrelor-based or conventional antiplatelet therapies. Trial-level hazard ratios (HRs) were pooled using a fixed- or random-effect model (in case of significant heterogeneity) with the inverse variance weighting. The primary outcome was all-cause mortality. Other outcomes were myocardial infarction (MI), stroke, and major bleeding.. Overall 77,489 patients received either ticagrelor-based (n = 38,721) or conventional antiplatelet regimens (n = 38,768) in 6 trials. The primary outcome occurred in 4.5% of patients treated with experimental therapy and 4.9% of patients treated with control therapy (HR = 0.91, 95% CI 0.81-1.01; P = .07). Overall, patients treated with ticagrelor-based versus conventional antiplatelet regimens showed no significant difference in terms of all-cause death, MI, stroke, or major bleeding after 20 months. However, in trials of patients with coronary artery disease as primary diagnosis, the risk for all-cause death (HR = 0.84 [0.77-0.91], P < .001) and MI (HR = 0.87 [0.80-0.94], P = .007) was significantly reduced by experimental therapy.. In patients with atherosclerotic artery disease, the benefit of ticagrelor-based therapies was confined to patients treated for coronary artery disease. The drug significantly reduced the risk for all-cause death and MI without excess risk of bleeding in these patients. In consideration of limitations of subgroup analyses, these results need further validation.

Topics: Atherosclerosis; Cause of Death; Coronary Artery Disease; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Stroke; Ticagrelor

The optimal antithrombotic strategy for patients with a long-term indication for anticoagulation and acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) remains controversial. This meta-analysis aims to compare randomised trials' outcomes of these patients, focussing on dual versus triple antithrombotic and non vitamin K oral anticoagulants (NOACs) versus vitamin K oral anticoagulants regimens.. Medline, Embase and Cochrane databases were searched from January 1980 to March 2019 yielding 309 articles, and after careful screening, five randomized trials totalling 10 643 patients were included for analysis.. Dual antithrombotic regimens were associated with significantly less thrombolysis in myocardial infarction (TIMI) major and minor bleeding [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.40-0.71], with no significant difference in major adverse cardiovascular events (OR 0.93, 95% CI 0.72-1.22) or all-cause mortality (OR 0.89, 95% CI 0.61-1.19). NOAC regimens had significantly lower TIMI major and minor bleeding (OR 0.58, 95% CI 0.43-0.78) and intracranial bleeding (OR 0.33, 95% CI 0.16-0.66), with similar rates of major adverse cardiovascular events (OR 1.00, 95% CI 0.86-1.16) and all-cause mortality (OR 1.01, 95% CI 0.81-1.26).. Dual antithrombotic and NOAC regimens have reduced bleeding without compromising the risk of cardiovascular events or mortality, and should be preferred for patients with ACS or PCI also needing long-term anticoagulation.

Topics: Acute Coronary Syndrome; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Dabigatran; Drug Therapy, Combination; Dual Anti-Platelet Therapy; Factor Xa Inhibitors; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Stroke; Ticagrelor; Warfarin

Antiplatelet therapy, the cornerstone of post coronary stenting antithrombotic therapy, reduces the rate of hard clinical endpoints in patients treated both conservatively and invasively following an acute coronary syndrome, as well as in those patients with chronic stable coronary disease who receive a coronary stent. The development of newer antiplatelet and direct anticoagulant agents provides new options in the antithrombotic management of patients with coronary artery disease, enabling different therapeutic combinations to be tailored to an individual patient's bleeding and ischemic risk profile. In this review, we will summarize the history of dual antiplatelet therapy, discuss the latest evidence and future perspectives in treating patients with coronary artery disease.

Topics: Acute Coronary Syndrome; Anticoagulants; Clopidogrel; Coronary Artery Disease; Drug-Eluting Stents; Dual Anti-Platelet Therapy; Heart Diseases; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Risk Assessment; Ticagrelor

Although current guidelines recommend ticagrelor in addition to aspirin as the antiplatelet strategy for medically managed acute coronary syndrome (MMACS) patients, clinical evidence specific to this special population is lacking. Whether potent oral P2Y. We conducted a comprehensive search in PubMed, Embase, Web of Science, and Cochrane Library to identify studies exploring the efficacy or safety of ticagrelor and prasugrel versus clopidogrel or placebo in MMACS patients. The primary efficacy endpoint was major adverse cardiovascular events (MACE) defined by each study, and the safety endpoint was TIMI non-CABG major bleeding.. A total of 6102 records were screened, and 4 studies including 46,346 patients were finally included. The use of potent oral P2Y. Potent oral P2Y

Topics: Acute Coronary Syndrome; Administration, Oral; Aged; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

The databases PubMed, Embase, and Cochrane's Library were systematically searched for relevant randomized controlled trials concerning prasugrel or ticagrelor (test) relative to clopidogrel (control). Depending on heterogeneity, studies were pooled with a random effects or a fixed effects model. Outcomes of blood flow after PCI were evaluated, including TIMI (thrombolysis in myocardial infarction), bleeding events, and major adverse cardiovascular events (MACEs).. Seven studies comprising 11,874 patients conformed to the inclusion criteria. The pooled results with the fixed effects model indicated that after PCI patients in the prasugrel or ticagrelor groups were as likely as those treated with clopidogrel to achieve TIMI grade 3 flow or experience bleeding events. However, compared with the control, the test groups had significantly less risk of MACE (OR: 0.81, 95% CI: 0.70-0.94, P = 0.004), especially at the 1-year follow-up (OR: 0.79, 95% CI: 0.66-0.95, P = 0.01).. A prasugrel- or ticagrelor-based TAPT may reduce the rate of MACEs, without increasing bleeding in STEMI patients undergoing PCI. However, due to the limited RCT studies and variations in study weight, results of this meta-analysis should be confirmed in a large RCT with adequate sample size and follow-up duration.

Topics: Aged; Aged, 80 and over; Clopidogrel; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Recurrence; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Dual antiplatelet therapy combining aspirin with a P2Y

Topics: Acute Coronary Syndrome; Aspirin; Cause of Death; Clopidogrel; Graft Occlusion, Vascular; Hemorrhage; Humans; Myocardial Infarction; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Stents; Ticagrelor

Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y. In this systematic review and meta-analysis, all randomised trials comparing P2Y. A total of nine randomised trials were identified and included in this study, and 42 108 patients randomly allocated to a P2Y. Compared with aspirin monotherapy, P2Y. Italian Ministry of Education.

Topics: Aged; Aspirin; Atherosclerosis; Cerebrovascular Disorders; Clopidogrel; Coronary Disease; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Assessment; Secondary Prevention; Stroke; Ticagrelor; Ticlopidine

Dual antiplatelet therapy with aspirin and a P2Y. A meta-analysis was conducted from randomized trials (2001-2020) that studied discontinuation of aspirin 1 to 3 months after PCI with continued P2Y. The study population included 32 145 patients: 14 095 (43.8%) with stable coronary artery disease and 18 046 (56.1%) with acute coronary syndrome. In the experimental arm, background use of a P2Y. Discontinuation of aspirin with continued P2Y

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Percutaneous Coronary Intervention; Postoperative Complications; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Ticagrelor; Withholding Treatment

Ticagrelor is an antiplatelet agent acting through direct and reversible competitive inhibition of the platelet P2Y. This review aims to inform about recent findings on ticagrelor, by appraising the current body of evidence on its use in different clinical scenarios, particularly in DM, ranging from pharmacology to clinical outcomes and future directions.. The results of the THEMIS trial, conducted in DM patients with stable coronary artery disease and no prior stroke or myocardial infarction, showed that although ticagrelor in addition to aspirin reduced the risk of ischemic events, this was associated with a parallel increase in bleeding complications. However, patients with history of percutaneous coronary intervention seemed to benefit more from adjunctive ticagrelor therapy. Careful bleeding and ischemic risk stratification remains crucial to define the best antithrombotic strategy for the individual patient.

Topics: Aspirin; Clinical Trials as Topic; Coronary Artery Disease; Diabetes Complications; Drug Therapy, Combination; Hemorrhage; Humans; Myocardial Ischemia; Platelet Aggregation Inhibitors; Ticagrelor

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y. A search of PubMed was performed to identify articles published in the last 20 years that addressed the role of DAPT beyond 12 months' duration.. A number of studies have shown ischemic benefits associated with prolonging DAPT beyond 12 months, but this finding is dependent on the patient population studied and the quality of the study design. Many studies also show that longer duration therapy has been associated with increased bleeding risk. In patients with previous myocardial infarction completing at least 1 year of DAPT, continuing DAPT with a reduced dose of ticagrelor 60 mg BID is a regimen to be considered for these patients; in general ACS patients, a reduced dose of 60 mg BID of ticagrelor after the first year of DAPT should be considered; and in the post-percutaneous coronary intervention patients, DAPT beyond 1 year should be considered after careful evaluation of the patient's thrombotic and bleeding risks.. The duration of DAPT, and the choice of P2Y

Topics: Acute Coronary Syndrome; Aspirin; Drug Therapy, Combination; Drug-Eluting Stents; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Secondary Prevention; Thrombosis; Ticagrelor; Time Factors

Traditionally, aspirin has played a significant role in both primary and secondary prevention of cardiovascular disease. However, emerging antithrombotic regimens with better efficacy and safety have challenged the foundation of aspirin. Aspirin-free strategies consisting of P2Y12 inhibitor monotherapy following percutaneous coronary intervention (PCI) have now been tested in several large randomized controlled trials. In this article, we provide a contemporary overview of these data and suggest an algorithm to inform clinical decision with respect to antiplatelet pharmacotherapy after PCI.

Topics: Aspirin; Clinical Trials as Topic; Coronary Artery Disease; Drug Therapy, Combination; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Secondary Prevention; Ticagrelor

Topics: Aspirin; Clopidogrel; Drug Resistance; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Risk Assessment; Secondary Prevention; Severity of Illness Index; Ticagrelor

Topics: Acute Coronary Syndrome; Clopidogrel; Coronary Artery Bypass; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Ticagrelor

There are clinical scenarios where the balance between the risk of ischemic and bleeding events leads to the clinical decision to reverse the antiplatelet effect of P2Y

Topics: Administration, Oral; Antibodies, Monoclonal; Blood Platelets; Broadly Neutralizing Antibodies; Cardiology; Clopidogrel; Hemadsorption; Hemorrhage; Hemostasis; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk; Signal Transduction; Thrombosis; Ticagrelor

Antiplatelet therapy is extensively used in the primary and secondary prophylaxis of arterial thrombotic disorders. Aspirin, the most commonly used antiplatelet agent, is a cyclooxygenase-1 inhibitor and considered a mild to moderate inhibitor of platelet function. Therefore, often a second antiplatelet agent is necessary in certain clinical conditions requiring greater inhibition of platelet function. An adenosine diphosphate (ADP) receptor, P2Y12, is an important target for this purpose; several agents inhibit this receptor providing potent antiplatelet effect. One of the side effects of these agents is bleeding, which in some patients may require reversal of antiplatelet effect. Similarly, patients undergoing emergent surgeries may benefit from reversal of antiplatelet effect to avoid excessive surgical bleeding. This article reviews current literature on this topic.

Topics: Aspirin; Blood Loss, Surgical; Blood Platelets; Cyclooxygenase Inhibitors; Hemorrhage; Hemostasis; Humans; Phosphodiesterase Inhibitors; Platelet Aggregation Inhibitors; Platelet Function Tests; Platelet Transfusion; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Thromboembolism; Ticagrelor

Early administration of P2Y12-receptor inhibitors is recommended in all patients with acute coronary syndrome undergoing invasive management, with the aim to achieve the fastest and most effective platelet inhibition. Several trials investigated alternative methods of P2Y12-receptor inhibitor administration (mainly chewed or crushed) aimed at ensuring faster and higher platelet inhibition. Thus, we decided to perform a systematic review and meta-analysis analyzing efficacy and safety of alternative P2Y12-receptor inhibitor administration strategies.. Systematic research was performed on Pubmed, Cochrane Library, Biomed Central, and Web of Science databases. We included randomized or observational trials testing at least one P2Y12-receptor inhibitor alternative administration. The primary outcome of the study was the value of the platelet reactivity unit (PRU) at 1 h after drug administration, assessed by VerifyNow P2Y12 test (Accumetrics, Inc., San Diego, CA). Secondary outcomes were adverse bleeding events (safety outcome).. Fourteen studies were selected for qualitative analysis. Five studies, all focused on ticagrelor, were selected for quantitative efficacy analyses. These five studies compared the administration of crushed/chewed ticagrelor 180 mg loading dose (LD) with the standard whole tablets LD. The pooled mean difference between the two administrations was -59.24 PRU (95% CI from -30.61 to -87.87 PRU) in favor of the crushed/chewed administration, corresponding to a 25% mean relative PRU reduction between alternative and standard P2Y12-receptor inhibitor administrations at 1 h after drug intake. A similar relationship was found in other studies on alternative administration of clopidogrel and prasugrel, not included in the quantitative analysis.

Topics: Acute Coronary Syndrome; Administration, Oral; Clopidogrel; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Safety; Ticagrelor; Treatment Outcome

Background As reports on the influence of cigarette smoking, an important cardiovascular risk factor, on platelet ADP -P2Y12 receptor inhibitors lack consistency, we aimed to assess the effectiveness and safety of platelet ADP -P2Y12 receptor inhibitors influenced by smoking status. Methods and Results PubMed, Web of Science, EMBASE , Clinical Trials, and the Cochrane Library were searched from inception until June 2018. Among the 5076 citations retrieved, 22 studies, including 163 011 patients with or without percutaneous coronary intervention, were included for meta-analysis. Compared with nonsmokers within the first year of follow-up, the reductions of stroke and major adverse cardiovascular event rate were 18% ( P=0.008) and 26% ( P=0.02), respectively. A 20% reduction in stroke ( P=0.02) and a 34% reduction in major adverse cardiovascular event ( P=0.0001) rates were observed in smoking patients without percutaneous coronary intervention. No significant difference was observed in clinical outcome rates among prasugrel, ticagrelor, and clopidogrel in different smoking status. No significant difference was found in myocardial infarction and bleeding event incidence between current smokers and nonsmokers. Conclusions We concluded that current smokers had a lower incidence of major adverse cardiovascular events and stroke events than did nonsmokers, particularly in the early period (1 year) and among patients without percutaneous coronary intervention. However, because of the lack of original adjusted data, smoker's paradox still needs to consider the impact of age and other covariates. Thus, a differential risk-benefit evaluation should be considered, according to different smoking status, patient conditions, and therapy time points.

Topics: Acute Coronary Syndrome; Aged; Cardiovascular Diseases; Cigarette Smoking; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Stroke; Ticagrelor; Treatment Outcome

In the review, we briefly describe antithrombotic drugs and the use evidence from evidence-based medicine to elucidate the optimal antithrombotic management for patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary stenting (PCI) at high risk of bleeding.. Mandatory use of intravenous anticoagulants and dual antiplatelet agents is the cornerstone strategy in acute and long-term antithrombotic management to optimize the clinical benefit of patients with STEMI undergoing PCI. Nevertheless, with the increasing occurrence of STEMI in old population with high risk of bleeding and renal insufficiency, as well as the specificity of high bleeding risk groups, the optimization of antithrombotic therapy still remains uncertain. Bivalirudin is the optimized intravenous anticoagulant agent for these patients based on the guideline recommendations and clinic data. Timely and potent ticagrelor and prasugrel with aspirin usage can increase the clinical benefit for the patients without increasing the clinical bleeding risk. At present, the multi-center, prospective clinical studies of EVOLVE short DAPT, MASTER DAPT, and POEM trials, targeting patients with high risk of bleeding, are in experimental stage. These clinical trials will provide more objective and optimal antithrombotic management strategy for the patients.

Topics: Anticoagulants; Fibrinolytic Agents; Hemorrhage; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Recombinant Proteins; ST Elevation Myocardial Infarction; Stents; Ticagrelor

De-escalation from ticagrelor to clopidogrel in acute coronary syndrome (ACS) may occur for a variety of reasons, including side effects (bleeding and non-bleeding) and costs. This study sought to assess the prevalence of de-escalation from ticagrelor to clopidogrel and the occurrence of adverse clinical outcomes following de-escalation. We conducted a systematic review of clinical trials and real-world studies in ACS patients treated with ticagrelor. Real-world data on the prevalence of de-escalation during hospitalization or at discharge, after hospital discharge, and during the whole study period were included for meta-analysis. Major adverse cardiovascular events (MACE) and bleeding events occurring after de-escalation were also assessed. A total of 12 studies were eligible for meta-analysis of the prevalence of de-escalation. De-escalation from ticagrelor to clopidogrel therapy occurred with a mean prevalence of 19.8% [95% confidence interval (CI) 11.2-28.4%]. De-escalation occurred more frequently in-hospital or at discharge than after hospital discharge (23.7% vs. 15.8%). For assessment of clinical outcomes, a total of six studies were eligible for meta-analysis. Mean rate of MACE for patients with de-escalation was 2.1% (95% CI 1.1-4.1%) and the rate of major bleeding events was 1.3% (95% CI 0.4-4.5%). In conclusion, de-escalation commonly occurs in real-world practice. Although rates of major cardiovascular and bleeding events in this analysis were generally low, the profile of patients suitable for de-escalation, the impact of de-escalation on adverse clinical outcomes and how this is affected by the timing after index ACS warrants further large-scale investigation.

Topics: Acute Coronary Syndrome; Cardiovascular Diseases; Clopidogrel; Hemorrhage; Hospitalization; Humans; Patient Discharge; Prevalence; Ticagrelor

Sickle cell disease (SCD) is the most common hemoglobinopathy, occurring worldwide, and vaso-occlusive events (VOEs) are its paramount, hallmark clinical manifestation. Evidence exists that platelets play an important role in generating VOEs.. To assess the clinical benefits and harms of antiplatelet agents for preventing VOEs in patients with SCD.. We conducted searches of the Cochrane Central Register of Controlled Trials (CENTRAL; up to 2018, issue 3 of 12), PubMed/MEDLINE (up to April 20, 2018), and the Excerpta Medica database (EMBASE; from 1980 to week 16 of 2018). We also searched the Latin American and Caribbean Health Sciences Literature (LILACS) database, the US Food and Drug Administration (FDA) website, the European Medicines Agency (EMA) website, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), and www.ClinicalTrials.gov. We checked the bibliographies of included studies and any relevant systematic reviews. Our systematic review included randomized clinical trials (RCTs) conducted in people who had SCD without VOEs at trial entry. Eligible trials compared a single or combination treatment regimen (with each treatment classified as a conventional or nonconventional antiplatelet agent) with conventional care, placebo, or another regimen. No restrictions were placed on the route of administration, dose, frequency, or duration of treatment. We selected RCTs, assessed the risk for bias, and extracted data in a duplicate and independent fashion. We estimated risk ratios for dichotomous outcomes and mean differences for continuous outcomes. We also subjected our analyses to a random-effects model, and Trial Sequential Analysis (TSA) was used. We used the grading of recommendations, assessment, development, and evaluation (GRADE) approach to assess the overall quality of data for each individual outcome.. We identified 5 RCTs (N=747) that met our criteria. Of these, 4 trials were multicenter and multinational. The trials included patients of all ages and assessed prasugrel, ticagrelor, crizanlizumab, and aspirin vs either placebo or no intervention. The most frequent route of administration was oral. The trials were small and carried a high risk for bias, given that pharmaceutical companies sponsored 4 of them. None of the trials reported information on quality of life. No meta-analysis was performed owing to heterogeneity in the ages of the participants and in the interventions. No single trial showed evidence of certainty regarding all-cause mortality. One trial showed uncertainty in comparing prasugrel vs placebo for preventing VOEs in patients younger than 18 years (relative risk [RR], 0.92; 95% CI, 0.80 to 1.06; low quality of evidence). TSA for this outcome suggested that a new trial should be conducted. One trial found a difference in the size effect of uncomplicated VOEs, favoring high-dose crizanlizumab vs placebo (mean difference, -1.50; 95% CI, -2.61 to -0.39; very low quality of evidence). No difference in VOEs was found in studies that compared either ticagrelor in children or prasugrel in adults vs placebo. The overall incidence of harms in any intervention did not differ from that in the control.. The current evidence does not support or reject the use of any antiplatelet agent for preventing VOEs in people with SCD. This conclusion was based on small RCTs that carried a high risk for bias. No conclusive evidence exists regarding relevant clinical outcomes because the evidence is limited and of very low quality.

Topics: Adult; Anemia, Sickle Cell; Antibodies, Monoclonal, Humanized; Hemorrhage; Humans; Mortality; Multicenter Studies as Topic; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Ticagrelor; Treatment Outcome; Vascular Diseases

To determine whether ticagrelor or clopidogrel provides the best outcomes for East-Asian patients with acute coronary syndrome (ACS).. Identification and interrogation of electronic databases through 26 July 2016 revealed fully randomized and controlled trials wherein primary efficacy end points were major adverse cardiovascular events and all-cause death among East-Asian patients with ACS. Major bleeding and noncoronary artery bypass grafts major bleeding were primary safety end points.. Two studies met the inclusion criteria. Compared with clopidogrel, ticagrelor has no statistical difference in the end points of major adverse cardiovascular events (risk ratio [RR]: 1.08; 95% CI: 0.62-1.91; p = 0.7260), myocardial infarction (RR: 1.200; 95% CI: 0.64-2.24; p = 0.5669), stroke (RR: 1.11; 95% CI: 0.46-2.66; p = 0.8165), cardiovascular death (RR: 0.89; 95% CI: 0.48-1.65; p = 0.7150), or all-cause mortality (RR: 0.92; 95% CI: 0.43-1.96; p = 0.8252). When compared with clopidogrel, it was found that ticagrelor provoked marked increases in major bleeding (RR: 1.48; p = 0.0430) and noncoronary artery bypass grafts-associated major bleeding (RR: 1.62; p = 0.0454).. Ticagrelor and clopidogrel displayed similar efficacies in ACS presenting patients from East Asia. Administration of ticagrelor also displays some side effects including an increased risk of major bleeding.

Topics: Acute Coronary Syndrome; Asia; Clopidogrel; Female; Hemorrhage; Humans; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Ticagrelor; Treatment Outcome

The duration and combination of dual antiplatelet therapy after coronary stent implantation, consisting of aspirin and a P2Y12 inhibitor, is among the most intensely investigated therapeutic strategies in cardiovascular medicine. While initial studies have mainly focused on the efficacy and safety of individual antithrombotic agents, the increased need for a personalized, risk-based approach to define the optimal duration of antithrombotic treatment according to the estimated ischemic and bleeding risk was then recognized. Recent recommendations for the optimal duration of antithrombotic combination therapies following coronary stent implantation in various clinical scenarios have substantially changed. The aim of the present article is to discuss the recent evidence from randomized clinical trials and observational studies with respect to antithrombotic treatment regimens in patients undergoing coronary artery stenting for stable coronary artery disease (CAD) or an acute coronary syndrome (ACS). We will focus on optimal treatment duration and a personalized approach based on ischemic and bleeding risk assessment.

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Coronary Disease; Dose-Response Relationship, Drug; Drug Therapy, Combination; Hemorrhage; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Factors; Stents; Ticagrelor

Ticagrelor is a first drug of a new chemical class cyclopentyltriazolopyrimidines. It is an antiplatelet agent with a unique mechanism of action, allowing a direct and reversible competitive inhibition of P2Y. This review is a comprehensive and thorough summary of the most important findings on ticagrelor. Pharmacokinetics, pharmacogenetics, drug-drug interactions, adverse effects, efficacy in specific patient populations and off-label properties of ticagrelor are discussed in this paper. Moreover, the results from pivotal clinical trials are presented.. Introduction of ticagrelor, a first directly-acting and reversible P2Y

Topics: Acute Coronary Syndrome; Adenosine; Cytochrome P-450 CYP2C19; Drug Interactions; Dyspnea; Half-Life; Hemorrhage; Humans; Pharmacogenetics; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor

Platelet activation plays a central role in triggering and complicating acute coronary syndromes, especially in case of stent thrombosis and myocardial infarction. On top of aspirin, P2Y12- inhibitors are successfully used to treat and prevent these events for a duration of one year after an acute coronary episode or 6 months after drug-eluting stent implantation. However, patients with acute coronary syndromes remain at heightened risk for recurrent ischemic events after the recommended durations of P2Y12-inhibitors and therefore, prolonging treatment is often considered in clinical practice. However, the higher risk for bleeding limits the utility of such approach to a restricted group who is still poorly defined by available measures. This review aims to discuss potential benefits and highlight important pitfalls of prolonged treatment with P2Y12-inhibitors, with a focus on ticagrelor, an attractive reversible P2Y12-inhibitor in patients after myocardial infarction.

Topics: Acute Coronary Syndrome; Clinical Decision-Making; Drug Administration Schedule; Drug Therapy, Combination; Drug-Eluting Stents; Hemorrhage; Humans; Patient Selection; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Recurrence; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Bleeding complications are associated with unfavorable outcomes in patients with acute coronary syndrome (ACS). Compared to Whites, several studies demonstrated a higher risk of bleeding in Asians who present with acute myocardial infarction. To date, the efficacy and safety of ticagrelor in East Asian population have not been well established.. We conducted a systematic review and meta-analysis of randomized controlled trials that compared ticagrelor and clopidogrel in East Asian patients with acute coronary syndrome (ACS). We systematically searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrial.gov database.. Three randomized controlled trials, including a total of 1552 patients, met our inclusion criteria. Study countries included Japan, South Korea, and China. All studies defined primary efficacy endpoint and major bleeding events in accordance with the PLATO definition. Ticagrelor was associated with a numerically lower, albeit statistically nonsignificant, risk of primary efficacy endpoint defined as a composite of death from vascular causes, myocardial infarction, or stroke (odds ratio 0.84; 95% confidence interval 0.43-1.63; p = 0.60). Ticagrelor was associated with a significantly higher risk of PLATO-defined major bleeding compared to clopidogrel (odds ratio 1.52; 95% confidence interval 1.04-2.23; p = 0.03).. Our meta-analysis demonstrated that ticagrelor was associated with a higher risk of major bleeding compared to clopidogrel in East Asian patients with ACS. Further studies evaluating the role of ticagrelor in management of ACS in East Asian patients are warranted.

Topics: Acute Coronary Syndrome; Aged; Asia, Eastern; Asian People; Blood Platelets; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Platelet Function Tests; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Ticagrelor; Treatment Outcome

Clopidogrel is the standard P2Y. A systematic electronic literature search was performed in MEDLINE, EMBASE, and the Cochrane Library for randomised controlled studies that examined the relative safety and efficacy of clopidogrel versus ticagrelor among patients requiring therapy with antiplatelet agents plus OAC.. Three randomised controlled trials were identified with a total of 5659 patients. The risk of clinically significant bleeding was significantly increased among patients on dual or triple antithrombotic therapy who received ticagrelor compared with patients on clopidogrel (OR 1.52, 95% CI 1.12 to 2.06, and OR 1.7, 95% CI 1.24 to 2.33, respectively). Among those on triple therapy, ticagrelor was associated with a significantly higher risk of major adverse cardiovascular events (MACE) compared to clopidogrel (OR 1.88, 95% CI 1.26 to 2.80). Patients who received dual therapy exhibited similar risk of MACE and stroke with ticagrelor versus clopidogrel (OR 1.14, 95% CI 0.83 to 1.56, and OR 0.42, 95% CI 0.10 to 1.74, respectively).. The use of ticagrelor as part of dual or triple antithrombotic therapy is associated with significantly higher rates of clinically relevant haemorrhagic complications compared with clopidogrel. Among triple therapy-treated patients, the use of ticagrelor might increase thromboembolic and ischaemic cardiac events.

Topics: Administration, Oral; Anticoagulants; Clopidogrel; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk Assessment; Risk Factors; Ticagrelor; Treatment Outcome

Cardiovascular disease (CVD) is the main cause of death in the world. Coronary artery disease (CAD) is the most common form of CVD presentation, but the prevalence of peripheral artery disease (PAD) is increasing. Patients with polyvascular disease comprise a very high-risk population that has been infrequently studied. Areas covered: The authors review the current evidence of the efficacy and safety of ticagrelor in the setting of acute coronary syndrome and stable patients post-MI with and without PAD and summarize its pharmacokinetics, pharmacodynamics, and regulatory issues. Expert opinion: Randomized studies showed that ticagrelor is superior to clopidogrel in patients with acute coronary syndromes, and is superior to placebo in the chronic phase (>1 year) post-myocardial infarction. Sub-analyses of these studies suggest that patients with myocardial infarction and PAD, compared to patients without these characteristics, may have greater benefit with ticagrelor. Nonetheless, the global evidence about the role of ticagrelor in patients with myocardial infarction and PAD remains relatively sparse, and a prospective randomized trial testing this hypothesis would be necessary to provide more definite data regarding the efficacy and safety of ticagrelor in this very high-risk population.

Topics: Acute Coronary Syndrome; Adenosine; Government Regulation; Half-Life; Hemorrhage; Humans; Myocardial Infarction; Peripheral Arterial Disease; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

Dual antiplatelet therapy with aspirin and clopidogrel are recommended as adjuncts to fibrinolytic-treated patients with ST-elevation myocardial infarction (STEMI). However, the role of switching to ticagrelor within 24 h of fibrinolytics compared with clopidogrel continuation in this setting is uncertain. Hence, we conducted a comprehensive search of electronic databases for all randomized clinical trials (RCTs) that evaluated the safety and efficacy of ticagrelor versus clopidogrel after fibrinolytic therapy in patients with STEMI. A random-effects model was used to calculate the risk ratios (RRs) and 95% confidence intervals (CIs). A total of 5 RCTs that evaluated the efficacy of ticagrelor post-fibrinolysis were identified. We included 3 RCTs with 3999 total patients for our meta-analysis. The results showed similar short-term clinical outcomes between ticagrelor and clopidogrel with regard to rates of Bleeding Academic Research Consortium (BARC) type ≥ 2 bleeding (RR 0.94; 95% CI 0.56-1.60; P = 0.83), major adverse cardiovascular events (RR 0.87; 95% CI 0.49-1.52; P = 0.62), mortality (RR 0.92; 95% CI 0.53-1.59; P = 0.77), myocardial infarction (RR 0.76; 95% CI 0.43-1.36; P = 0.36), and stroke (RR 0.93; 95% CI 0.50-1.73; P = 0.82). Our results demonstrate that in STEMI patients treated with fibrinolytic therapy, switching to ticagrelor was associated with similar bleeding and ischemic outcomes compared with clopidogrel continuation.

Topics: Cardiovascular Diseases; Clopidogrel; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; ST Elevation Myocardial Infarction; Stroke; Survival Analysis; Thrombolytic Therapy; Ticagrelor

 The clinical benefit of anti-platelet agents in patients with chronic kidney disease (CKD) is uncertain. In addition, the risk-benefit ratio of potent oral P2Y12-adenosine diphosphate (ADP) receptor antagonists (PPAs), namely, prasugrel and ticagrelor, compared with clopidogrel in CKD patients suffering from acute coronary syndrome (ACS) remains unknown..  We performed a meta-analysis of all studies comparing the clinical outcomes of PPA and clopidogrel therapy in CKD patients suffering from ACS..  We searched PubMed, the Cochrane library, Google Scholar, Clinical trial.org and the abstracts of international cardiology congresses from April 2000 to October 2017. Clinical studies comparing PPA with clopidogrel in ACS patients with CKD were selected. Our literature research identified five studies which were included in the meta-analysis. The primary endpoint was a composite of major adverse cardiovascular events (MACEs) at the latest follow-up available. Secondary endpoint included bleedings..  Compared with clopidogrel, PPAs were associated with a reduced rate of MACE without increased bleedings in CKD patients with ACS. Among invasively managed patients, this benefit from PPA included a reduction in mortality.

Topics: Acute Coronary Syndrome; Administration, Oral; Clopidogrel; Drug-Related Side Effects and Adverse Reactions; France; Hemorrhage; Humans; Odds Ratio; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Survival Analysis; Ticagrelor; Treatment Outcome

Ticagrelor has been acknowledged as a new oral antagonist of P2Y12-adenosine diphosphate receptor, as a strategy with more rapid onset as well as more significant platelet inhibition function in acute coronary syndrome (ACS) patients. The clinical benefit of ticagrelor compared with clopidogrel remains controversial. The current meta-analysis was conducted to better evaluate the role of ticagrelor in comparison of clopidogrel in treating ACS patients.. The publications involving the safety as well as the efficacy of clopidogrel versus ticagrelor were screened and identified updated to June 2018. After rigorous review, eligible randomized controlled trials (RCTs) were extracted and propensity score matching (PSM) analysis was conducted. To analyze the summary odds ratios (ORs) of the endpoints of interest, we applied Meta-analysis Revman 5.3 software.. There were a total of 10 studies that met our inclusion criteria, of which the risk of bleeding rate (P = 0.43), MI (P = 0.14), and stroke (P = 0.70) had no association with significant differences between patients receiving ticagrelor or clopidogrel. Nonetheless, higher rate of dyspnea was observed in ticagrelor group (OR = 1.87, 95% CI: 1.70-2.05, P<0.00001 = .. Our present findings suggest similar efficacy and safety profiles for clopidogrel and ticagrelor Ticagrelor should be considered as a valuable option to reduce the risk of bleeding, MI and stroke, whereas potentially increases the incidence of dyspnea. Given the metabolic process, ticagrelor may be a valid and even more potent antiplatelet drug than clopidogrel, as an alternative strategy in treating patients with clopidogrel intolerance or resistance.

Topics: Acute Coronary Syndrome; Clopidogrel; Dyspnea; Hemorrhage; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Factors; Ticagrelor; Treatment Outcome

Like all antithrombotic drugs, antiplatelet agents expose to a risk of bleeding complications. Clinical research has extensively focused on the efficacy of these drugs to reduce ischemic events. The bleeding risk associated with them was solely considered as an inevitable and acceptable complication. When two new potent P2Y12-receptor inhibitors, prasugrel and ticagrelor, were marketed, the risk of major bleeding increased. These new agents have modified the balance between the absolute risk reduction in ischemic events and the absolute risk increase in bleeding events. This paper is an update on the bleeding risk assessment associated with antiplatelet agents. It discusses the place of platelet function monitoring, and the optimal management of bleeding complications. It addresses the challenging issue of reversal of antiplatelet therapy, focusing especially on ticagrelor, which pharmacodynamics complicate bleeding management.

Topics: Adenosine; Aspirin; Clopidogrel; Drug-Related Side Effects and Adverse Reactions; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor; Ticlopidine

Antiplatelet agents are at risk for bleeding complications, the management of which differs depending on the clinical situation and on the antiplatelet agent itself. Neutralization of antiplatelets is sometimes necessary, most often leading to platelet transfusion, although the benefit of this strategy is poorly documented. In addition, if platelet transfusion corrects the platelet inhibition induced by aspirin and probably by clopidogrel and prasugrel, it does not neutralize ticagrelor, as a consequence of its pharmacological properties. The clinical benefit of platelet transfusion is limited, and the most recent studies are challenging it. However, it is indicated on a perioperative basis for surgeries with high hemorrhagic risk and is discussed in severe hemorrhages. The neutralization of ticagrelor is a concern and the antidote currently under development may be a solution. In all cases, other therapeutic solutions may be considered, such as administration of desmopressin, tranexamic acid or activated factor VII.

Topics: Adenosine; Antidotes; Aspirin; Clopidogrel; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Platelet Transfusion; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Risk; Ticagrelor; Ticlopidine

Topics: Adenosine; Cardiovascular Diseases; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Hemorrhage; Humans; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Stroke; Ticagrelor

This review aims to summarize and discuss safety and effectiveness of the long-term use of ticagrelor in patients with coronary artery disease (CAD).. Ticagrelor is an orally administered, direct, and reversible inhibitor of the P2Y

Topics: Adenosine; Blood Platelets; Coronary Artery Disease; Hemorrhage; Humans; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Thrombosis; Ticagrelor; Treatment Outcome

High on-clopidogrel platelet reactivity (HcPR) during dual-antiplatelet therapy is a marker of vascular risk, in particular stent thrombosis, in patients with acute coronary syndromes (ACS). Genetic determinants (CYP2C19*2 polymorphism), advanced age, female gender, diabetes and reduced ventricular function are related to a higher risk to develop HcPR. In addition, inflammation and increased platelet turnover, as revealed by the elevated percentage of reticulated platelets in patients' blood, that characterize the acute phase of acute coronary syndromes, are associated with HcPR. To overcome the limitation of clopidogrel, new antiplatelet agents (prasugrel and ticagrelor) were developed and the demonstration of their superiority over clopidogrel was obtained in the two randomized trials, TRITON TIMI 38 and PLATO. Emerging evidence is accumulating on the role of high-on aspirin platelet reactivity (HaPR), especially in the clinical context of diabetes. Finally, the presence of new, potent antiplatelet drugs has shifted the focus from thrombotic to bleeding risk. Recent data document that low on-treatment platelet reactivity (LPR) is associated with a significantly higher bleeding risk. Due to the current possibility to choose between multiple antiplatelet strategies, the future perspective is to include in the management of ACS, in addition to clinical data and classical risk factors, the definition of platelet function during treatment in order to set a tailored therapy.

Topics: Acute Coronary Syndrome; Adenosine; Age Factors; Blood Platelets; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Interactions; Hemorrhage; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Prasugrel Hydrochloride; Sex Factors; Stents; Thrombosis; Ticagrelor; Ticlopidine

Dual antiplatelet therapy (DAPT) is standard treatment for patients with acute coronary syndromes (ACS), typically comprising the use of aspirin with either an irreversible thienopyridine P2Y12 inhibitor, clopidogrel or prasugrel, or reversibly binding ticagrelor. Pivotal studies led to guidelines recommending DAPT for up to 12 months post-ACS. Despite this, there remains a significant burden of coronary artery disease (CAD)-related events up to and after this period. Recent meta-analyses, including both patients with ACS and patients with stable CAD treated with DAPT following percutaneous coronary intervention, have suggested that long-term thienopyridine-based DAPT reduces the risks of myocardial infarction (MI) and stent thrombosis but may paradoxically increase all-cause mortality risk. The PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin - Thrombolysis in Myocardial Infarction 54) study examined the effects of long-term DAPT with aspirin and ticagrelor, compared with aspirin alone, on major adverse cardiovascular events (MACE) and complications, including bleeding in patients with prior history of MI. It showed that, over a 3-year period, ticagrelor reduced the risk of MACE but increased non-fatal bleeding risk. Overall, the PEGASUS-TIMI 54 results demonstrate that patients with a history of ACS deemed to be at high risk of further ischaemic events, particularly those in whom the risks of ischaemic events and cardiovascular death outweigh the risk of life-threatening bleeding, may benefit from prolonged ticagrelor-based DAPT. Guidelines are emerging which reflect this. The relationship between aspirin and ticagrelor, particularly with regard to aspirin dosing, remains to be fully elucidated and attention has recently been turned to the option of ticagrelor monotherapy. Future studies will explore optimal individualised strategies for long-term antiplatelet therapy.

Topics: Adenosine; Aspirin; Clopidogrel; Drug Administration Schedule; Drug Therapy, Combination; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Recurrence; Risk Assessment; Risk Factors; Secondary Prevention; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

It is estimated that in the United States, each year, approximately 620,000 persons will experience an acute coronary syndrome and approximately 70% of these will have non-ST-elevation acute coronary syndrome. Cardiovascular disease still accounts for 1 of every 3 deaths in the United States, and there is an urgent need to improve the prognosis of patients presenting with acute coronary syndrome. Cardiovascular mortality and ischemic complications are common after acute coronary syndrome, and the advent of newer antithrombotic therapies has reduced ischemic complications, but at the expense of greater bleeding. The new antithrombotic agents also raise the challenge of choosing between multiple potential therapeutic combinations to minimize recurrent ischemia without a concomitant increase in bleeding, a decision that often varies according to an individual patient's relative propensity for ischemia versus hemorrhage. In this review, we will synthesize the available information to arm health care providers with the contemporary knowledge on antithrombotic therapy and individualize treatment decisions.

Topics: Acute Coronary Syndrome; Adenosine; Adenosine Monophosphate; Anticoagulants; Antithrombins; Clinical Trials as Topic; Cytochrome P-450 CYP2C19; Drug Therapy, Combination; Factor Xa Inhibitors; Fibrinolytic Agents; Genotype; Hemorrhage; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polymorphism, Genetic; Practice Guidelines as Topic; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor

Aspirin was established more than a quarter century ago as an evidence-based therapy to reduce recurrent cardiovascular events in patients with coronary artery disease based on limited data by contemporary standards. Indeed it is unclear how regulatory agencies would define the optimal dose or duration of aspirin therapy if assessed in the current era. Subsequent clinical investigation has focused on the addition of antithrombotic agents on top of baseline aspirin therapy in the acute and chronic setting to reduce patient's risk of further ischemic events, at the cost of increased bleeding complications. The current armamentarium of potent and predictable antiplatelet and antithrombotic agents has ushered in a new era where clinicians and scientists are contemplating withdrawal of previously established agents to minimize bleeding risk while sustaining efficacy; indeed, subtraction may lead to the next advance in the treatment of acute and chronic ischemic vascular disease.

Topics: Adenosine; Antithrombins; Aspirin; Clopidogrel; Drug Therapy, Combination; Evidence-Based Medicine; Factor Xa Inhibitors; Hemorrhage; History, 20th Century; History, 21st Century; History, Ancient; Humans; Myocardial Ischemia; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Ticagrelor; Ticlopidine

Ticagrelor (Brilique™, Brilinta®), a cyclopentyl-triazolopyrimidine, is an orally active, reversible, and selective adenosine diphosphate (ADP) receptor antagonist indicated for use in patients with acute coronary syndromes (ACS). Ticagrelor has a faster onset of action and provides greater inhibition of platelet aggregation than clopidogrel. In the large well-designed, PLATO study in adult patients with ACS, 12 months' treatment with ticagrelor was more effective than clopidogrel in reducing the incidence of the primary composite endpoint of myocardial infarction, stroke, or cardiovascular (CV) death. Ticagrelor also reduced all-cause mortality relative to clopidogrel, although statistical significance of this was not confirmed in hierarchical testing. Benefit with ticagrelor was seen both in invasively and noninvasively managed patients. Ticagrelor was generally well tolerated and was not associated with an increased risk of major bleeding relative to clopidogrel. However, the incidences of non-coronary artery bypass grafting (CABG)-related bleeding, and major or minor bleeding, as well as some non-hemorrhagic adverse events, including dyspnea (usually of mild or moderate severity) and ventricular pauses (largely asymptomatic) were higher with ticagrelor. In addition, the ATLANTIC study showed that although pre-hospital administration of ticagrelor did not improve pre-percutaneous coronary intervention (PCI) coronary reperfusion in ACS patients relative to in-hospital administration, ticagrelor was safe in both instances, with no significant between-group differences in non-CABG-related major and minor bleeding events. Although further comparative studies with other antiplatelet agents, including prasugrel, are required to position it more definitively, current evidence indicates that ticagrelor is a useful option for the prevention of thrombotic CV events in ACS patients managed invasively or noninvasively.

Topics: Acute Coronary Syndrome; Adenosine; Administration, Oral; Aging; Combined Modality Therapy; Coronary Artery Bypass; Evidence-Based Medicine; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk; Thrombosis; Ticagrelor

Ticagrelor is recommended in local and international guidelines as first-line therapy in combination with aspirin in patients presenting with acute coronary syndromes (ACS). The purpose of this article is to provide practical guidance regarding the use of ticagrelor in this setting.. Ticagrelor, a direct-acting, reversible P2Y12 receptor antagonist, has a faster onset, and a more potent and predictable antiplatelet effect compared with clopidogrel. The authors recommend considering the use of ticagrelor in moderate-to-high risk ACS patients treated with an invasive approach and those managed non-invasively who have elevated troponin levels. Consistent with outcomes observed in the PLATO trial overall, ticagrelor was superior to clopidogrel treatment in patients with chronic kidney disease, a history of stroke or transient ischemic attack, the elderly, and patients requiring surgical revascularization.. When switching from clopidogrel to ticagrelor, patients established on clopidogrel therapy can be switched directly without loading; patients not loaded with clopidogrel and not taking maintenance dose clopidogrel for at least 5 days should first be loaded with ticagrelor. Guidelines recommend discontinuing ticagrelor 5 days before surgery if antiplatelet effects are not desired and recommencing therapy as soon as safe following surgery. Ticagrelor should be avoided in individuals with a history of intracranial hemorrhage, moderate-to-severe hepatic impairment, high bleeding risk, within 24 hours of thrombolytic therapy, and in those treated with oral anticoagulants. Local, real-world experience suggests low bleeding rates with ticagrelor therapy. Dyspnoea is a common symptom in patients with ACS and is also a side-effect of ticagrelor therapy. Discontinuation of ticagrelor due to dyspnoea has been uncommon in clinical trials. However, local registry data suggest higher discontinuation rates (2-9%) related to dyspnoea in the real-world setting, indicating that clinicians may need to consider other potential causes of dyspnoea before discontinuing ticagrelor.

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine

Clopidogrel, prasugrel, and ticagrelor are the currently available oral P2Y12 inhibitors for the treatment of ST-segment elevation myocardial infarction (STEMI), in association with aspirin. These agents bind the P2Y12 platelet receptor and thus inhibit platelet aggregation. Large randomized clinical trials have provided efficacy and safety data on P2Y12 inhibitors in STEMI patients.. This review focuses on key pharmacologic and clinical aspects of clopidogrel, prasugrel, and ticagrelor, highlighting their differences. Results from the main clinical trials are discussed, as well as the current STEMI guideline recommendations, to help inform agent selection for patients presenting with STEMI.. Clinical trials studying newer P2Y12 inhibitors with increased potency have shown further reduction of cardiovascular events compared with clopidogrel, therefore suggesting the use of ticagrelor or prasugrel as a first-line agent for STEMI treatment. There are still clinical situations - such as fibrinolysis, high risk of bleeding, use of oral anticoagulant, and financial hurdles - in which clopidogrel maintains a role in the treatment of STEMI.

Topics: Adenosine; Aspirin; Clopidogrel; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Ticagrelor; Ticlopidine; Treatment Outcome

Coronary thrombosis is a frequent cause of death and myocardial infarction most often explained by superimposition of a platelet-rich thrombus on existing coronary artery disease. Therefore, antiplatelet drugs are essential in the treatment and secondary prevention of acute coronary syndromes (ACS) and during percutaneous coronary intervention. Several novel antiplatelet drugs are now available.. For several years, aspirin and clopidogrel remained the cornerstone of treatment for ACS. However, prasugrel and ticagrelor have a more consistent, faster-acting and more potent antiplatelet effect than clopidogrel, which translates into improved clinical outcomes, although at the expense of an increased bleeding risk. Importantly, some patients experience cardiovascular events despite current antiplatelet treatment, because platelet activation may occur via pathways not inhibited by these agents. Therefore, improved antiplatelet strategies are warranted.. Despite undisputable benefits of current antiplatelet strategies, a considerable number of patients continue to experience adverse thrombotic events, although clinical outcomes have been improved with new oral P2Y₁₂ antagonists. New drugs have been developed, including intravenous P2Y₁₂ antagonists and oral antagonist targeting the protease-activated receptor-1 platelet activation pathway stimulated by thrombin. This review provides an overview of current and novel antiplatelet strategies and also discusses unmet needs related to antiplatelet therapy for ACS.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Clopidogrel; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptor, PAR-1; Receptors, Purinergic P2Y12; Ticagrelor; Ticlopidine

The optimal utilization of antiplatelet therapy in patients with renal impairment (RI) following acute coronary syndromes (ACS) represents an urgent, unmet and yet unsolved need with regards to the choice of agents, duration of treatment and potential dose/regimen adjustment. The lack of any large randomized trials designed and powered specifically in such high-risk patients, absence of the uniformed efficacy and safety data reporting policy to the FDA and endless overoptimistic publications based on post hoc analyses of primary trials sometimes exaggerating benefits and hiding risks, clouds reality. In addition, triaging RI patients is problematic due to ongoing kidney deterioration and the fact that such patients are prone to both vascular occlusions and bleeding. The authors summarize available FDA-confirmed evidence from the latest trials with approved antiplatelet agents, namely clopidogrel (CAPRIE, CURE, CREDO, CLARITY, CHARISMA); prasugrel (TRITON, TRILOGY); ticagrelor (PLATO, and PEGASUS); and vorapaxar (TRACER and TRA2P) in RI patient cohorts on top of aspirin as part of dual antiplatelet therapy (DAPT). We deliberately avoided any results unless they were verified by the FDA, with the exception of the recent PEGASUS, since Agency reviews are not yet available. Despite differences among the trials and DAPT choices, RI patients universally experience much higher (HR = 1.3-3.1) rates of primary endpoint events, and bleeding risks (HR = 1.7-3.6). However, only ticagrelor increases creatinine and uric acid levels above that of clopidogrel; has the worst incidence of serious adverse events, more adverse events, and inferior outcomes in patients with severe (eGFR <30 ml/min), especially in the lowest (eGFR <15 ml/min) RI subsets. Clopidogrel, prasugrel and vorapaxar appear safer. Moreover, less aggressive half dose (5 mg/daily) prasugrel and strict DAPT, are well justified in RI, but not predominantly triple strategies with vorapaxar as tested in TRA2P and especially in TRACER. In conclusion, data from clinical trials, their sub-studies and affiliated FDA reviews indicate that RI cause more vascular occlusions and bleeding in ACS patients treated with DAPT. Among the novel antiplatelet agents, prasugrel and vorapaxar, but probably not ticagrelor, offer advantage in RI patients.

Topics: Acute Coronary Syndrome; Adenosine; Clinical Trials as Topic; Clopidogrel; Comparative Effectiveness Research; Glomerular Filtration Rate; Hemorrhage; Humans; Lactones; Patient Selection; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyridines; Renal Insufficiency; Ticagrelor; Ticlopidine

P2Y12 receptor antagonists have become cornerstone pharmacological agents in antiplatelet therapy for patients with acute coronary syndrome or undergoing percutaneous coronary intervention. While clopidogrel remains in extensive use in clinical practice, it cannot meet the needs in many clinical conditions because of its pharmacological limitations. In recent years, newly developed P2Y12 antagonists, such as prasugrel and ticagrelor, have proven to be of higher efficacy and less resistance. With the introduction of these new medicines, the current antiplatelet strategy is undergoing a transitional period. Insufficient platelet inhibition (high platelet reactivity) leads to an increased risk of ischemic events whereas exceeding platelet inhibition can lead to an increased risk of bleeding. This review discusses the pharmacological features, benefits, risks and cost-effectiveness of different P2Y12 antagonists in various clinical settings. A balance between these factors will determine the choice of P2Y12 antagonists for personalized antiplatelet therapy. We conclude that it is a promising option to apply the new drugs, due to their superior therapeutic performance versus that of clopidogrel in the long run.

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Hemorrhage; Humans; Piperazines; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Risk Factors; Thiophenes; Ticagrelor; Ticlopidine

Dual antiplatelet therapy is the cornerstone of maintenance medication following invasive treatment of patients with acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction, unstable angina). Over the last decade, P2Y12 inhibition in addition to low-dose acetylsalicylic acid has been intensively debated. The debate was enriched by the results of the large phase III clinical trials for prasugrel (TRITON) and ticagrelor (PLATO) compared to clopidogrel in patients with acute coronary syndromes. This article summarizes the critical details und subanalyses of both study programmes and highlights on clinical decision making when using the three P2Y12 blockers in acute coronary syndromes. A special focus is on higher risk patients such as those with ST elevation myocardial infarction and those with coexisting diabetes, but also on minimizing relevant bleedings, which are common during more intense platelet inhibition.

Topics: Acute Coronary Syndrome; Adenosine; Angina, Unstable; Aspirin; Blood Platelets; Clopidogrel; Hemorrhage; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Platelet Transfusion; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Ticlopidine

The dual antiplatelet therapy with acetylsalicylic acid and clopidogrel has been the mainstay of both acute and chronic phase coronary artery disease, reducing importantly the risk of adverse events. Despite a correct compliance, a non-negligible rate of adverse events still happens. New compounds, with improved properties, are now clinically available (such as prasugrel or ticagrelor) or under advanced development. The aim of the present review is the description of these new compounds, particularly prasugrel and ticagrelor.

Topics: Adenosine; Adenosine Monophosphate; Clinical Trials, Phase III as Topic; Coronary Artery Disease; Double-Blind Method; Dyspnea; Hemorrhage; Humans; Multicenter Studies as Topic; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Receptors, Proteinase-Activated; Thiophenes; Ticagrelor; Treatment Outcome

Clopidogrel is a prodrug that undergoes extensive enteric clearance and requires two-stage hepatic activation by cytochrome P450 (CYP) enzymes. This metabolic pathway is susceptible to genetic polymorphisms, resulting in a variable platelet inhibitory effect. A growing number of studies have linked poor antiplatelet response to clopidogrel to adverse clinical outcomes, particularly coronary ischemic events and stent thrombosis. This has prompted the development of new ADP receptor antagonists that inhibit platelets more effectively. Two of these agents, prasugrel and ticagrelor, have been investigated in two large randomized clinical trials, and both have shown superiority versus clopidogrel in reducing ischemic endpoints, with an increase in bleeding events, but a favorable final net clinical outcome. Since the publication of the main articles, several sub-analyses have been performed on the same data, and Guideline recommendations have largely endorsed these subgroup findings. Most clinicians have accepted the concept that we might consider approaching the patient differently, deserving a specific agent for each different settings. However, subgroup analyses of randomized trials are often post hoc, underpowered and prone to bias. Weighing efficacy and safety of the most commonly used antiplatelet agents will represent a clinical challenge over the next few years. Furthermore, individuals and organizations involved in formulary decisions will have to face economic constraints, also taking into account the availability of low-cost generic clopidogrel. In the following review, we have performed a critical appraisal of the current literature in order to outline lights and shadows on the most relevant clinical scenarios.

Topics: Adenosine; Hemorrhage; Humans; Patient Selection; Piperazines; Platelet Activation; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Risk Assessment; Risk Factors; Thiophenes; Ticagrelor; Treatment Outcome

New P2Y12 inhibitors can be classified as oral (prasugrel and ticagrelor) and intravenous drugs (cangrelor and elinogrel). These P2Y12 inhibitors might be superior to clopidogrel for reducing ischemic events in patients with coronary artery disease (CAD). We performed a meta-analysis of randomized trials that compared new oral or intravenous P2Y12 inhibitors with clopidogrel to determine their efficacy and safety in patients.. Twelve randomized, placebo-controlled studies and two subgroup analyses of included studies on ST-segment elevation myocardial infarction (STEMI) were included. The database consisted of 82,784 patients, with 43,875 (53%) on new oral P2Y12 inhibitors and 38909 (47%) on intravenous P2Y12 inhibitors compared with clopidogrel. The primary efficacy endpoint was major adverse cardiac events (MACEs). The primary safety endpoint was thrombolysis in myocardial infarction (TIMI) major bleeding. New oral P2Y12 inhibitors significantly decreased MACEs (odds ratio: 0.85, p<0.0001 for the whole cohort; OR: 0.77, p=0.04 for STEMI) and all-cause death (OR: 0.88, p=0.04 for the whole cohort; OR: 0.77, p=0.01 for STEMI). Among new intravenous P2Y12 inhibitors, only cangrelor significantly decreased the risk of MACEs. An increase in TIMI major bleeding was observed only by prasugrel among the new P2Y12 inhibitors.. New oral P2Y12 inhibitors reduce ischemic events, but there is no obvious increase in major bleeding in patients with CAD, and the risk/benefit ratio is particularly favorable for STEMI patients. Moreover, only cangrelor is beneficial for ischemic events in patients on new intravenous P2Y12 inhibitors.

Topics: Acute Coronary Syndrome; Adenosine; Adenosine Monophosphate; Administration, Oral; Clopidogrel; Coronary Artery Disease; Coronary Restenosis; Fibrinolytic Agents; Hemorrhage; Humans; Injections, Intravenous; Multicenter Studies as Topic; Myocardial Infarction; Piperazines; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Quinazolinones; Randomized Controlled Trials as Topic; Stents; Stroke; Sulfonamides; Thiophenes; Thrombolytic Therapy; Ticagrelor; Ticlopidine

Topics: Acute Coronary Syndrome; Adenosine; Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Hemorrhage; Humans; Morpholines; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Postoperative Complications; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thrombosis; Ticagrelor

Effective antagonism of the P2Y12 platelet receptor is central to the treatment of acute coronary syndrome (ACS) patients, especially in the setting of percutaneous coronary intervention and stenting. According to consensus guidelines, early revascularization and intensive antiplatelet therapy are key to reducing the complications that arise from myocardial ischaemia and the recurrence of cardiovascular events. Until recently, clopidogrel was the key P2Y12 antagonist advocated, but due to several limitations as an antiplatelet agent, newer drugs with more predictable, rapid and potent effects have been developed. Prasugrel and ticagrelor are now the recommended first-line agents in patients presenting with non-ST-segment elevation ACS and ST-segment elevation ACS, due to large-scale randomized trials that demonstrated net clinical benefit of these agents over clopidogrel, as stated in the European guidelines. Although no study has directly compared the two agents, analysis of the data to date suggests that certain patient types, such as diabetics, those with ST-segment elevation myocardial infarction or renal failure and the elderly may have a better outcome with one agent over the other. Further studies are needed to confirm these differences and answer pending questions regarding the use of these drugs to optimize efficacy while minimizing adverse events, such as bleeding. The aim of this review is to provide an overview of the current P2Y12 receptor antagonists in the treatment of ACS, with a focus on issues of appropriate agent selection, timing of treatment, bleeding risk and the future role of personalized treatment using platelet function and genetic testing.

Topics: Acute Coronary Syndrome; Adenosine; Adenosine Monophosphate; Clinical Trials as Topic; Clopidogrel; Combined Modality Therapy; Coronary Artery Bypass; Coronary Thrombosis; Diabetes Complications; Hemorrhage; Humans; Multicenter Studies as Topic; Piperazines; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Precision Medicine; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Receptors, Purinergic P2Y12; Renal Insufficiency; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

Numerous clinical trials testing the efficacy of aspirin for the secondary prevention of cardiovascular disease have been published. We reviewed the literature pertaining to aspirin dose in acute coronary syndrome patients. Clinical trials assessing the comparative efficacy of different doses of aspirin are scarce. This complex antiplatelet therapy landscape makes it difficult to identify the best aspirin dose for optimizing efficacy and minimizing risk of adverse events, while complying with the various guidelines and recommendations. Despite this fact, current evidence suggests that aspirin doses of 75-100 mg/day may offer the optimal benefit:risk ratio in acute coronary syndrome patients.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Dose-Response Relationship, Drug; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Thiophenes; Ticagrelor

The introduction of clopidogrel was a milestone in the development of modern antiplatelet therapy. However, the shortcomings in the pharmacokinetics of clopidogrel have led to the development of alternative substances.. The two new drugs prasugrel and ticagrelor were included in the current guidelines for the treatment of patients with acute coronary syndrome. These potent platelet inhibitors, however, are associated with an increased rate of bleeding events, which is of particular importance in critically ill patients. However, the new platelet inhibitors are less effective in patients with cardiogenic shock or patients treated with therapeutic hypothermia.. Recent studies underscore the assessment of the net clinical benefit in patient management. Since there is only a thin line between efficacy and safety in critically ill patients, future studies for risk stratification of antiplatelet therapy in terms of personalized medicine are mandatory.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Germany; Guideline Adherence; Hemorrhage; Humans; Hypothermia, Induced; Intensive Care Units; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Precision Medicine; Risk Assessment; Shock, Cardiogenic; Survival Rate; Ticagrelor; Ticlopidine; Treatment Outcome

Topics: Acute Coronary Syndrome; Adenosine; Hemorrhage; Humans; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

Topics: Adenosine; Cardiac Surgical Procedures; Clopidogrel; Hemorrhage; Humans; Perioperative Care; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2; Receptors, Purinergic P2Y12; Surgical Procedures, Operative; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

The initial 2010 Canadian Cardiovascular Society (CCS) Guidelines for the Use of Antiplatelet Therapy in the Outpatient Setting were published in May 2011. As part of a planned re-evaluation within 2 years, we conducted an extensive literature search encompassing all topics included in the 2010 CCS Guidelines, and concluded that there were sufficient new data to merit revisiting the guidance on antiplatelet therapy for secondary prevention in the first year after acute coronary syndrome (ACS), percutaneous coronary intervention, or coronary artery bypass grafting, and the interaction between clopidogrel and proton pump inhibitors. In addition, new clinical trials information about the efficacy and safety of combining novel oral anticoagulants with antiplatelet therapy in ACS justified the addition of a new section of recommendations to the Guidelines. In this focused update, we provide recommendations for the use of clopidogrel, ticagrelor, and prasugrel in non-ST elevation ACS, avoidance of prasugrel in patients with previous stroke/transient ischemic attack, higher doses of clopidogrel (j) /day) for the first 6 days after ACS, and the preferential use of prasugrel or ticagrelor after percutaneous coronary intervention in ACS. For non-ACS stented patients, we recommend acetylsalicylic acid/clopidogrel for 1 year, with at least 1 month of therapy for bare-metal stent patients and 3 months for drug-eluting stent patients unable to tolerate year-long double therapy. We also consider therapy for patients with a history of stent thrombosis, the indications for longer-term treatment, discontinuation timing preoperatively, indications for changing agents, the management of antiplatelet therapy before and after bypass surgery, and use/selection of proton pump inhibitors along with antiplatelet agents.

Topics: Acute Coronary Syndrome; Adenosine; Anticoagulants; Aspirin; Clinical Trials as Topic; Clopidogrel; Contraindications; Coronary Artery Bypass; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proton Pump Inhibitors; Secondary Prevention; Stents; Stroke; Thiophenes; Thrombosis; Ticagrelor; Ticlopidine

The most common risks related to platelet inhibitor therapy are bleeding, drug-drug interactions and therapeutic failure. The new substances prasugrel and ticagrelor are more potent platelet inhibitiors than clopidogrel. This reduces the incidence of ischemic events, but also potentially increases the bleeding risk. Clopidogrel therapy has up to 20% non-response rates, which can partially be explained by genetic polymorphisms and drug-drug interactions. Currently no evidence exists that ticagrelor or prasugrel efficacy is affected by genetic polymorphisms. The therapy in patients at risk still has to be carefully adapted to minimize adverse events. Patients older than 75 years and/or weighing less than 60 kg should receive a reduced dose of prasugrel. The combination of ticagrelor with strong cytochrome-P450-3A4 inhibitors is contraindicated.. Blutungsereignisse, Arzneimittelwechselwirkungen und Therapieversagen sind relevante Risiken einer Therapie mit Plättchenaggregationshemmern. Die neuen Substanzen Prasugrel und Ticagrelor sind stärker wirksam als Clopidogrel und senken ischämische Ereignisse bei Patienten mit akutem Koronarsyndrom effizienter. Sie erhöhen allerdings potenziell auch die Blutungsraten. Eine Therapie mit Clopidogrel birgt das Risiko einer Therapieresistenz bei bis zu 20% der Patienten, die u. a. auf genetischen Polymorphismen und Arzneimittelinteraktionen beruht. Für Prasugrel und Ticagrelor bestehen keine Hinweise, dass genetische Polymorphismen die Wirksamkeit beeinflussen. In Risikosituationen muss die Therapie jedoch sorgfältig angepasst werden, um unerwünschte Wirkungen zu minimieren: So wird bei Patienten >75 Jahre und/oder einem Körpergewicht <60 kg aufgrund des erhöhten Blutungsrisikos eine Prasugrel-Dosisreduktion empfohlen. Ticagrelor ist in Kombination mit starken Cytochrom-P450–3A4-Hemmern kontraindiziert.. Les événements hémorragiques, les interactions médicamenteuses et l'échec de thérapie constituent les risques majeurs des traitements à base d'antiagrégants plaquettaires. Les substances nouvelles, prasugrel et ticagrelor, présentent un effet anitagrégant plus important et diminuent les épisodes ischémiques d'une manière plus efficacement que le clopidogrel. Cependent la possibilité existe d'une augmentation d'épisodes de saignement. Le risque de résistance à la thérapie atteint jusqu'à 20% pour les patients traités à base de clopidogrel, entre autre en raison de polymorphismes génétiques. Il n'existe pas d'evidence pour un mécanisme pareil pour le prasugrel et le ticagrelor. Dans certaines situations de risque par contre, une adaption du dosage est conseillée pour minimiser les effets secondaires négatifs: Chez les patients de plus de 75 ans, et/ou d'un poids corporel de moins de 60 kg, une réduction du dosage de prasugrel est conseillée en raison d'un risque élevé d'hémorragie. Il est contrindiqué d'utiliser ticagrelor en combinaison avec des inhibiteurs puissants du cytochrome-P450–3A4.

Topics: Adenosine; Angioplasty, Balloon, Coronary; Aspirin; Clopidogrel; Coronary Disease; Drug Interactions; Drug Resistance; Drug Therapy, Combination; Hemorrhage; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Risk Factors; Stents; Thiophenes; Ticagrelor; Ticlopidine

The two newer antiplatelet drugs, prasugrel and ticagrelor have both been incorporated in various national guidelines and are both under consideration for approval or have already been approved by various drug regulatory authorities. Mortality benefits with clopidogrel were comparable to newer anti-platelets, and prasugrel had great anti-ischemic potency than ticagrelor. We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials' databases for randomized controlled trials conducted between 1990 and 2012 that assessed clinical outcomes with prasugrel or ticagrelor. The comparator was standard dosage of clopidogrel. Outcomes assessed were the risk of all causes mortality, TIMI non-CABG major bleeding, and a composite of stent thrombosis, recurrent ischemia and serious recurrent ischemia in the intervention groups versus the comparator groups. Event rates were compared using a forest plot of relative risk using a random effects model (Mantel-Haenszel); and Odd's ratio was calculated in the absence of significant heterogeneity. Prasugrel was indirectly compared with ticagrelor using network meta-analysis. Four studies (total N = 34,126) met the inclusion/exclusion criteria. Both drugs had improved mortality and greater risk of bleeding compared to clopidogrel; but outcomes were comparable for both (p = NS). However a composite of recurrent ischemic events, including rates of stent thrombosis (p = 0.045) was reduced to a modest degree with prasugrel compared with ticagrelor. This systematic review suggests greater clinical efficacy of both prasugrel and ticagrelor compared with clopidogrel and an indirect comparison indicates prasugrel may be more effective than ticagrelor for preventing stent thrombosis and recurrent ischemic events.

Topics: Adenosine; Clopidogrel; Hemorrhage; Humans; Ischemia; Piperazines; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; PubMed; Randomized Controlled Trials as Topic; Stents; Thiophenes; Thrombosis; Ticagrelor; Ticlopidine

Despite revascularisation, outcomes among patients presenting with ST-elevation myocardial infarction (STEMI) remain suboptimal.. This review compares clopidogrel, ticagrelor and prasugrel as antiplatelet strategies with a particular focus on STEMI. Medline and Google Scholar were searched for relevant terms and citations from these articles were also assessed.. While clopidogrel represented an important therapeutic advance, variations in platelet response and a relatively slow onset of action compromise outcomes in some patients. Ticagrelor and prasugrel are more effective than clopidogrel, although essentially only one large study supports each drug. Nevertheless, a detailed examination of the evidence reveals several issues that may influence the decision to prescribe ticagrelor instead of prasugrel and vice versa. Arguably, prasugrel could be the preferred strategy in STEMI, reflecting the drugs' efficacy in clopidogrel-naïve patients, the most common group in clinical practice. Conversely, ticagrelor may be a better option than clopidogrel in clopidogrel-pretreated patients showing a mortality benefit irrespective of clopidogrel pre-treatment. The clinical benefits offered by prasugrel and ticagrelor need to be offset against the increased cost and we suggest an algorithm for using these new compounds in the primary percutaneous coronary intervention (PCI) setting. The risk of bleeding associated with prasugrel is similar to that of clopidogrel and ticagrelor following exclusion of at-risk patients. Nevertheless, prasugrel may be especially appropriate for STEMI patients undergoing PCI who are considered to be at high risk of ischaemia. Conversely, ticagrelor's short half-life, while potentially a limitation during maintenance therapy, may reduce bleeding risk if the patient undergoes CABG during the same hospital admission, although confirmatory studies are needed.. Future studies also need to address several other outstanding issues, such as the subsequent approach if patients do not undergo PCI, and to overcome limitations in and differences between the primary studies. In particular, head-to-head comparisons need to compare directly the risks and benefits of ticagrelor and prasugrel in STEMI patients. These caveats notwithstanding, ticagrelor and prasugrel markedly improve the prognosis for patients with STEMI.

Topics: Adenosine; Clopidogrel; Hemorrhage; Humans; Myocardial Infarction; Myocardial Revascularization; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Thiophenes; Ticagrelor; Ticlopidine

The convention of loading with clopidogrel 300 mg before coronary intervention may be due for change, but to what? Newer antiplatelet agents may offer better outcomes, at some financial cost. Disappointingly for decision-making clinicians, head-to-head comparisons for the newer alternatives are not available. We systematically review and compare the three alternative strategies: clopidogrel 600 mg, prasugrel and ticagrelor. A total of 14 studies have compared these strategies with the long-standing convention of 300 mg. Throughout this analysis, we consistently report incremental costs and consequences using clopidogrel 300 mg as the reference strategy. Risk ratios for major adverse cardiovascular events at 30 days were 0.74 (95% confidence interval 0.66-0.82, p=0.002) for clopidogrel 600 mg, 0.78 (0.69-0.89; p<0.001) for prasugrel and 0.88 (0.77-1.00; p=0.045) for ticagrelor. All-cause mortality risk ratios were 0.87 (0.74-1.03) with clopidogrel 600 mg, 0.95 (0.78-1.16) with prasugrel and 0.78 (0.69-0.89) with ticagrelor. TIMI major bleeding has risk ratio 0.92 (0.74-1.16; p=0.85) with clopidogrel 600 mg, 1.32 (1.03-1.16; p=0.03) with prasugrel and 1.25 (1.03-1.53; p=0.03) with ticagrelor. Incremental cost for the first year was £0.32 (US$0.50, €0.40) with clopidogrel 600 mg, £608 (US$977, €709) with prasugrel and £665 (US$1068, €775) with ticagrelor. All three strategies have shown a similar reduction in MACE at 30 days by comparison to clopidogrel 300 mg. All three strategies offer progressive benefit, most marked with Ticagrelor. Whether this is worth both the risk of non-compliance with twice-a-day dosing in real-life patients lacking the same motivation as their trial-volunteer counterparts, and the 2000-fold difference in incremental cost, is the remaining matter for debate.

Topics: Adenosine; Animals; Cardiovascular Diseases; Clopidogrel; Hemorrhage; Humans; Piperazines; Prasugrel Hydrochloride; Thiophenes; Ticagrelor; Ticlopidine

Antiplatelet therapy is used widely with proven benefit for the prevention of further ischemic cardiac complications in patients with known coronary artery disease (CAD) and a history of acute coronary syndrome (ACS). The limitations of conventional antiplatelet therapy with aspirin, clopidogrel, or prasugrel, as well as the fact that rates of recurrent ischemic events still remain high with use of these agents, underscore the need to investigate alternate agents that may further reduce event rates while limiting bleeding risk. The selection of antiplatelet therapy is further influenced by the following: ticagrelor was approved in July 2011 by the United States Food and Drug Administration (FDA), and clopidogrel is slated to become available as a generic productin 2012. We provide an overview of emerging agents for the treatment of CAD and ACS, including the reversible P2Y(12) antagonists ticagrelor, cangrelor, and elinogrel, and a new class of oral protease-activated receptor-1 (PAR-1) inhibitors, vorapaxar and atopaxar.The recently approved P2Y(12) antagonists prasugrel and ticagrelor demonstrate enhanced ability to prevent adverse cardiac outcomes. However, this comes at a cost of a potential increased risk of bleeding. New adverse effects have also emerged, including dyspnea for all of the reversible P2Y(12) antagonists (ticagrelor, cangrelor, and elinogrel) and ventricular pauses for ticagrelor. In addition, the newer P2Y(12) antagonists have a faster onset and offset. Two of these agents, cangrelor and elinogrel, are available as intravenous formulations, which may provide additional benefits in patients who undergo coronary artery bypass graft (CABG) surgery. Trials with the PAR-1 inhibitors have also shown trends toward reductions in cardiac events, but not without the possibility of increased bleeding. More than ever, as the arsenal of antiplatelet therapy expands, health care providers need to understand the pharmacologic and pharmacodynamic differences between conventional and emerging antiplatelet therapies for patients with ACS and CAD. Health care providers must also carefully assess patient-specific factors such as risk of thrombosis, concomitant disease states, age, drug adherence, and aspirin dose, and plan for those patients who will be undergoing CABG when selecting antiplatelet therapy in order to optimally balance bleeding and thrombosis risk.

Topics: Acute Coronary Syndrome; Adenosine; Animals; Clinical Trials as Topic; Coronary Artery Disease; Hemorrhage; Humans; Imines; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyridines; Thiophenes; Thrombosis; Ticagrelor

Antiplatelet treatment is a cornerstone for patients with acute coronary syndromes treated invasively or conservatively to reduce the risk of early and late occurring ischemic complications and to improve survival. Compared to clopidogrel, the novel antiplatelet agents prasugrel and ticagrelor provide faster and more consistent inhibition of platelet aggregation and result in substantially improved clinical outcome in patients with acute coronary syndromes but also an increased bleeding risk. Therefore, balancing the rope between safety and efficacy of treatment is crucial for optimizing outcome. An understanding of the similarities but also differences in pharmacological effect, clinical trial design, and outcome is crucial for understanding which patient populations benefit the most from novel antiplatelet treatments. This review provides recommendations for their optimal use.

Topics: Acute Coronary Syndrome; Adenosine; Hemorrhage; Humans; Myocardial Ischemia; Patient Selection; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor

Platelet inhibitors and anticoagulants are called antithrombotic drugs. New platelet inhibitors prasugrel and ticagrelor are more effective than the traditional clopidogrel, but their use is also accompanied by more frequent bleeding complications. Varfarin has gained true competitors; new oral anticoagulants include dabigatran, rivaroxaban and apixaban. New anticoagulants are easier to use but clearly more expensive. The use of new anticoagulants is also accompanied by several potential problems that the clinician should be aware of.

Topics: Adenosine; Anticoagulants; Benzimidazoles; beta-Alanine; Clopidogrel; Dabigatran; Hemorrhage; Humans; Morpholines; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Ticagrelor; Ticlopidine; Warfarin

Since novel antiplatelet treatments (prasugrel, ticagrelor, high-dose clopidogrel) have been predominantly tested against standard-dose clopidogrel, data on direct comparisons between these therapies are scarce. We therefore indirectly compared their efficacy and safety in patients undergoing percutaneous coronary intervention. Electronic databases were searched systematically to identify head-to-head randomised controlled trials (RCTs). Network meta-analysis was performed using generalised linear mixed models with adjustment for length of follow-up. Findings were corroborated by mixed treatment comparison through Bayesian methods. Fourteen RCTs were identified and included in the analysis (high- vs. standard-dose clopidogrel: 9 trials, prasugrel vs. high-dose clopidogrel: 2 trials, prasugrel vs. standard-dose clopidogrel: 2 trials, ticagrelor vs. standard-dose clopidogrel: 1 trial). No significant differences were found for efficacy outcomes except for stent thrombosis favouring prasugrel (vs. ticagrelor: odds ratio [OR] 0.63, 95% confidence interval [CI]: 0.42, 0.94; vs. high-dose clopidogrel: OR 0.70, 95%CI: 0.48, 1.01). Prasugrel exhibited a similar bleeding risk as high-dose clopidogrel, but more major (OR 1.43, 95%CI 1.07, 1.90) and major or minor bleeding (OR 1.36, 95%CI 1.09, 1.69) compared to ticagrelor. Ticagrelor was also associated with less major or minor bleeding compared to high-dose clopidogrel (OR 0.81, 95%CI 0.69, 0.96). No differences were seen for non CABG-related major bleeding between the three strategies. Results were corroborated in a subgroup analysis comprising only patients with acute coronary syndromes. In the absence of head-to-head clinical trials, network meta-analysis suggests potentially relevant differences in efficacy and bleeding risk among novel antiplatelet treatments and may thereby advance understanding of their differential therapeutic properties.

Topics: Acute Coronary Syndrome; Adenosine; Angioplasty; Cardiovascular Diseases; Clopidogrel; Hemorrhage; Humans; Odds Ratio; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Risk; Stents; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

Anti-platelet agents have left an indelible impression in the management of a wide range of pathologies. From the earliest therapeutic agents such as aspirin, to the cutting edge agents still undergoing development, they have the capability to powerfully manipulate platelet biology, a central player in thrombosis. The use of these agents is still subject to a number of important limitations that two newer agents, prasugrel and ticagrelor, aim to address. Both have recently received licensing for use in acute coronary syndromes and promise to improve outcomes for patients. Here, we examine the rationale for the development and clinical integration of antiplatelet agents focusing upon prasugrel and ticagrelor.

Topics: Acute Coronary Syndrome; Adenosine; Animals; Aspirin; Blood Platelets; Clopidogrel; Drug Design; Hemorrhage; Hemostasis; Humans; Patient Selection; Piperazines; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Factors; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

P2Y12 adenosine di-phosphate (ADP) receptor antagonists are critical to reduce thrombotic recurrences in acute coronary syndromes patients and for those undergoing percutaneous coronary revascularization. Multiple lines of evidence suggest that the level of on-treatment platelet reactivity inhibition with P2Y12 ADP receptor antagonists correlates with thrombotic recurrences. Recent studies observed a relationship between excessive platelet reactivity inhibition and bleedings. Together these data support the potential of platelet reactivity measurement to prevent thrombotic events without increasing bleeding. In the present review we aimed to summarize evidences of a therapeutic window for P2Y12-ADP receptor antagonists and the potential of platelet reactivity monitoring and individualized antiplatelet therapy to optimize the clinical outcome in patients suffering from an acute coronary syndrome or undergoing percutaneous coronary intervention.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Blood Platelets; Clopidogrel; Coronary Thrombosis; Drug Interactions; Drug Resistance; Genotype; Hemorrhage; Humans; Patient Selection; Percutaneous Coronary Intervention; Pharmacogenetics; Phenotype; Piperazines; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Precision Medicine; Predictive Value of Tests; Receptors, Purinergic P2Y12; Risk Assessment; Risk Factors; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

Ticagrelor, an oral P2Y(12) receptor antagonist used as part of dual antiplatelet therapy in the treatment of acute coronary syndromes (ACS), has many favorable characteristics when compared with the more frequently used P2Y(12) receptor antagonist clopidogrel. Ticagrelor binds reversibly, with a rapid onset and offset of action, and produces high levels of platelet inhibition without variation secondary to genetic polymorphism. Ticagrelor produces increased platelet inhibition and an overall reduction in adverse cardiac events compared with clopidogrel. Clinically relevant side effects include an increase in non-CABG-related bleeding events as well as off-target adverse effects including ventricular pauses and dyspnea.. This article details ticagrelor's pharmacokinetic and pharmacodynamic characteristics, development and chemical properties. The authors review relevant clinical trials looking at the efficiency and safety of ticagrelor focusing predominantly on the management of patients with ACS. Finally, the review article concludes with discussion of ticagrelor's current role and future integration into clinical practice.. Ticagrelor is a promising P2Y(12) receptor antagonist with characteristics that offer advantages for patients beyond those currently demonstrated by other P2Y(12) receptor antagonists. The challenge for prescribers is to identify those most likely to benefit from ticagrelor treatment while minimizing unnecessary bleeding events for 'real-world' ACS patients.

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Dyspnea; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine

Ticagrelor is a novel, non-thienopyridine ADP inhibitor that reversibly blocks the P2Y(12) receptor, preventing platelet activation and aggregation. It is the first ADP inhibitor to show a mortality benefit in patients with acute coronary syndromes (ACS). Its major safety concern, as with the other ADP blockers, is bleeding. Other common adverse effects of ticagrelor such as dyspnea and ventricular pauses appear to be mild and self-limited.. The pharmacological properties of ticagrelor compared with clopidogrel are explored in this article. In addition, the relevant clinical trials in which ticagrelor was investigated are described, with an emphasis on efficacy and safety end points.. Although some patients suffer from dyspnea when administered with ticagrelor, there is no evidence of any untoward effects on the cardiovascular or pulmonary systems. Given that the majority of these episodes are mild to moderate and self-limiting, patients should be encouraged to continue the medication, as symptoms may resolve. Furthermore, patients with underlying heart failure or lung disease do not appear to be at an increased risk of developing ticagrelor-induced dyspnea. Its overall mortality benefit among patients with ACS, along with its ability to inhibit platelet aggregation more rapidly and consistently, makes it the preferred agent over clopidogrel.

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Dyspnea; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk Factors; Ticagrelor; Ticlopidine

Despite improved clinical outcomes from dual anti-platelet therapy with aspirin plus the CYP12 ADP receptor antagonist clopidogrel in patients undergoing coronary revascularisation, ex-vivo platelet function testing consistently reveals a proportion of patients with apparent resistance or non-response to clopidogrel loading and maintenance therapy who are at increased risk of coronary thrombosis. Treatment regimens using the newer CYP12 antagonists prasugrel and ticagrelor demonstrate improved ex-vivo platelet inhibition and superior clinical efficacy in large-scale clinical trials-even in patients demonstrating clopidogrel resistance. However, improved efficacy comes at the cost of an increased overall risk of bleeding for both drugs. Further analysis of the outcomes from large scale clinical studies suggests that individual patient sub-groups differ both in their liklehood of bleeding with newer anti-platelet agents and with regard to efficacy outcomes. Therefore when deciding anti-platelet regimens in suspected acute coronary syndrome, particular consideration must be given to patient's risk of thrombosis (STEMI, previous stent thrombosis), the procedure (complex PCI, thrombus in-situ, strategy of pre-treatment), and factors affecting safety (patient age, patient weight, previous stroke, liklehood of surgical revascularisation). Placing the focus on individualised patient risk-benefit assessment with appropriate use of platelet function testing when indicated, in combination with the ongoing assessment of prasugrel and ticagrelor in larger numbers of patients should be the key strategies governing use of dual anti-platelet therapy.

Topics: Adenosine; Animals; Blood Platelets; Cardiovascular Diseases; Clopidogrel; Drug Design; Drug Resistance; Drug Therapy, Combination; Evidence-Based Medicine; Hemorrhage; Humans; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Predictive Value of Tests; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Assessment; Risk Factors; Thiophenes; Ticagrelor; Ticlopidine

This focused update addresses the use of the newly approved oral antiplatelet agents, prasugrel and ticagrelor, for the management of patients with UA/NSTEMI.

Topics: Adenosine; Administration, Oral; Angina, Unstable; Anticoagulants; Evidence-Based Medicine; Hemorrhage; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Assessment; Risk Factors; Thiophenes; Ticagrelor; Treatment Outcome; Warfarin

Despite improvements in the treatment of acute coronary syndromes, cardiovascular disease remains the leading cause of death in Europe and the United States. Antiplatelet agents, such as aspirin and clopidogrel, play an important role in the treatment of those patients. Several new alternatives have been tested in clinical trails and some of them have been approved for routine treatment of patients with ACS in Switzerland and the European Union. The latter include Prasugrel (Efient®) and Ticagrelor (Brilique®). Those substances provide more rapid and consistent platelet inhibition but increase the risk of bleeding in some patient subgroups. Thus, the main challenge is to tailor treatment for each patient by taking into consideration patient characteristics, comorbidities, underlying short- and long-term risk factors, ischemic and bleeding risks, and expected individual responses to different medications. This ambitious new approach will be a challenge for in daily clinical work and may ultimately require prioritization among several treatment alternatives. In this article, we review the new antiplatelet agents being developed as well as their pharmacological characteristics, key interactions and side effects and potential clinical indications in subpopulations.

Topics: Acute Coronary Syndrome; Adenosine; Biological Availability; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Approval; Drug Interactions; Drug Resistance; Drugs, Investigational; Hemorrhage; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Risk Factors; Thiophenes; Ticagrelor

P2Y₁₂, the G(i)-coupled platelet receptor for adenosine diphosphate (ADP), plays a central role in platelet function. Patients with congenital P2Y₁₂ defects display a mild to moderate bleeding diathesis, characterized by mucocutaneous bleedings and excessive post-surgical and post-traumatic blood loss. Defects of P2Y₁₂ should be suspected when ADP, even at high concentrations (≥ 10 μM), is unable to induce full, irreversible platelet aggregation. Tests that evaluate the degree of inhibition of adenylyl cyclase by ADP should be used to confirm the diagnosis. Drugs that inhibit P2Y₁₂ are potent antithrombotic drugs, attesting the central role played by P2Y₁₂ in platelet thrombus formation. Clopidogrel, the most widely used drug that inhibits P2Y₁₂, is effective both in monotherapy and in combination with acetylsalicylic acid. The most important drawback of clopidogrel is its inability to inhibit adequately P2Y₁₂-dependent platelet function in approximately one-third of patients who are therefore not protected from major cardiovascular events. New drugs, such as prasugrel and ticagrelor, which effectively inhibit P2Y₁₂ in the majority of patients, proved to be more efficacious than clopdidogrel in preventing major cardiovascular events. Although they increase the incidence of major bleedings, the net clinical benefit is in favor of the new P2Y₁₂ inhibitors.

Topics: Adenosine; Adenosine Diphosphate; Animals; Blood Platelet Disorders; Blood Platelets; Clopidogrel; Female; Hemorrhage; Humans; Male; Mice; Mutation; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Signal Transduction; Thiophenes; Ticagrelor; Ticlopidine

Inhibiting platelet function is a key therapeutic principle in cardiology because platelets play a pivotal role in triggering cardiovascular events. In addition to acetylsalicylic acid, a cyclooxygenase inhibitor, ADP-receptor blockers are frequently used for anti-platelet therapy. This therapy does not abolish platelet activation and aggregation. Platelets may still be activated by alternative routes such as the thrombin receptor-mediated pathway. New, more potent inhibitors of platelet function continue to lower the risk of ischaemic events but several trials and clinical registries have also shown that this advantage was frequently offset by an increased risk of bleeding complications. As a consequence, the individual risk of ischaemia and bleeding of a patient must be taken into consideration to select the platelet inhibitor offering the best benefit-risk ratio. Modern laboratory diagnostics may help to achieve this goal by complementing functional platelet tests with pharmacogenomic analyses consistent with the idea of "personalized medicine".

Topics: Acute Coronary Syndrome; Adenosine; Adenosine Monophosphate; Aspirin; Clopidogrel; Coronary Thrombosis; Drug Interactions; Hemorrhage; Humans; Piperazines; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Ticlopidine

P2Y12, one of the two platelet receptors for adenosine diphosphate (ADP), plays a central role in platelet function. Defects of P2Y12 should be suspected when ADP, even at high concentrations (≥10 µM), is unable to induce full, irreversible platelet aggregation. Patients with congenital P2Y12 defects display a mild-to-moderate bleeding diathesis of variable severity, characterised by mucocutaneous bleeding and excessive post-surgical and post-traumatic blood loss. Drugs that inhibit P2Y12 are potent antithrombotic drugs, attesting the central role played by P2Y12 in platelet thrombus formation. Clopidogrel, the most widely used drug that inhibits P2Y12, is effective both in monotherapy and in combination with acetylsalicylic acid (ASA). Its most important drawback is the inability to inhibit adequately P2Y12-dependent platelet function in about 1/3 of patients, at the recommended therapeutic doses. The incidence of bleeding events is similar in ASA-treated and clopidogrel-treated patients; however, the combination of ASA and clopidogrel causes more bleeding than each drug in monotherapy. Compared to clopidogrel, new drugs inhibiting P2Y12, such as prasugrel and ticagrelor, decrease the risk of cardiovascular events and increase the risk of bleeding complications, because they adequately inhibit P2Y12-dependent platelet function in the vast majority of treated patients.

Topics: Adenosine; Adenosine Diphosphate; Adenosine Monophosphate; Animals; Clinical Trials, Phase III as Topic; Clopidogrel; Hemorrhage; Humans; Piperazines; Platelet Activation; Prasugrel Hydrochloride; Quinazolinones; Receptors, Purinergic P2Y12; Sulfonamides; Thiophenes; Ticagrelor; Ticlopidine

Thienopyridines have become the cornerstone of treatment of percutaneous coronary intervention although no survival benefit has ever been shown with clopidogrel despite increasing loading doses. Newly developed P2Y(12) inhibitors are more potent, more predictable and have a faster onset of action than clopidogrel, characteristics that make them particularly attractive for high-risk PCI. Four new P2Y(12) inhibitors have been tested each of them having particular individual properties. Prasugrel is an oral prodrug leading to irreversible blockade of the P2Y(12) receptor and is approved worldwide for ACS PCI. Ticagrelor is a direct-acting and reversible inhibitor of the P2Y(12) receptor with potentially more pleiotropic effects. Cangrelor is an intravenous direct and reversible inhibitor of the P2Y(12) receptor providing the highest level of inhibition and elinogrel is an intravenous and oral P2Y(12) antagonist with a direct and reversible action. Both prasugrel and ticagrelor, opposed to clopidogrel, have shown that stronger P2Y(12) inhibition led respectively to significant 19 % and 16 % relative risk reduction of a similar primary endpoint combining cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Both drugs showed a significant 0.6 % absolute excess of TIMI major bleeding not related to CABG surgery. The effect of these new compounds is prompt, predictable and powerful as compared to clopidogrel. Their net benefit is particularly marked in PCI for STEMI patients, in which there is no significant increase in major bleeding when compared with clopidogrel. However, because in clinical trials patients perceived to be at higher risk for bleeding usually are excluded, the risk of major and even fatal bleeding might even be higher in a "real-world" setting i.e. in the elderly patient with comorbidities.

Topics: Adenosine; Adenosine Monophosphate; Administration, Oral; Clinical Trials as Topic; Clopidogrel; Combined Modality Therapy; Disease Management; Drug Resistance; Fibrinolytic Agents; Hemorrhage; Humans; Injections, Intravenous; Multicenter Studies as Topic; Myocardial Infarction; Myocardial Reperfusion; Myocardial Revascularization; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Thiophenes; Ticagrelor; Ticlopidine; Time Factors

Platelets play a pivotal role in the pathogenesis of acute coronary syndromes (ACS) and their inhibition remains a mainstay therapy in this setting. We aimed to perform a meta-analysis of randomized trials to evaluate the benefits of new oral antiplatelet regimens to block platelet ADP-receptors compared to standard-dose clopidogrel (300 mg loading dose followed by 75 mg/daily).. We obtained results from all randomized trials enrolling patients with ACS. Primary endpoint was mortality. Secondary endpoints were myocardial infarction and definite in-stent thrombosis. Safety endpoint was the risk of major bleeding complications. We prespecified subanalyses according to new antiplatelet drugs (prasugrel/ticagrelor), high-dose clopidogrel (600 mg) and patients undergoing percutaneous coronary intervention.. A total of seven randomized trials were finally included in the meta-analysis (n = 58 591). We observed a significant reduction in mortality (2.9% vs. 3.4%, OR = 0.87, 95% CI 0.79-0.95, P = 0.002), recurrent myocardial infarction (4.2% vs. 5.2%, OR = 0.80, 95% CI 0.74-0.87, P < 0.0001), definite in-stent thrombosis (0.9% vs. 1.7%, OR = 0.52, 95% CI 0.43-0.63, P < 0.0001). The benefits in mortality and reinfarction were driven by the treatment with prasugrel or ticagrelor, without a significant difference in terms of major bleeding complications as compared to standard-dose clopidogrel (5% vs. 4.7%, OR = 1.06 95% CI 0.96-1.17, P = 0.25).. This meta-analysis showed that new oral antiplatelet regimens are associated with a significant reduction in mortality, reinfarction and in-stent thrombosis in ACS patients without an overall increase of major bleeding when treated with new antiplatelet drugs.

Topics: Acute Coronary Syndrome; Adenosine; Administration, Oral; Clopidogrel; Hemorrhage; Humans; Ischemia; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Thiophenes; Ticagrelor; Ticlopidine

Various definitions of major bleeding have been used to evaluate safety in randomized controlled trials of antiplatelet therapy. We compared the definitions and rates of major bleeding in phase III randomized controlled trials of oral P2Y(12) inhibitors in the management of patients with acute coronary syndromes (ACS).. Electronic searches identified six phase III randomized controlled oral P2Y(12) inhibitor trials published between 2001 and 2010 involving 119 020 patients with ACS. The trials compared clopidogrel standard-dose (300-mg loading dose, 75-mg daily thereafter) vs. placebo (CURE, CLARITY-TIMI 28, COMMIT), clopidogrel standard-dose vs. prasugrel (TRITON-TIMI 38) or ticagrelor (PLATO) and clopidogrel standard-dose vs. clopidogrel double-dose (600-mg loading dose, 150-mg daily for 6-days, 75-mg daily thereafter) (CURRENT-OASIS 7). Using the trial definition, major bleeding rates in patients treated with standard-dose clopidogrel ranged from 0.6% in COMMIT to 11.2% in PLATO. The contrast in bleeding rates of standard-dose clopidogrel among the trials was attenuated when using the thrombolysis in myocardial infarction (TIMI) definition for major bleeding (range 1.1-7.7%) and bleeding rates in all the trials were less than 2% when comparing 30 day rates of non-coronary artery bypass graft surgery-related TIMI major bleeding (range 0.3-1.9%).. Differences in major bleeding rates between trials of P2Y(12) inhibitors in patients with ACS are minimized after standardization of bleeding definitions, timing of reporting of bleeding outcomes, and procedure rates. Interpretation of the risk of bleeding associated with different P2Y(12) inhibitors would be facilitated by a consistent approach to the definition and reporting of bleeding.

Topics: Acute Coronary Syndrome; Adenosine; Clinical Trials, Phase III as Topic; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Piperazines; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Factors; Thiophenes; Ticagrelor; Ticlopidine

Acute coronary syndromes (ACS) are still associated with significant morbidity and mortality. Dual antiplatelet therapy with clopidogrel and acetyl-salicylic acid has become the standard of care for patients with ACS in the last 2 decades. However, clopidogrel has drawbacks including delayed therapeutic effect, significant interindividual variability of platelet aggregation inhibition or reduced action on thrombocytes due to interaction with other drugs or genetic polymorphisms. Consequently, new antiplatelet drugs have been developed. Two of these drugs, namely prasugrel and ticagrelor, have been approved by the European Medicines Agency (EMA) and are already available in many European countries. For each substance a "mega-trial" has been published. Both agents were clearly superior compared to clopidogrel and should be therefore preferred in patients with ACS. However, no study has directly compared efficacy as well as safety of prasugrel and ticagrelor so far. Hence, clinicians will be claimed to decide which one to choose in everyday practice. The aim of this manuscript is to summarize the current literature and to provide a guide for individual decision-making between prasugrel and ticagrelor in ACS in daily routine.

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Hemorrhage; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Factors; Survival Rate; Thiophenes; Ticagrelor; Ticlopidine

Current guidelines recommend dual antiplatelet therapy, a combination of aspirin and a P2Y(12) inhibitor, for 6?12 months after percutaneous coronary intervention with drug-eluting stent implantation in all patients and for 1 year in all patients after an acute coronary syndrome (ACS), irrespective of revascularization strategy. Clopidogrel has a pharmacokinetic and pharmacodynamic profile that results in a delayed and/or subtherapeutic antiplatelet effect, and wide variability in antiplatelet response. New P2Y(12) inhibitors, such as prasugrel and ticagrelor, have favorable pharmacodynamics and clinical efficacy over clopidogrel and offer an alternative antiplatelet treatment strategy in specific patients. Prasugrel has more potent, rapid, and consistent effects on inhibiting ADP-induced platelet aggregation than clopidogrel. Ticagrelor also appears to have more rapid and consistent antiplatelet effects than clopidogrel. The higher levels of antiplatelet inhibition provided by prasugrel and ticagrelor compared with standard-dose clopidogrel result in improved ischemic outcomes in patients with ACS. Despite an increase in bleeding risk, prasugrel and ticagrelor appear to have a better net clinical benefit, especially in higher-risk patients with ACS.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Piperazines; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Risk Factors; Secondary Prevention; Thiophenes; Ticagrelor; Ticlopidine

Chronic kidney disease (CKD) is prevalent and affects an ever-increasing proportion of patients presenting with acute coronary syndrome (ACS). Patients with CKD have a higher risk of ACS and significantly higher mortality, and are also predisposed to increased bleeding complications. Antiplatelet and antithrombotic drugs form the bedrock of management of patients with ACS. Most randomized trials of these drugs exclude patients with CKD, and current guidelines for management of these patients are largely based on these trials. We aim to review the safety and efficacy of these drugs in patients with CKD presenting with ACS.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Chronic Disease; Clinical Trials as Topic; Clopidogrel; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; Kidney Diseases; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Prasugrel Hydrochloride; Recombinant Proteins; Thiophenes; Ticagrelor; Ticlopidine; Uremia

Antithrombotic therapy constitutes the basis of the management of acute coronary syndromes. It combines antiplatelet and anticoagulant therapy. Antiplatelet agents should combine aspirin and agents acting through the ADP pathway such as clopidogrel; newer antiplatelet agents such as prasugrel or ticagrelor have superior anti-ischemic efficacy, compared with clopidogrel. Intravenous glycoprotein IIb/IIIa inhibitors may be used in selected patients at high risk undergoing percutaneous coronary interventions. Unfractionated heparin constitutes the reference anticoagulant treatment. Enoxaparin provides slightly better anti-ischemic efficacy. Newer agents, such as bivalirudin or fondaparinux, reduce bleeding complications, with no improvement in anti-ischemic efficacy. The combination of antiplatelet and anticoagulant agents should be chosen according to the patients' characteristics and the management strategy of the acute coronary syndrome.

Topics: Acute Coronary Syndrome; Adenosine; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Disease Management; Drug Synergism; Drug Therapy, Combination; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Recombinant Proteins; Thiophenes; Ticagrelor; Ticlopidine

Antiplatelet agents play an essential role in the treatment of acute coronary syndrome (ACS). Thienopyridines are a class of drugs that function via inhibition of the adenosine diphosphate (ADP) P2Y12 platelet receptors. Currently, clopidogrel, a second generation thienopyridine, is the main drug of choice and the combination of aspirin and clopidogrel is administered orally for the treatment of ACS. Clopidogrel, is a pro-drug that needs to be metabolized in the liver and intestines to form active metabolites. Prasugrel, a third generation thienopyridine, was approved for use in Europe in February 2009, and is currently available in the United Kingdom. All thienopyridines however, have pharmacological limitations that lead to a search for more effective non-thienopyridine P2Y12 inhibitors. Promising results have been reported with ticagrelor, an oral first reversible, direct-acting inhibitor of the P2Y12 receptor. Ticagrelor is the first oral P2Y12 receptor binding antagonist that does not require metabolic activation. Furthermore, ticagrelor has at last 1 active metabolite, which has very similar pharmacokinetics to the parent compound. Therefore, ticagrelor has more rapid onset and more pronounced platelet inhibition than other antiplatelet agents. The safety and efficacy of ticagrelor compared with clopidogrel in ACS patient has been recently evaluated by the PLATelet inhibition and patient Outcomes (PLATO) trial. Ticagrelor compared with clopidogrel had a significantly greater reduction in the death rate from vascular causes, myocardial infarction, or stroke without major bleeding. There was however, an increase in non-procedure related bleeding, dyspnoea and ventricular pauses in the first week of treatment. Further studies on new antiplatelet agents are needed to establish a new "gold standard" antiplatelet therapy.

Topics: Acute Coronary Syndrome; Adenosine; Adenosine Monophosphate; Biotransformation; Clinical Trials as Topic; Clopidogrel; Hemorrhage; Humans; Lactones; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Pyridines; Receptors, Purinergic P2; Receptors, Purinergic P2Y12; Thiophenes; Ticagrelor; Ticlopidine

Current guidelines recommend a standard ticagrelor loading dose (LD) in ST-segment elevation myocardial infarction (STEMI) patients. However, antiplatelet therapy in STEMI patients at high risk of thrombotic events is suboptimal. The study was conducted to validate whether vasodilatorstimulated phosphoprotein (VASP)-guided ticagrelor dosing individual therapy may result in more effective platelet inhibition and better clinical outcomes.. This trial included 374 STEMI patients with a low platelet response after ticagrelor LD. The patients were randomized into a control group and a VASP-guided group, where the ticagrelor pretreatment was individually adjusted before and after percutaneous coronary intervention (PCI) to obtain a VASP index < 50%. Up to 2 additional boluses of ticagrelor (every additional dosing was 90 mg) were prescribed after the first LD, and the VASP index was assessed 2 hours after each administration until a VASP index < 50% was obtained or up to 3 dosages (360 mg). The primary endpoint was major adverse cardiovascular events (MACEs) at 30 days. The secondary endpoints were thrombolysis in myocardial infarction (TIMI) major and minor bleeding.. The characteristics were similar in the two groups. After the ticagrelor doses increased, the platelet reactivity index (PRI) decreased, and 98.4% of patients reached PRI < 50% in the VASP-guided group. The adenosine concentration increased, and the rate of MACE was significantly lower in the VASP-guided group (10 [5.3%] vs. 20 [10.8%], hazard ratio 2.38, 95% confidence interval 1.21-3.28, p = 0.007). There were no major hemorrhagic complications (0 vs. 0, p = 1.0). The rate of minor bleeding in the VASP-guided group was higher than that in the control group, but the difference was not significant (24 [12.8%] vs. 16 [8.6%], p = 0.068).. The incremental ticagrelor dosing strategy decreases the rate of MACE after PCI without increasing major and minor bleeding.

Topics: Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Phosphoproteins; Phosphorylation; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Elderly status is steadily increasing among patients with acute coronary syndrome (ACS). Dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 receptor inhibitor is the cornerstone of treatment to prevent recurrent thrombotic complications in patients with ACS. However, DAPT in older patients is challenged by a concurrent heightened risk of ischemia and bleeding. The aim of this study is to evaluate the pharmacodynamic and pharmacokinetic profile of a lower dose of ticagrelor (60 mg twice daily) among elderly patients during the early phase of ACS.. PLINY THE ELDER (PLatelet INhibition with two different doses of potent P2y12 inhibitors in THE ELDERly population) (NCT04739384) is a prospective, randomized, open-label, crossover trial to evaluate the non-inferiority of a lower dose of ticagrelor (60 mg twice daily) compared with a standard dose (90 mg twice daily) among elderly patients with ACS undergoing percutaneous coronary intervention (PCI). A total of 50 patients, aged 75 years or more, with indication to potent P2Y12 receptor inhibitors will be randomized within 3 days from PCI for the index ACS. Patients with indication to oral anticoagulant therapy, treatment with glycoprotein IIb/IIIa inhibitors, or active bleeding will be excluded. The primary endpoint is platelet reactivity determined by P2Y12 reaction units (PRU) (VerifyNow, Accumetrics, San Diego, CA, USA) after treatment with ticagrelor 60 or 90 mg twice daily for 14 days. Secondary endpoints will include other pharmacodynamic tests of ADP-induced aggregation (light transmittance aggregometry and multiple electrode aggregometry) and determination of pharmacokinetic profile (plasma levels of ticagrelor and its metabolite AR-C124910XX) by high performance liquid chromatography-tandem mass spectrometry.. The PLINY THE ELDER trial will determine whether a lower dose of ticagrelor confers non-inferior platelet inhibition compared with the standard dose in the early phase of ACS among elderly patients undergoing PCI, informing future clinical investigation.

Topics: Acute Coronary Syndrome; Aged; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

To assess the efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndrome (ACS) presenting during off- and on-hours.. The efficacy and safety of ticagrelor versus prasugrel in patients with ACS according to time of hospital presentation remain unknown.. This post hoc analysis of the ISAR-REACT 5 trial included 1565 patients with ACS presenting off-hours and 2453 patients presenting on-hours, randomized to ticagrelor or prasugrel. The primary endpoint was a composite of death, myocardial infarction, or stroke; the safety endpoint was Bleeding Academic Research Consortium (BARC) type 3-5 bleeding, both at 12 months.. In patients with ACS planned to undergo an invasive treatment strategy, time of presentation (off-hours vs. on-hours) does not interact significantly with the relative efficacy and safety of ticagrelor vs. prasugrel.. NCT01944800.

Topics: Acute Coronary Syndrome; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor; Treatment Outcome

There is limited evidence on the association of sex with outcomes among patients undergoing coronary bypass surgery (CABG) and treated with ticagrelor monotherapy or aspirin.. This was a pre-specified sub-analysis of TiCAB, an investigator-initiated placebo-controlled randomized trial. Primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction, stroke, or repeat revascularization 1 year after CABG. Safety endpoint was BARC type 2, 3 or 5 bleeding.. Among women and men undergoing CABG, ticagrelor monotherapy was associated with a similar risk of the primary efficacy endpoint and bleeding compared with aspirin. The risk of cardiovascular death was increased in women irrespective of antiplatelet therapy.

Topics: Aspirin; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Sex Characteristics; Ticagrelor; Treatment Outcome

The effect of a prasugrel vs. a ticagrelor based strategy on total (including both first and recurrent) ischaemic and bleeding events in patients with acute coronary syndromes (ACS) has not been evaluated. The aim of this analysis was to investigate the treatment effect of a prasugrel vs. a ticagrelor based strategy in patients with ACS undergoing an invasive management strategy when both first and recurrent non-fatal ischaemic and bleeding events are taken into account.. This is a post-hoc analysis of the ISAR-REACT 5 randomized control trial, including all 4018 patients in the trial. The main clinical endpoints of interest included ischaemic events [myocardial infarction (MI) and stroke] and bleeding events [Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding]. An additional endpoint of interest was definite/probable stent thrombosis. The effect of the prasugrel vs. ticagrelor based strategies on these endpoints was evaluated on both time-to-first event and total events analyses. Patients in the prasugrel group had a lower risk of MI in comparison to the ticagrelor group on both time-to-first event [hazard ratio (HR) = 0.61; 95% confidence interval 0.44-0.85] and total events [HR = 0.62 (0.45-0.86)] analysis. The risk of BARC type 3 to 5 bleeding was comparable between the prasugrel and ticagrelor groups on both time-to-first event [HR = 0.96 (0.75-1.25)] and total events [HR = 0.99 (0.76-1.31)] analysis.. A prasugrel based strategy was associated with a reduction in total MI events in comparison to a ticagrelor based strategy in patients with ACS undergoing invasive assessment. Total BARC type 3 to 5 bleeding events were comparable between the two groups. Given the importance of this topic, future studies to confirm these findings would be welcome. ClinicalTrials.gov identifier: NCT01944800.

Topics: Acute Coronary Syndrome; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor

This study was performed to investigate whether ticagrelor/aspirin versus clopidogrel/aspirin can further reduce the residual risk of stroke recurrence in patients with positive diffusion-weighted imaging (DWI) in the High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial.. Patients with DWI data in the CHANCE-2 trial were included and divided into those with and without acute infarction according to their DWI findings. The primary efficacy outcome and safety outcome were stroke recurrence and moderate to severe bleeding within 3 months of follow-up, respectively.. Of the 6,412 patients enrolled in the CHANCE-2 trial, 5,796 (90.4%) patients with DWI data were included in the subgroup analysis. A total of 4,369 patients (75.4%) had an acute infarction on DWI. Patients with positive DWI had higher risk of recurrent stroke (8.1%) than those without infarction (2.2%) within 3-month follow-up. Compared with clopidogrel/aspirin, ticagrelor/aspirin was associated with lower risk of stroke in patients with positive DWI (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.52-0.80, p < 0.001) than in those negative DWI (HR = 1.22, 95% CI = 0.55-2.72, p = 0.63), with a significant interaction association (p for interaction = 0.049). The risk of moderate to severe bleeding was similar between ticagrelor/aspirin and clopidogrel/aspirin treatment in the different groups.. Our study demonstrates that imaging evaluation should be emphasized before targeting the best candidates for genotype-guided dual antiplatelet therapy in future clinical research and practice. ANN NEUROL 2023;93:783-792.

Topics: Aspirin; Cerebral Infarction; Clopidogrel; Drug Therapy, Combination; Genotype; Hemorrhage; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

The aim of this study was to assess the effect of ticagrelor monotherapy among high-risk patients with anaemia undergoing percutaneous coronary intervention (PCI).. In the TWILIGHT (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, after 3 months of ticagrelor plus aspirin, high-risk patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. Anaemia was defined as haemoglobin <13 g/dL for men and <12 g/dL for women. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction, or stroke.Out of 6828 patients, 1329 (19.5%) had anaemia and were more likely to have comorbidities, multivessel disease, and to experience bleeding or ischaemic complications than non-anaemic patients. Among anaemic patients, BARC 2, 3, or 5 bleeding occurred less frequently with ticagrelor monotherapy than with ticagrelor plus aspirin [6.4% vs. 10.7%; hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.41-0.88; P = 0.009]; the rate of the key secondary endpoint was similar in the two arms (5.2% vs. 4.8%; HR 1.07; 95% CI 0.66-1.74; P = 0.779). These effects were consistent in patients without anaemia (interaction P values 0.671 and 0.835, respectively).. In high-risk patients undergoing PCI, ticagrelor monotherapy after 3 months of ticagrelor-based dual antiplatelet therapy was associated with a reduced risk of clinically relevant bleeding without any increase in ischaemic events irrespective of anaemia status (TWILIGHT: NCT02270242).

Topics: Anemia; Aspirin; Female; Hemorrhage; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor

It is unclear whether infarct location affects stroke recurrence after index ischemic stroke. We aimed to compare the risk of stroke recurrence and the responses to dual antiplatelets with ticagrelor-aspirin versus clopidogrel-aspirin between patients with posterior circulation infarct (PCI) and those with anterior circulation infarct (ACI) after minor stroke or transient ischemic attack.. Data were obtained from the double-blind CHANCE-2 trial (Ticagrelor or Clopidogrel With Aspirin in High-Risk Patients With Acute Nondisabling Cerebrovascular Events II), which was conducted across 202 centers in China from September 2019 to March 2021. Patients with positive diffusion-weighted imaging were included and classified into PCI and ACI groups according to the hyperintense lesions on diffusion-weighted imaging. The primary efficacy and safety outcomes were a new stroke and severe or moderate bleeding within 90 days, respectively.. A total of 4168 patients were included in this substudy, with 1427 PCI and 2741 ACI. During the 90-day follow-up, the risk of stroke recurrence in patients with PCI was similar to that with ACI (7.4% versus 8.3%; adjusted hazard ratio, 1.01 [95% CI, 0.79-1.29];. Our study demonstrated that stroke recurrence was similar between PCI and ACI in patients with minor stroke or transient ischemic attack. Additionally, ticagrelor-aspirin was superior to clopidogrel-aspirin in reducing the risk of stroke within 90 days in both PCI and ACI patients.. URL: https://www.. gov; Unique identifier: NCT04078737.

Topics: Aspirin; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Infarction; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

We sought to explore the sex differences in clinical outcomes among patients with acute coronary syndrome treated with ticagrelor monotherapy after ticagrelor-based 3-month versus 12-month dual-antiplatelet therapy.. This was a post hoc analysis of the TICO trial (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus-Eluting Stent for Acute Coronary Syndrome; n=3056)-a randomized controlled trial for patients with acute coronary syndrome treated with drug-eluting stent. The primary outcome was a net adverse clinical event (composite of major bleeding, death, myocardial infarction, stent thrombosis, stroke, or target-vessel revascularization) 1 year after drug-eluting stent implantation. Secondary outcomes included major bleeding and major adverse cardiac and cerebrovascular events.. There were 27.3% (n=628) women in the TICO trial; they were older with lower body mass index and higher prevalence of hypertension, diabetes, or chronic kidney disease than men. Compared with men, women had higher risk of net adverse clinical events (hazard ratio [HR], 1.89 [95% CI, 1.34-2.67]), major adverse cardiac and cerebrovascular events (HR, 1.69 [95% CI, 1.07-2.68]), and major bleeding (HR, 2.04 [95% CI, 1.25-3.35]). Among the groups stratified by sex and dual-antiplatelet therapy strategy, the incidences of primary and secondary outcomes were significantly different and the highest in women with ticagrelor-based 12-month dual-antiplatelet therapy (. After percutaneous coronary intervention for acute coronary syndrome, women demonstrated worse clinical outcomes than men. Ticagrelor monotherapy after 3-month dual-antiplatelet therapy was associated with significantly lower risk of net adverse clinical events in women without sex interaction.

Topics: Acute Coronary Syndrome; Aspirin; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Sex Characteristics; Ticagrelor

About 5%-15% of acute coronary syndrome (ACS) patients undergoing stent implantation have concomitant atrial fibrillation and need both antiplatelet and anticoagulant therapies. The optimal antithrombotic regimen remains uncertain in this scenario.. A multicenter randomized controlled trial (OPtimal management of anTIthroMbotic Agents [OPTIMA]-4) is designed to test the hypothesis that, for ACS patients with concomitant nonvalvular atrial fibrillation (NVAF) and having low-to-moderate risk of bleeding, clopidogrel is comparable in efficacy but superior in safety compared to ticagrelor while being used in combination with dabigatran after new-generation drug-eluting stent (DES) implantation.. ACS patients who have low-to-moderate risk of bleeding (e.g., HAS-BLED score ≤ 2) and require anticoagulation therapy (CHA. The first enrollment occurred on March 12, 2018. The recruitment is anticipated to be completed before December 31, 2024.. The OPTIMA-4 trial offers an opportunity to assess the optimal dual antithrombotic regimen in ACS patients with concomitant NVAF after the implantation of new-generation DES.

Topics: Acute Coronary Syndrome; Aspirin; Atrial Fibrillation; Clopidogrel; Dabigatran; Drug Therapy, Combination; Drug-Eluting Stents; Fibrinolytic Agents; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor

Platelet activation is a potential therapeutic target in patients with COVID-19.. To evaluate the effect of P2Y12 inhibition among critically ill patients hospitalized for COVID-19.. This international, open-label, adaptive platform, 1:1 randomized clinical trial included critically ill (requiring intensive care-level support) patients hospitalized with COVID-19. Patients were enrolled between February 26, 2021, through June 22, 2022. Enrollment was discontinued on June 22, 2022, by the trial leadership in coordination with the study sponsor given a marked slowing of the enrollment rate of critically ill patients.. Participants were randomly assigned to receive a P2Y12 inhibitor or no P2Y12 inhibitor (usual care) for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor.. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death and, for participants who survived to hospital discharge, the number of days free of cardiovascular or respiratory organ support up to day 21 of the index hospitalization. The primary safety outcome was major bleeding, as defined by the International Society on Thrombosis and Hemostasis.. At the time of trial termination, 949 participants (median [IQR] age, 56 [46-65] years; 603 male [63.5%]) had been randomly assigned, 479 to the P2Y12 inhibitor group and 470 to usual care. In the P2Y12 inhibitor group, ticagrelor was used in 372 participants (78.8%) and clopidogrel in 100 participants (21.2%). The estimated adjusted odds ratio (AOR) for the effect of P2Y12 inhibitor on organ support-free days was 1.07 (95% credible interval, 0.85-1.33). The posterior probability of superiority (defined as an OR > 1.0) was 72.9%. Overall, 354 participants (74.5%) in the P2Y12 inhibitor group and 339 participants (72.4%) in the usual care group survived to hospital discharge (median AOR, 1.15; 95% credible interval, 0.84-1.55; posterior probability of superiority, 80.8%). Major bleeding occurred in 13 participants (2.7%) in the P2Y12 inhibitor group and 13 (2.8%) in the usual care group. The estimated mortality rate at 90 days for the P2Y12 inhibitor group was 25.5% and for the usual care group was 27.0% (adjusted hazard ratio, 0.96; 95% CI, 0.76-1.23; P = .77).. In this randomized clinical trial of critically ill participants hospitalized for COVID-19, treatment with a P2Y12 inhibitor did not improve the number of days alive and free of cardiovascular or respiratory organ support. The use of the P2Y12 inhibitor did not increase major bleeding compared with usual care. These data do not support routine use of a P2Y12 inhibitor in critically ill patients hospitalized for COVID-19.. ClinicalTrials.gov Identifier: NCT04505774.

Topics: COVID-19; Critical Illness; Hemorrhage; Hospital Mortality; Humans; Male; Middle Aged; Purinergic P2Y Receptor Agonists; Ticagrelor

The Clopidogrel With Aspirin in High-Risk Patients With Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial showed that ticagrelor-aspirin combination therapy reduced the risk of stroke compared with a clopidogrel-aspirin combination among carriers of CYP2C19 loss-of-function (LOF) alleles after a transient ischemic attack (TIA) or minor ischemic stroke. However, the association between the degree of CYP2C19 LOF and ideal treatment allocation remains unknown.. To investigate whether the efficacy and safety of ticagrelor-aspirin vs clopidogrel-aspirin are consistent with the expected degree of CYP2C19 LOF after TIA or minor stroke.. CHANCE-2 was a multicenter, double-blind, double-dummy, placebo-controlled randomized clinical trial. Patients were enrolled at 202 centers in China from September 23, 2019, through March 22, 2021. Patients with at least two *2 or *3 alleles (*2/*2, *2/*3, or *3/*3) according to point-of-care genotyping were classified as "poor metabolizers," and those with one *2 or *3 allele (*1/*2 or *1/*3) were classified as "intermediate metabolizers.". Patients were randomly assigned in a 1:1 ratio to receive ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily for days 2-90) or clopidogrel (300-mg loading dose on day 1 followed by 75 mg/d for days 2-90). All patients received aspirin (75- to 300-mg loading dose followed by 75 mg/d for 21 days).. The primary efficacy outcome was a new ischemic or hemorrhagic stroke. The secondary efficacy outcome was a composite of new clinical vascular events and individual ischemic stroke events within 3 months. The primary safety outcome was severe or moderate bleeding. Analyses were performed according to the intention-to-treat principle.. Of the 6412 patients enrolled, the median age was 64.8 years (IQR, 57.0-71.4 years), and 4242 patients (66.2%) were men. Of the 6412 patients, 5001 (78.0%) were intermediate metabolizers, and 1411 (22.0%) were poor metabolizers. The primary outcome occurred less often with ticagrelor-aspirin vs clopidogrel-aspirin, irrespective of metabolizer status (6.0% [150 of 2486] vs 7.6% [191 of 2515]; hazard ratio [HR], 0.78 [95% CI, 0.63-0.97] among intermediate metabolizers and 5.7% [41 of 719] vs 7.5% [52 of 692]; HR, 0.77 [95% CI, 0.50-1.18] among poor metabolizers; P = .88 for interaction). Patients taking ticagrelor-aspirin had a higher risk of any bleeding event compared with those taking clopidogrel-aspirin, irrespective of metabolizer status: 5.4% (134 of 2486) vs 2.6% (66 of 2512) (HR, 2.14 [95% CI, 1.59-2.89]) among intermediate metabolizers and 5.0% (36 of 719) vs 2.0% (14 of 692) (HR, 2.99 [95% CI, 1.51-5.93]) among poor metabolizers (P = .66 for interaction).. This prespecified analysis of a randomized clinical trial found no difference in treatment effect between poor and intermediate CYP2C19 metabolizers. The relative clinical efficacy and safety of ticagrelor-aspirin vs clopidogrel-aspirin were consistent across CYP2C19 genotypes.. ClinicalTrials.gov Identifier: NCT04078737.

Topics: Aged; Aspirin; Clopidogrel; Cytochrome P-450 CYP2C19; East Asian People; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Male; Middle Aged; Platelet Aggregation Inhibitors; Stroke; Ticagrelor

Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free single antiplatelet therapy (SAPT) strategy with a potent P2Y

Topics: Acute Coronary Syndrome; Aspirin; Drug Therapy, Combination; Drug-Eluting Stents; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor; Treatment Outcome

Body mass index (BMI) may affect the response to platelet P2Y. In a multicentre, randomized, double-blind, placebo-controlled trial, conducted in China, we randomized patients with minor stroke or TIA who carried the. Among 6412 patients, 876 were classified as obese and 5536 were classified as nonobese. Compared with clopidogrel-ASA, ticagrelor-ASA was associated with a significantly lower rate of stroke within 90 days among patients with obesity (25 [5.4%] v. 47 [11.3%]; hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.30-0.87), but not among those in the nonobese group (166 [6.0%] v. 196 [7.0%]; HR 0.84, 95% CI 0.69-1.04) The interaction of treatment and BMI group was significant (. In this secondary analysis of a randomized controlled trial involving patients with minor ischemic stroke or TIA, compared with clopidogrel-ASA, patients with obesity received more clinical benefit from ticagrelor-ASA therapy than those without obesity.. Clinicaltrials.gov, no. NCT04078737.

Topics: Aspirin; Body Mass Index; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Obesity; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

In TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention), among high-risk patients undergoing percutaneous coronary intervention (PCI), ticagrelor monotherapy vs continuation of dual antiplatelet therapy (DAPT) with aspirin and ticagrelor after completing a 3-month course of DAPT was associated with reduced bleeding, without an increase in ischemic events.. This investigation sought to study the clinical benefit of ticagrelor monotherapy vs DAPT by simultaneously modeling its associated potential bleeding benefits and ischemic harms on an individual patient basis.. Multivariable Cox regression models for: 1) Bleeding Academic Research Consortium type 2, 3, or 5 (BARC-2/3/5); and 2) cardiovascular death, nonfatal myocardial infarction, and nonfatal ischemic stroke (major adverse cardiac and cerebrovascular event [MACCE]) were developed using stepwise forward variable selection. The coefficients in the BARC-2/3/5 and MACCE models were used to calculate bleeding and ischemic risk scores, respectively, for each patient (excluding the coefficient for randomized treatment).. In the total study group (N = 7,119), BARC-2/3/5 occurred in 391 (5.5%) patients, and MACCE occurred in 258 (3.6%). There was a consistent reduction in bleeding events associated with ticagrelor monotherapy compared with DAPT across both bleeding and ischemic risk strata (P interaction = 0.54 and 0.11, respectively). Importantly, this benefit associated with ticagrelor monotherapy was not offset by an increase in MACCE at any level of bleeding or ischemic risk.. Three months after PCI, discontinuing aspirin and maintaining ticagrelor monotherapy reduces bleeding in both higher-bleeding risk and lower-bleeding risk patients compared with continued DAPT. This benefit does not appear to be offset by greater ischemic risk. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242).

Topics: Aspirin; Heart; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor

Nearly 20% of patients on ticagrelor experience dyspnea, which may lead to treatment discontinuation in up to one-third of cases.. The authors sought to evaluate the incidence, predictors, and outcomes of dyspnea-related ticagrelor discontinuation after percutaneous coronary intervention (PCI).. In the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial, after 3 months of ticagrelor plus aspirin, patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. The occurrence of dyspnea associated with ticagrelor discontinuation was evaluated among all patients enrolled in the trial. A landmark analysis was performed at 3 months after PCI, that is, the time of randomization. Predictors of dyspnea-related ticagrelor discontinuation were obtained from multivariable Cox regression with stepwise selection of candidate variables.. The incidence of dyspnea-related ticagrelor discontinuation was 6.4% and 9.1% at 3 and 15 months after PCI, respectively. Independent predictors included Asian race (lower risk), smoking, prior PCI, hypercholesterolemia, prior coronary artery bypass, peripheral artery disease, obesity, and older age. Among 179 patients who discontinued ticagrelor because of dyspnea after randomization, ticagrelor monotherapy was not associated with a higher risk of subsequent ischemic events (composite of all-cause death, myocardial infarction, or stroke) compared with ticagrelor plus aspirin (5.0% vs 7.1%; P = 0.566).. In the TWILIGHT trial, dyspnea-related ticagrelor discontinuation occurred in almost 1 in 10 patients and tended to occur earlier rather than late after PCI. Several demographic and clinical conditions predicted its occurrence, and their assessment may help identify subjects at risk for therapy nonadherence.

Topics: Aspirin; Drug Therapy, Combination; Dyspnea; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19.. To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19.. An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021.. Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = 293) or a therapeutic dose of heparin only (usual care) (n = 269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor.. The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis.. Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P = .15).. Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization.. ClinicalTrials.gov Identifier: NCT04505774.

Topics: Aged; Aged, 80 and over; Anticoagulants; Clopidogrel; Comorbidity; COVID-19; COVID-19 Drug Treatment; Extracorporeal Membrane Oxygenation; Female; Hemorrhage; Heparin; Hospital Mortality; Humans; Inpatients; Male; Medical Futility; Middle Aged; Outcome Assessment, Health Care; Oxygen Inhalation Therapy; Platelet Activation; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Respiration, Artificial; Thrombosis; Ticagrelor; Time Factors; Treatment Outcome

To assess whether the efficacy and safety of ticagrelor vs. prasugrel in patients with acute coronary syndromes (ACSs) are influenced by pre-admission treatment with aspirin and/or clopidogrel.. Patients (n = 4018) were categorized into two groups: pre-admission aspirin and/or clopidogrel group (n = 1455) and no pre-admission aspirin or clopidogrel group (n = 2563). The primary endpoint was the composite of all-cause death, myocardial infarction, or stroke; the secondary safety endpoint was Bleeding Academic Research Consortium (BARC) type 3-5 bleeding, both at 1 year. Patients in the pre-admission aspirin and/or clopidogrel group had a higher risk of ischaemic events, but a similar risk of bleeding to patients in the no pre-admission aspirin or clopidogrel group (cumulative incidences 10.5% vs. 6.7%, and 5.7% vs. 5.7%, respectively). The primary endpoint occurred in 81/717 patients assigned to ticagrelor and 69/738 patients assigned to prasugrel in the pre-admission aspirin and/or clopidogrel group [11.5% vs. 9.5%; hazard ratio (HR) = 1.23; 95% confidence interval (CI) 0.89-1.69], and in 103/1295 patients assigned to ticagrelor and 68/1268 patients assigned to prasugrel in the no pre-admission aspirin or clopidogrel group [8.0% vs. 5.4%; HR = 1.50 (1.10-2.03); Pint = 0.38]. BARC type 3-5 bleeding events did not differ between ticagrelor and prasugrel in patients in the pre-admission aspirin and/or clopidogrel (6.2% vs. 4.5%) or no pre-admission aspirin or clopidogrel (5.3% vs. 5.1%) group (Pint = 0.54).. In patients with ACS, pre-admission therapy with aspirin and/or clopidogrel has no influence on the relative efficacy and safety of ticagrelor and prasugrel.

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor

The optimal antiplatelet strategy in the second year after percutaneous coronary intervention (PCI) remains unclear.. We aimed to compare ticagrelor monotherapy with aspirin monotherapy on clinical outcomes beyond 1 year post-PCI.. This post hoc subanalysis of the open-label, all-comers, randomised GLOBAL LEADERS trial, which compared 23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) with 12-month aspirin monotherapy following 12-month DAPT, only included patients who, at 12 months, were free from ischaemic and bleeding events and were adherent to their assigned antiplatelet therapy. The incidences of ischaemic events (all-cause death, any myocardial infarction, or any stroke) and bleeding events (Bleeding Academic Research Consortium [BARC] type 3 or 5 bleeding) during the second year (12-24 months) were compared between patients receiving either ticagrelor or aspirin monotherapy.. The present analysis included 11,121 (ticagrelor monotherapy n=5,308, and aspirin monotherapy n=5,813) of the 15,991 patients enrolled in GLOBAL LEADERS. During the second year, the ischaemic composite endpoint was lower with ticagrelor monotherapy compared to aspirin monotherapy (1.9% vs 2.6%: log-rank p=0.014, adjusted hazard ratio [HR] 0.74, 95% confidence interval [CI]: 0.58-0.96; p=0.022), which was primarily driven by a reduced risk of myocardial infarction. In contrast, BARC type 3 or 5 bleeding was numerically higher with ticagrelor monotherapy (0.5% vs 0.3%: log-rank p=0.051, adjusted HR 1.89, 95% CI: 1.03-3.45; p=0.005).. Patients free from events at the end of the first year post-PCI and who adhered to their prescribed regimen had a reduced risk of ischaemic events compared to aspirin monotherapy in the second year post-PCI.. gov: NCT01813435.

Topics: Aspirin; Drug Therapy, Combination; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

The risk/benefit tradeoff of dual antiplatelet therapy after percutaneous coronary intervention may vary in East Asian patients as compared with their non-East Asian counterparts.. The double-blind, placebo-controlled, randomized TWILIGHT trial (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) enrolled patients undergoing high-risk percutaneous coronary intervention. After 3 months of treatment with ticagrelor plus aspirin, event-free and adherent patients remained on ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding; the key secondary end point was the first occurrence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke.. Of 9006 enrolled and 7119 randomized patients in TWILIGHT, 1169 patients (13.0%) were enrolled at 27 Chinese sites in this prespecified substudy, of whom 1028 (14.4%) patients were randomized after 3 months. The incidence of the primary end point was 6.2% in the ticagrelor+aspirin group versus 3.5% in the ticagrelor+placebo group between randomization and 1 year (hazard ratio, 0.56 [95% CI, 0.31-0.99];. Ticagrelor monotherapy significantly reduced clinically relevant bleeding without increasing ischemic events as compared with ticagrelor plus aspirin in Chinese patients undergoing high-risk percutaneous coronary intervention.. URL: https://www.. gov; Unique identifier: NCT02270242.

Topics: Aspirin; Drug Therapy, Combination; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

We aimed to evaluate the treatment effects of ticagrelor monotherapy in the very high risk cohort of patients with concomitant diabetes mellitus (DM) and chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI).. In the TWILIGHT (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, after 3-month dual antiplatelet therapy with ticagrelor and aspirin post-PCI, event-free patients were randomized to either aspirin or placebo in addition to ticagrelor for 12 months. Those with available information on DM and CKD status were included in this subanalysis and were stratified by the presence or absence of either condition: 3391 (54.1%) had neither DM nor CKD (DM-/CKD-), 1822 (29.0%) had DM only (DM+/CKD-), 561 (8.9%) had CKD only (DM-/CKD+), and 8.0% had both DM and CKD (DM+/CKD+). The incidence of the primary endpoint of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding did not differ according to DM/CKD status (P-trend = 0.13), but there was a significant increase in BARC 3 or 5 bleeding (P-trend < 0.001) as well as the key secondary endpoint of death, myocardial infarction, or stroke (P-trend < 0.001). Ticagrelor plus placebo reduced bleeding events compared with ticagrelor plus aspirin across all four groups, including DM+/CKD+ patients with respect to BARC 2-5 [4.5% vs. 8.7%; hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.24-1.01] as well as BARC 3-5 (0.8% vs. 5.3%; HR 0.15, 95% CI 0.03-0.53) bleeding, with no evidence of heterogeneity. The risk of death, myocardial infarction, or stroke was similar between treatment arms across all groups.. Irrespective of the presence of DM, CKD, and their combination, ticagrelor monotherapy reduced the risk of bleeding without a significant increase in ischaemic events compared with ticagrelor plus aspirin.

Topics: Aspirin; Diabetes Mellitus; Drug Therapy, Combination; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Renal Insufficiency, Chronic; Stroke; Ticagrelor

Morphine is commonly used to relieve pain, anxiety and dyspnea in STEMI but it lowers blood pressure and delays the activity of oral antiplatelet agents. The impact of morphine on clinical outcomes remains unknown. This analysis was performed to determine if morphine use was associated with increased risk of adverse clinical events among STEMI patients treated with fibrinolytic therapy and clopidogrel or ticagrelor.. In the Ticagrelor in Patients with ST Elevation Myocardial Infarction Treated with Pharmacological Thrombolysis (TREAT) study, 3799 STEMI patients treated with fibrinolysis were randomized to receive clopidogrel or ticagrelor. Morphine use was left to the discretion of the treating physicians. In this pre-specified analysis, we evaluated clinical outcomes based on the use and timing of morphine administration. Outcomes were stratified by randomized treatment group. Multivariable analysis was performed using Inverse Probability Treatment Weighting (IPTW) weighting.. Morphine was used in 53% of patients. After adjustment using IPTW weighting, morphine use was associated with higher hazard of reinfarction at 7 days (HR 4.9, P = .0006) and 30 days (HR 1.7, P = .04), and lower hazard of major bleeding (HR 0.37, P = .006). There was no significant difference in mortality at any time point.. Among patients with STEMI treated with fibrinolytic therapy, morphine use was associated with a higher risk of early reinfarction and a lower risk of major bleeding but no difference in mortality.. clinicaltrials.gov Identifier: NCT02298088.

Topics: Clopidogrel; Hemorrhage; Humans; Morphine; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Thrombolytic Therapy; Ticagrelor; Treatment Outcome

The optimal P2Y. We identified 22,120 hospitalized ACS patients with HBR treated with aspirin combined with either clopidogrel (n = 17,420) or ticagrelor (n = 4700) in the Improving Care for Cardiovascular Disease in China-ACS (CCC-ACS) project between November 2014 and December 2019.. The median length of hospital stay was 10 days (interquartile range, 7-14 days). Compared with clopidogrel, ticagrelor was associated with a higher risk of in-hospital TIMI major or minor bleeding (4.8% vs 3.8%; adjusted OR 1.20; 95% CI 1.03-1.41; P = 0.022). The incidence of TIMI major bleeding (1.7% vs 1.1%, P = 0.005) and intracranial bleeding (0.8% vs 0.5%, P = 0.005) were also higher in the ticagrelor group than in the clopidogrel group. There was no significant difference in the rate of in-hospital major adverse cardiovascular and cerebrovascular event (MACCE) (a composite of all-cause death, myocardial infarction, stent thrombosis, or ischemic stroke) with ticagrelor compared with clopidogrel therapy (4.2% vs 4.3%; adjusted OR 1.08; 95% CI 0.90-1.28; P = 0.411). Outcomes in the propensity-matched cohorts and in sensitivity analyses were consistent with the those of the main analysis.. Among ACS patients with HBR, ticagrelor as compared with clopidogrel was associated with an increased risk of in-hospital major bleeding without a significant reduction in in-hospital MACCE.. https://www.. gov. Unique identifier: NCT02306616.

Topics: Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Hospitals; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Dual antiplatelet therapy (DAPT) with ticagrelor and aspirin has been found to be effective for secondary prevention after minor ischemic stroke or transient ischemic attack (TIA) in individuals who carry CYP2C19 loss-of-function (LOF) alleles; however, uncertainties remain about the time course of benefit and risk with ticagrelor and aspirin in these patients.. To obtain time-course estimates of efficacy and risk with ticagrelor and aspirin after minor stroke or TIA in individuals with CYP2C19 LOF alleles.. The Ticagrelor or Clopidogrel With Aspirin in High-risk Patients With Acute Nondisabling Cerebrovascular Events II (CHANCE-2) randomized clinical trial enrolled patients 40 years and older from 202 hospitals in China with acute minor stroke or TIA who carried CYP2C19 LOF alleles between September 23, 2019, and March 22, 2021, and were followed up for 90 days. All 6412 patients enrolled in the CHANCE-2 trial were included in this secondary analysis. Data were analyzed in October 2021.. Ticagrelor (180 mg on day 1 followed by 90 mg twice daily on days 2-90) or clopidogrel (300 mg on day 1 followed by 75 mg daily on days 2-90). All patients received aspirin (75-300 mg on day 1 followed by 75 mg daily for 21 days).. The efficacy outcome was major ischemic event, defined as the composite of ischemic stroke or nonhemorrhagic death. Safety outcomes included moderate to severe bleeding and any bleeding.. A total of 6412 patients were included (3205 in the ticagrelor and aspirin group and 3207 in the clopidogrel and aspirin group). The median (IQR) age was 65 (57-71) years, and 4242 patients (66%) were men. The reduction of major ischemic events with ticagrelor and aspirin predominately occurred in the first week (absolute risk reduction, 1.34%; 95% CI, 0.29 to 2.39) and attenuated but remained in the next 3 weeks (absolute risk reduction in the second week, 0.11%; 95% CI, -0.24 to 0.45; absolute risk reduction in the third week, 0.14%; 95% CI, -0.11 to 0.38; absolute risk reduction in the fourth week, 0.04%; 95% CI, -0.18 to 0.25). The risk of moderate to severe bleeding was consistently low in the ticagrelor and aspirin group. The absolute increase in any bleeding seen in the first week (0.87%; 95% CI, 0.25 to 1.50) remained in the next 3 weeks (absolute increase in the second week, 1.21%; 95% CI, 0.75 to 1.68; absolute increase in the third week, 0.33%; 95% CI, -0.05 to 0.72; absolute increase in the fourth week, 0.23%; 95% CI, -0.03 to 0.49).. Among patients with minor stroke or TIA who carried CYP2C19 LOF alleles, benefit with ticagrelor and aspirin was present predominately in the first week, with additional small benefit accruing in the next 2 weeks.

Topics: Aged; Alleles; Aspirin; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Therapy, Combination; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Ischemic Stroke; Male; Middle Aged; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

The phase 3 HESTIA3 study assessed the efficacy and safety of the reversible P2Y12 inhibitor ticagrelor vs placebo in preventing vaso-occlusive crises in pediatric patients with sickle cell disease (SCD). Patients aged 2 to 17 years were randomly assigned 1:1 to receive weight-based doses of ticagrelor or matching placebo. The primary end point was the rate of vaso-occlusive crises, a composite of painful crises and/or acute chest syndrome (ACS). Key secondary end points included number and duration of painful crises, number of ACS events, and number of vaso-occlusive crises requiring hospitalization or emergency department visits. Exploratory end points included the effect of ticagrelor on platelet activation. In total, 193 patients (ticagrelor, n = 101; placebo, n = 92) underwent randomization at 53 sites across 16 countries. The study was terminated 4 months before planned completion for lack of efficacy. Median ticagrelor exposure duration was 296.5 days. The primary end point was not met: estimated yearly incidence of vaso-occlusive crises was 2.74 in the ticagrelor group and 2.60 in the placebo group (rate ratio, 1.06; 95% confidence interval, 0.75-1.50; P = .7597). There was no evidence of efficacy for ticagrelor vs placebo across secondary end points. Median platelet inhibition with ticagrelor at 6 months was 34.9% predose and 55.7% at 2 hours' postdose. Nine patients (9%) in the ticagrelor group and eight patients (9%) in the placebo group had at least one bleeding event. In conclusion, no reduction of vaso-occlusive crises was seen with ticagrelor vs placebo in these pediatric patients with SCD. This trial was registered at www.clinicaltrials.gov as #NCT03615924.

Topics: Acute Chest Syndrome; Anemia, Sickle Cell; Child; Hemorrhage; Humans; Pain; Platelet Aggregation Inhibitors; Ticagrelor

To estimate the incidence and HRs for bleeding for different dual antiplatelet therapies (DAPT) in a real-world population with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in England.. A retrospective, population-based cohort study emulating a target randomised controlled trial (tRCT).. Linked Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES).. Primary and secondary care.. Patients ≥18 years old with ACS undergoing emergency PCI.. Aspirin and clopidogrel (AC, reference) versus aspirin and prasugrel (AP) or aspirin and ticagrelor (AT); AP evaluated only in patients with ST-elevation myocardial infarction (STEMI).. Primary: any bleeding up to 12 months after the index event (HES- or CPRD- recorded). Secondary: HES-recorded bleeding, CPRD-recorded bleeding, all-cause and cardiovascular mortality, mortality from bleeding, myocardial infarction, stroke, additional coronary intervention and major adverse cardiovascular and cerebrovascular events (MACCE).. In ACS, the rates of any bleeding for AC and AT were 89 per 1000 person years and 134 per 1000 person years, respectively. In STEMI, rates for AC, AP and AT were 93 per 1000 person years, 138 per 1000 person years and 143 per 100 person years, respectively. In ACS, compared with AC, AT increased the hazard of any bleeding (HR: 1.47, 95% CI 1.19 to 1.82) but did not reduce MACCE (HR: 1.06, 95% CI 0.89 to 1.27). In STEMI, compared with AC, AP and AT increased the hazard of any bleeding (HR: 1.77, 95% CI 1.21 to 2.59 and HR: 1.50, 95% CI 1.10 to 2.05, respectively) but did not reduce MACCE (HR: 1.10, 95% CI 0.80 to 1.51 and HR: 1.21, 95% CI 0.94 to 1.51, respectively). Non-adherence to the prescribed DAPT regimen was 28% in AC (29% in STEMI only), 31% in AP (STEMI only) and 33% in AT (32% in STEMI only).. In a real-world population with ACS, DAPT with ticagrelor or prasugrel are associated with increased bleeding compared with DAPT with clopidogrel.. ISRCTN76607611.

Topics: Acute Coronary Syndrome; Adolescent; Aspirin; Clopidogrel; Cohort Studies; Dinucleoside Phosphates; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Retrospective Studies; ST Elevation Myocardial Infarction; Ticagrelor

Prior coronary artery bypass graft surgery (CABG) patients undergoing percutaneous coronary intervention (PCI) are often older and present with multiple comorbidities. Ticagrelor monotherapy after a short course of dual antiplatelet therapy (DAPT) has emerged as an effective bleeding-avoidance strategy among high-risk patients.. We aimed to examine the effects of ticagrelor with or without aspirin in prior CABG patients undergoing PCI within the TWILIGHT trial.. After 3 months of ticagrelor plus aspirin, patients were randomised to either aspirin or placebo, in addition to ticagrelor, for 12 months and compared by prior CABG status. The primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding. The key secondary endpoint was all-cause death, myocardial infarction (MI), or stroke.. Out of 7,119 patients, a total of 703 (10.8%) patients had prior CABG within the randomised cohort. Prior CABG patients had more comorbidities and a higher incidence of BARC type 2, 3, or 5 bleeding and death, MI or stroke at 1 year after randomisation, compared with patients without prior CABG. Ticagrelor monotherapy was associated with significantly less BARC 2, 3, or 5 bleeding among prior CABG patients compared with DAPT (4.9% vs 9.6%, hazard ratio [HR] 0.50, 95% confidence interval [CI]: 0.28 to 0.90; p. In high-risk patients with prior CABG, ticagrelor monotherapy reduced bleeding without compromising ischaemic outcomes compared with ticagrelor plus aspirin.

Topics: Aspirin; Coronary Artery Bypass; Drug Therapy, Combination; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

Oral activated factor XI (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without substantially increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI).. We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6 to 12 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo.. The median age was 68 years, 23% of participants were women, 51% had ST-segment-elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity, with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian versus placebo: hazard ratio, 0.98 [90% CI, 0.71-1.35]). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian 20 and 50 mg versus placebo: hazard ratio, 1.05 [90% CI, 0.69-1.61]).. In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI.. URL: https://www.. gov; Unique identifier: NCT04304534; URL: https://www.clinicaltrialsregister.eu/ctr-search/search; Unique identifier: 2019-003244-79.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Aspirin; Double-Blind Method; Factor XIa; Female; Hemorrhage; Humans; Male; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor; Treatment Outcome

The relative efficacy and safety of more potent P2Y. This post hoc analysis of the ISAR-REACT 5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5) included patients with acute coronary syndrome undergoing percutaneous coronary intervention, randomized to ticagrelor or prasugrel, in whom HBR was defined as per Academic Research Consortium criteria. The primary (efficacy) end point was the composite of all-cause death, myocardial infarction, or stroke. The secondary (safety) end point was Bleeding Academic Research Consortium type 3 to 5 bleeding. Outcomes were assessed 12 months after randomization.. Out of the 3239 patients included in this analysis, 486 fulfilled the criteria for Academic Research Consortium-HBR definition (HBR group; ticagrelor, n=230 and prasugrel, n=256), while 2753 did not (non-HBR group; ticagrelor, n=1375 and prasugrel, n=1378). Compared with the non-HBR group, the HBR group had a higher risk for the primary (hazard ratio [HR]=3.57 [95% CI, 2.79-4.57];. In patients with acute coronary syndrome undergoing percutaneous coronary intervention, HBR status increased both ischemic and bleeding risk without significant impact on the relative efficacy and safety of either ticagrelor or prasugrel. These results warrant confirmation in larger cohorts.. URL: https://www.. gov; Unique identifier: NCT01944800.

Topics: Acute Coronary Syndrome; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Assessment; Ticagrelor; Treatment Outcome

Data regarding prognosis and management after nuisance bleeding (NB) is limited. The purpose was to examine the prognostic significance of NB in patients receiving potent dual antiplatelet treatment (DAPT) after acute myocardial infarction and the impact of de-escalation of DAPT on clinical outcomes thereafter.. From the TALOS-AMI trial (Ticagrelor Versus Clopidogrel in Stabilized Patients With Acute Myocardial Infarction)' 2583 patients were used to investigate the clinical impact of NB (defined as Bleeding Academic Research Consortium [BARC] 1 bleeding) during 1-month treatment with ticagrelor-based DAPT after acute myocardial infarction. We assessed the associations between NB within 1 month and BARC 2, 3, or 5 bleeding and major adverse cardiovascular event (a composite of cardiovascular death, myocardial infarction, stroke) from 1 to 12 months. We also evaluated the effect of de-escalation to clopidogrel in patients with or without NB.. NB occurred in 416 patients (16.7%) after 1 month of ticagrelor-based DAPT. At 1 year, NB was not associated with increase in BARC 2, 3, or 5 bleeding (hazard ratio [HR]' 1.29 [95% CI' 0.7-2.14]) and major adverse cardiovascular event (HR' 1.72 [95% CI' 0.87-3.39]). However, patients with NB had an increased risk of BARC 2, 3, or 5 bleeding at 6 months (HR, 1.94 [95% CI, 1.08-3.48];. NB was frequent in patients with acute myocardial infarction on 1-month ticagrelor-based DAPT and was associated with an early increase of bleeding. DAPT de-escalation after NB may reduce bleeding without increasing ischemic events.. URL: https://www.. gov; Unique identifier: NCT02018055.

Topics: Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prognosis; Ticagrelor; Treatment Outcome

The evidence for the comparative effectiveness and safety of ticagrelor versus clopidogrel in older patients with acute coronary syndrome (ACS) is limited, especially in the acute phase of ACS. This study aimed to compare the in-hospital outcomes of ticagrelor versus clopidogrel in older patients with ACS.. Hospitalised ACS patients aged ≥75 years who were recruited to the Improving Care for Cardiovascular Disease in China-ACS project between November 2014 and December 2019 and received aspirin and P2Y12 receptor inhibitors within 24 h after first medical contact were included. The primary outcomes were in-hospital major adverse cardiovascular events (MACE) and major bleeding. Multivariable Cox regression was performed to evaluate the comparative effectiveness and safety of ticagrelor and clopidogrel. Inverse probability of treatment weighting (IPTW) and propensity score matching analyses were performed to evaluate the robustness of the results.. Of 18,244 ACS patients, 18.5% received ticagrelor. Multivariable-adjusted analysis revealed comparable risks of in-hospital MACE between patients receiving ticagrelor and clopidogrel (hazard ratio [HR] 1.12, 95% confidence interval [CI] 0.92-1.35). However, ticagrelor use was associated with 45% higher risk of in-hospital major bleeding compared with clopidogrel use (HR 1.45, 95% CI 1.09-1.91). Similar results were found in the IPTW analysis.. ACS patients aged ≥75 years receiving ticagrelor during the acute phase had similar risk of in-hospital MACE, but higher risk of in-hospital major bleeding compared with those receiving clopidogrel. More evidence is needed to guide the use of P2Y12 receptor inhibitors during hospitalisation in older patients with ACS.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02306616.

Topics: Acute Coronary Syndrome; Aged; Cardiovascular Diseases; China; Clopidogrel; Hemorrhage; Hospitals; Humans; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Quality Improvement; Ticagrelor

Topics: Acute Coronary Syndrome; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor; Treatment Outcome

Sex-specific analyses of direct head-to-head comparisons between newer P2Y. This pre-specified analysis of the ISAR-REACT 5 trial included 956 women and 3,062 men with ACS randomly assigned to either ticagrelor or prasugrel. The primary endpoint was the 12-month incidence of death, myocardial infarction, or stroke; the safety endpoint was the 12-month incidence of bleeding (type 3-5 according to the Bleeding Academic Research Consortium [BARC]).. Although there was no significant interaction between sex and treatment effect of study drugs, the superior efficacy of prasugrel was more evident among men. No difference in bleeding between the two study groups was seen for both women and men.

Topics: Acute Coronary Syndrome; Female; Hemorrhage; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor; Treatment Outcome

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Coronary Artery Disease; Drug-Eluting Stents; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Ticagrelor

In patients with acute myocardial infarction receiving potent antiplatelet therapy, the bleeding risk remains high during the maintenance phase. We sought data on a uniform unguided de-escalation strategy of dual antiplatelet therapy (DAPT) from ticagrelor to clopidogrel after acute myocardial infarction.. In this open-label, assessor-masked, multicentre, non-inferiority, randomised trial (TALOS-AMI), patients at 32 institutes in South Korea with acute myocardial infarction receiving aspirin and ticagrelor without major ischaemic or bleeding events during the first month after index percutaneous coronary intervention (PCI) were randomly assigned in a 1:1 ratio to a de-escalation (clopidogrel plus aspirin) or active control (ticagrelor plus aspirin) group. Unguided de-escalation without a loading dose of clopidogrel was adopted when switching from ticagrelor to clopidogrel. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or bleeding type 2, 3, or 5 according to Bleeding Academic Research Consortium (BARC) criteria from 1 to 12 months. A non-inferiority test was done to assess the safety and efficacy of de-escalation DAPT compared with standard treatment. The hazard ratio (HR) for de-escalation versus active control group in a stratified Cox proportional hazards model was assessed for non-inferiority by means of an HR margin of 1·34, which equates to an absolute difference of 3·0% in the intention-to-treat population and, if significant, a superiority test was done subsequently. To ensure statistical robustness, additional analyses were also done in the per-protocol population. This trial is registered at ClinicalTrials.gov, NCT02018055.. In stabilised patients with acute myocardial infarction after index PCI, a uniform unguided de-escalation strategy significantly reduced the risk of net clinical events up to 12 months, mainly by reducing the bleeding events.. ChongKunDang Pharm, Medtronic, Abbott, and Boston Scientific.

Topics: Aged; Aspirin; Clopidogrel; Dual Anti-Platelet Therapy; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Republic of Korea; Stroke; Ticagrelor; Treatment Outcome

Patients at high bleeding risk (HBR) represent a prevalent subgroup among those undergoing percutaneous coronary intervention (PCI). Early aspirin discontinuation after a short course of dual antiplatelet therapy (DAPT) has emerged as a bleeding avoidance strategy. The aim of this study was to assess the effects of ticagrelor monotherapy after 3-month DAPT in a contemporary HBR population.. This prespecified analysis of the TWILIGHT trial evaluated the treatment effects of early aspirin withdrawal followed by ticagrelor monotherapy in HBR patients undergoing PCI with drug-eluting stents. After 3 months of ticagrelor plus aspirin, event-free patients were randomized to 12 months of aspirin or placebo in addition to ticagrelor. A total of 1064 (17.2%) met the Academic Research Consortium definition for HBR. Ticagrelor monotherapy reduced the incidence of the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding compared with ticagrelor plus aspirin in HBR (6.3% vs. 11.4%; hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.35-0.82) and non-HBR patients (3.5% vs. 5.9%; HR 0.59, 95% CI 0.46-0.77) with similar relative (Pinteraction = 0.67) but a trend towards greater absolute risk reduction in the former [-5.1% vs. -2.3%; difference in absolute risk differences (ARDs) -2.8%, 95% CI -6.4% to 0.8%, P = 0.130]. A similar pattern was observed for more severe BARC 3 or 5 bleeding with a larger absolute risk reduction in HBR patients (-3.5% vs. -0.5%; difference in ARDs -3.0%, 95% CI -5.2% to -0.8%, P = 0.008). There was no significant difference in the key secondary endpoint of death, myocardial infarction, or stroke between treatment arms, irrespective of HBR status.. Among HBR patients undergoing PCI who completed 3-month DAPT without experiencing major adverse events, aspirin discontinuation followed by ticagrelor monotherapy significantly reduced bleeding without increasing ischaemic events, compared with ticagrelor plus aspirin. The absolute risk reduction in major bleeding was larger in HBR than non-HBR patients.

Topics: Drug Therapy, Combination; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Background We aimed to evaluate the age-dependent effect of ticagrelor monotherapy after 3-month dual-antiplatelet therapy (DAPT) versus ticagrelor-based 12-month DAPT on major bleeding and cardiovascular events in patients with acute coronary syndrome. Methods and Results From the TICO trial (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus-eluting Stent for Acute Coronary Syndrome), which randomized 3056 patients (median age, 61 years) to the ticagrelor monotherapy after 3-month DAPT group or ticagrelor-based 12-month DAPT group, this post hoc analysis evaluated the age-dependent effect of the treatment strategies on the primary end point (a composite of major bleeding, death, myocardial infarction, stent thrombosis, stroke, or target-vessel revascularization) using the subpopulation treatment effect pattern plot. The cutoff age for distinguishing patients with greater benefit from this strategy was also determined. The risk reduction effect of ticagrelor monotherapy after 3-month DAPT versus ticagrelor-based 12-month DAPT on the primary end point gradually increased with age and was more marked from the subpopulation of age 64 years with the change point. With this cutoff value of 64 years, the occurrence of the primary end point was significantly lower in the ticagrelor monotherapy after 3-month DAPT group than in the ticagrelor-based 12-month DAPT group (4.4% versus 9.0%;

Topics: Acute Coronary Syndrome; Age Distribution; Aged; Aspirin; Cardiovascular Diseases; Drug Therapy, Combination; Hemorrhage; Humans; Middle Aged; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Patients undergoing staged percutaneous coronary intervention (SPCI) are exposed to extended duration of antiplatelet therapy, and a novel aspirin-free antiplatelet regimen after SPCI should be specifically evaluated among these patients. This is a prespecified substudy of the GLOBAL LEADERS which is a randomized, open-label trial, comparing an experimental regimen of 1-month dual antiplatelet therapy (DAPT; ticagrelor and aspirin) followed by 23-month ticagrelor monotherapy to a reference regimen of 12-month DAPT followed by 12-month aspirin monotherapy. Patients were stratified according to whether or not SPCI was performed. The impact of the timing of SPCI on clinical outcomes was also investigated. Of 15,968 randomized patients, 1,651 patients underwent SPCI within 3 months. These patients with SPCI had a significantly higher risk of bleeding and ischemic endpoints than those without SPCI. In patients undergoing SPCI, the primary endpoint (composite of all-cause death or new Q-wave myocardial infarction at 2 years) and secondary safety endpoint (Bleeding Academic Research Consortium [BARC]-defined bleeding 3 or 5) were similar in the 2 regimens. However, in patients presenting with acute coronary syndrome (ACS), the experimental regimen reduced a risk of BARC 3 or 5 bleeding (1.8% vs 4.5%; HR 0.387; 95% CI 0.179 to 0.836; p = 0.016). In patients undergoing SPCI later than 10 days after index procedure, this risk reduction was still prominent (0.8% vs 2.3%; HR 0.321; 95% CI 0.116 to 0.891; p = 0.029). In conclusion, patients undergoing SPCI are at high risk and may need special attention from clinicians. In ACS patients undergoing SPCI, a novel aspirin-free antiplatelet regimen appears to be associated with a lower bleeding risk than with standard DAPT.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Coronary Stenosis; Drug-Eluting Stents; Dual Anti-Platelet Therapy; Female; Hemorrhage; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Topics: Aged; Aspirin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Europe; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Platelet Aggregation Inhibitors; Prognosis; Survival Rate; Thrombolytic Therapy; Ticagrelor; Time Factors

The aim of this pooled sub-analysis of the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) and Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial was to compare the clinical outcome of patients with acute myocardial infarction complicated by cardiogenic shock treated either with clopidogrel or the newer, more potent ADP-receptor antagonists prasugrel or ticagrelor.. This pooled sub-analysis is the largest analysis on safety and efficacy of three oral ADP-receptor antagonists and shows that acute therapy with either clopidogrel, prasugrel or ticagrelor is no independent predictor of 1-year mortality. Treatment with ticagrelor seems independently associated with less in-hospital moderate and severe bleeding events compared to clopidogrel. This finding might be due to selection bias and should be interpreted with caution.

Topics: Aged; Aged, 80 and over; Clopidogrel; Female; Follow-Up Studies; Hemorrhage; Humans; Intra-Aortic Balloon Pumping; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Shock, Cardiogenic; Ticagrelor

Controversy remains regarding the optimal antiplatelet regimen in patients with acute coronary syndrome (ACS). This study sought to investigate the efficacy and safety of P2Y12 inhibitor monotherapy compared with conventional dual antiplatelet therapy (DAPT) and aspirin monotherapy in patients with ACS undergoing percutaneous coronary intervention. Data on 4,453 patients were pooled from SMART-DATE and SMART-CHOICE randomized trials. Antiplatelet therapy regimens were categorized as P2Y12 inhibitor monotherapy (P2Y12 inhibitor monotherapy after 3-month DAPT), conventional DAPT (12-month or longer DAPT), and aspirin monotherapy (aspirin monotherapy after 6-month DAPT). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE, a composite of all-cause death, myocardial infarction, and stroke). Inverse-probability of treatment-weighted (IPTW) analysis was performed. At 1 year, patients in the P2Y12 inhibitor monotherapy had a comparable risk of MACCE compared with those in the conventional DAPT (IPTW-adjusted hazard ratio [HR], 0.655; 95% confidence interval [CI] 0.393 to 1.094; p = 0.106), and tended to have a lower risk of MACCE than those in the aspirin monotherapy (IPTW-adjusted HR, 0.606; 95% CI, 0.347 to 1.058; p = 0.078). The adjusted hazard for the Bleeding Academic Research Consortium (BARC) type 2 to 5 bleeding was significantly lower in P2Y12 inhibitor monotherapy than in conventional DAPT (IPTW-adjusted HR, 0.341; 95% CI, 0.190 to 0.614; p < 0.001) and in aspirin monotherapy (IPTW-adjusted HR, 0.359; 95% CI, 0.182 to 0.708; p = 0.003). In conclusion, among patients with ACS undergoing PCI, P2Y12 inhibitor monotherapy after 3-month DAPT reduced risk of bleeding compared with conventional DAPT and aspirin monotherapy after 6-month DAPT without increasing MACCE.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Clopidogrel; Drug-Eluting Stents; Dual Anti-Platelet Therapy; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor

Background Coronary stent type and risk of stent thrombosis remain important factors affecting recommended duration of dual antiplatelet therapy. We investigated the efficacy and safety of long-term ticagrelor in patients with prior coronary stenting enrolled in the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) trial. Methods and Results Patients in PEGASUS-TIMI 54 had a myocardial infarction 1 to 3 year prior and were randomized 1:1:1 to ticagrelor 60 or 90 mg BID or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular events). Stent thrombosis was prospectively adjudicated (Academic Research Consortium definition). Baseline characteristics were compared by most recent stent type (bare metal versus drug-eluting stent and first- versus later-generation drug-eluting stent). Treatment arms were compared using Cox proportional hazards models. Of 21 162 patients randomized, 80% (n=16 891) had prior coronary stenting. Following randomization, myocardial infarction was the most frequent ischemic event in patients with prior stenting in the placebo arm, occurring in 5.2% of patients (Type 1: 4.1%), followed by cardiovascular death (2.3%), stroke (1.7%), and stent thrombosis (0.9%). Ticagrelor

Topics: Drug Therapy, Combination; Drug-Eluting Stents; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Secondary Prevention; Stents; Stroke; Thrombosis; Ticagrelor; Treatment Outcome

Women experience worse ischemic and bleeding outcomes after percutaneous coronary intervention (PCI).. To assess the association of sex with patient outcomes at 2 years after contemporary PCI and with the efficacy and safety of 2 antiplatelet strategies.. This study is a prespecified subgroup analysis of the investigator-initiated, prospective, randomized GLOBAL LEADERS study evaluating 2 strategies of antiplatelet therapy after PCI in an unselected population including 130 secondary/tertiary care hospitals in different countries. The main study enrolled 15 991 unselected patients undergoing PCI between July 2013 and November 2015. Patients had an outpatient clinic visit at 30 days and 3, 6, 12, 18, and 24 months after the index procedure. Data were analyzed between January 1, 2019, and March 31, 2019.. Eligible patients were randomized to either the experimental or reference antiplatelet strategy. Experimental strategy consisted of 1 month of dual antiplatelet therapy (DAPT) followed by 23 months of ticagrelor monotherapy, while the reference strategy comprised of 12 months of DAPT followed by 12 months of aspirin monotherapy.. The primary efficacy end point was the composite of all-cause mortality and new Q-wave myocardial infarction at 2 years. The secondary safety end point was Bleeding Academic Research Consortium type 3 or 5 bleeding.. Of the 15 968 patients included in this study, 3714 (23.3%) were women. The risk of the primary end point at 2 years was similar between women and men (adjusted hazard ratio [HR], 1.00; 95% CI, 0.83-1.20). Compared with men, women had higher risk of Bleeding Academic Research Consortium type 3 or 5 bleeding (adjusted HR, 1.32; 95% CI, 1.04-1.67) and hemorrhagic stroke at 2 years (adjusted HR, 4.76; 95% CI, 1.92-11.81). At 2 years, there was no between-sex difference in the efficacy and safety of the 2 antiplatelet strategies. At 1 year, compared with DAPT, ticagrelor monotherapy was associated with a lower risk of bleeding in men (HR, 0.72; 95% CI, 0.53-0.98) but not in women (HR, 1.23; 95% CI, 0.80-1.89; P for interaction = .045).. Compared with men, women experienced a higher risk of bleeding and hemorrhagic stroke after PCI. The effect of 2 antiplatelet strategies on death and Q-wave myocardial infarction following PCI did not differ between the sexes at 2 years.. ClinicalTrials.gov identifier: NCT01813435.

Topics: Aged; Aspirin; Coronary Artery Disease; Drug-Eluting Stents; Dual Anti-Platelet Therapy; Female; Hemorrhage; Hemorrhagic Stroke; Humans; Ischemic Stroke; Male; Middle Aged; Mortality; Myocardial Infarction; Myocardial Revascularization; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Secondary Prevention; Sex Factors; Thrombosis; Ticagrelor

 Glycoprotein IIb/IIIa inhibitors (GPIs) in combination with clopidogrel improve clinical outcome in ST-elevation myocardial infarction (STEMI); however, finding a balance that minimizes both thrombotic and bleeding risk remains fundamental. The efficacy and safety of GPI in addition to ticagrelor, a more potent P2Y12-inhibitor, have not been fully investigated..  1,630 STEMI patients who underwent primary percutaneous coronary intervention (PCI) were analyzed in this subanalysis of the ATLANTIC trial. Patients were divided in three groups: no GPI, GPI administration routinely before primary PCI, and GPI administration in bailout situations. The primary efficacy outcome was a composite of death, myocardial infarction, urgent target revascularization, and definite stent thrombosis at 30 days. The safety outcome was non-coronary artery bypass graft (CABG)-related PLATO major bleeding at 30 days..  Use of GPIs in addition to ticagrelor in STEMI patients was not associated with an improvement in 30-day ischemic outcome. A significant increase in 30-day non-CABG-related PLATO major bleeding was seen in patients who received GPIs in a bailout situation.

Topics: Aged; Clopidogrel; Double-Blind Method; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; ST Elevation Myocardial Infarction; Survival Analysis; Thrombosis; Ticagrelor; Treatment Outcome

Rates and predictors of major bleeding in patients with peripheral artery disease (PAD) treated with antiplatelets have not been well studied. This post hoc analysis of EUCLID aimed to determine the incidence of major/minor bleeding, predictors of major bleeding, and risk of major adverse cardiovascular events (MACE) following major bleeding events.. EUCLID, a multicenter randomized controlled trial of 13,885 patients with symptomatic PAD, compared ticagrelor with clopidogrel for the prevention of MACE. The primary safety end point was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. Baseline characteristics were used to develop a multivariable model to determine factors associated with TIMI major bleeding. The occurrence and timing of MACE relative to a first major bleeding event were determined.. TIMI major bleeding occurred in 2.3% of participants overall (0.94 event/100 patient-years). There was no significant difference in major bleeding rates by treatment assignment. Factors associated with TIMI major bleeding included older age, geographic region, Rutherford class, and β-blocker use. Patients with TIMI major bleeding postrandomization had an increased risk of MACE (hazard ratio [HR] 4.46; 95% CI 3.40-5.84; P < .0001) compared with those without major bleeding; the association was strongest within 30 days after a bleeding event.. In patients with symptomatic PAD, 0.94 major bleeding event/100 patient-years was observed and associated with older age, residing in North America, disease severity, and β-blocker use. Patients who had a major bleeding event were significantly more likely to experience MACE, especially within the first 30 days, when compared with patients who did not have major bleeding.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Cardiovascular Diseases; Clopidogrel; Double-Blind Method; Female; Hemorrhage; Humans; Incidence; Intention to Treat Analysis; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Residence Characteristics; Risk Factors; Ticagrelor; Time Factors

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor has become the standard of care to reduce thrombotic events in patients with acute coronary syndrome or after percutaneous coronary intervention (PCI). The role of routine platelet function testing (PFT) in patients treated with DAPT after PCI remains controversial and evidence of PFT-guided antiplatelet therapy for patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI is limited.. We analyzed 1,353 consecutive STEMI patients undergoing primary PCI. PFT was performed 72 hr postprocedure using a vasodilator-stimulated phosphoprotein assay. The primary endpoint of major adverse cardio-cerebral events (MACCEs) was defined as a composite of all-cause death, cardiac death, nonfatal myocardial infarction, target vessel revascularization, and ischemic stroke. Patients with high platelet reactivity (HPR) were randomized to receive an intensified antiplatelet strategy by switching from clopidogrel to ticagrelor (HPR switch group) or to continue on clopidogrel (HPR nonswitch group). One-year clinical outcomes were compared among the groups.. The baseline clinical characteristics were comparable across all groups (all p > .05). At the 1-year clinical follow-up, the primary endpoint of MACCE was significantly higher in the HPR nonswitch group than in the non-HPR and HPR switch groups (19.49% vs. 10.20% or 8.57%, p < .05), which was mainly caused by higher mortality (14.87% vs. 4.51% or 5.71%, p < .05). Major bleeding events were comparable across the groups.. In STEMI patients with HPR, identified by vasodilator stimulated phosphoprotein (VASP)-determined PFT, switching clopidogrel to ticagrelor could significantly improve 1-year clinical outcomes without increasing the risk of bleeding.

Topics: Aged; Aspirin; Biomarkers; Blood Platelets; Cell Adhesion Molecules; China; Clopidogrel; Drug Substitution; Dual Anti-Platelet Therapy; Female; Hemorrhage; Humans; Male; Microfilament Proteins; Middle Aged; Percutaneous Coronary Intervention; Phosphoproteins; Platelet Aggregation Inhibitors; Platelet Function Tests; Predictive Value of Tests; Prospective Studies; Recurrence; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Treatment Outcome

This study assessed the ability of the dual-antiplatelet therapy (DAPT) score in stratifying ischemic and bleeding risk in a contemporary percutaneous coronary intervention (PCI) population.. The DAPT score is recommended by guidelines as a tool to stratify ischemic and bleeding risk. Its utility in contemporary PCI is unknown.. The study studied patients in GLOBAL LEADERS (A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation) who were free of major ischemic and bleeding events and adhered to antiplatelet strategy during the first year after PCI. The primary ischemic endpoint was the composite of myocardial infarction or stent thrombosis. The primary bleeding endpoint was Bleeding Academic Research Consortium type 3 or 5. Outcomes from 12 to 24 months after PCI were compared according to the DAPT score.. Of 11,289 patients that were event-free after the first year, 6,882 and 4,407 patients had low (<2) and high (≥2) DAPT scores, respectively. Compared with a low DAPT score, patients with a high DAPT score had a higher rate of the composites of myocardial infarction or stent thrombosis (0.70% vs. 1.55%; p < 0.0001). The rate of Bleeding Academic Research Consortium type 3 or 5 bleeding was 0.54% and 0.30% in the low and high DAPT score groups, respectively (p = 0.058). The effect of ticagrelor versus aspirin monotherapy on primary ischemic and bleeding endpoints during the second year were no different among the 2 groups.. The DAPT score can stratify ischemic but not bleeding risk in a contemporary PCI population during the second year. The score did not provide additional value for selection of antiplatelet strategy beyond the first year.

Topics: Acute Coronary Syndrome; Aged; Clinical Decision Rules; Clinical Decision-Making; Coronary Artery Disease; Coronary Thrombosis; Drug Administration Schedule; Dual Anti-Platelet Therapy; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Progression-Free Survival; Prospective Studies; Risk Assessment; Risk Factors; Stents; Ticagrelor; Time Factors

We evaluated the association of pulse pressure (PP) and different antiplatelet regimes with clinical and safety outcomes in an all-comers percutaneous coronary intervention (PCI) population.. In this analysis of GLOBAL LEADERS (n = 15,936) we compared the experimental therapy of 23 months of ticagrelor after 1 month of dual-antiplatelet therapy (DAPT) vs standard DAPT for 12 months followed by aspirin monotherapy in subjects who underwent PCI and were divided into 2 groups according to the median PP (60 mm Hg). The primary end point (all-cause death or new Q-wave myocardial infarction) and the composite end points: patient-oriented composite end points (POCE), Bleeding Academic Research Consortium (BARC) 3 or 5, and net adverse clinical events (NACE) were evaluated.. At 2 years, subjects in the high-PP group (n = 7971) had similar rates of the primary end point (4.3% vs 3.9%; P = 0.058), POCE (14.9% vs 12.7%; P = 0.051), and BARC 3 or 5 (2.5% vs 1.7%; P = 0.355) and higher rates of NACE (16.4% vs 13.7%; P = 0.037) compared with the low-PP group (n = 7965). Among patients with PP < 60 mm Hg, the primary end point (3.4% vs 4.4%, adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.61-0.96), POCE (11.8% vs 13.5%, aHR 0.86, 95% CI 0.76-0.98), NACE (12.8% vs 14.7%, aHR 0.85, 95% CI 0.76-0.96), and BARC 3 or 5 (1.4% vs 2.1%, aHR 0.69, 95% CI 0.49-0.97) were lower with ticagrelor monotherapy compared with DAPT. The only significant interaction was for BARC 3 or 5 (P = 0.008).. After contemporary PCI, subjects with high PP levels experienced high rates of NACE at 2 years. In those with low PP, ticagrelor monotherapy led to a lower risk of bleeding events compared with standard DAPT.

Topics: Aged; Blood Pressure; Dual Anti-Platelet Therapy; Female; Hemorrhage; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor

P2Y. The purpose of this study was to examine the effect of ticagrelor monotherapy versus ticagrelor plus aspirin among patients with DM undergoing PCI.. This was a pre-specified analysis of the DM cohort in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial. After 3 months of ticagrelor plus aspirin, patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. The primary endpoint was Bleeding Academic Research Consortium 2, 3, or 5 bleeding. The composite ischemic endpoint was all-cause death, myocardial infarction, or stroke.. Patients with DM comprised 37% (n = 2,620) of the randomized cohort and were characterized by more frequent comorbidities and a higher prevalence of multivessel disease. The incidence of Bleeding Academic Research Consortium 2, 3, or 5 bleeding was 4.5% and 6.7% among patients with DM randomized to ticagrelor plus placebo versus ticagrelor plus aspirin (hazard ratio: 0.65; 95% confidence interval: 0.47 to 0.91; p = 0.012). Ticagrelor monotherapy was not associated with an increase in ischemic events compared with ticagrelor plus aspirin (4.6% vs. 5.9%; hazard ratio: 0.77; 95% confidence interval: 0.55 to 1.09; p = 0.14). In the overall trial population, there was no significant interaction between DM status and treatment group for the primary bleeding or ischemic endpoints.. Compared with ticagrelor plus aspirin, the effect of ticagrelor monotherapy in reducing the risk of clinically relevant bleeding without any increase in ischemic events was consistent among patients with or without DM undergoing PCI. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242).

Topics: Aspirin; Diabetes Mellitus; Double-Blind Method; Drug Therapy, Combination; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Prospective Studies; Purinergic P2Y Receptor Antagonists; Risk Factors; Ticagrelor

Whether a regimen of ticagrelor monotherapy attenuates bleeding complications without increasing ischemic risk in patients undergoing complex percutaneous coronary intervention (PCI) is unknown.. The purpose of this study was to evaluate the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients undergoing complex PCI from the randomized, double-blind, placebo-controlled TWILIGHT (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial.. In the TWILIGHT trial, after 3 months of ticagrelor plus aspirin, event-free and adherent patients remained on ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. Complex PCI was defined as any of the following: 3 vessels treated, ≥3 lesions treated, total stent length >60 mm, bifurcation with 2 stents implanted, atherectomy device use, left main PCI, surgical bypass graft or chronic total occlusion as target lesions. Bleeding and ischemic endpoints were evaluated at 1 year after randomization.. Among 7,119 patients randomized in the main trial, complex PCI was performed in 2,342 patients. Compared to ticagrelor plus aspirin, ticagrelor plus placebo resulted in significantly lower rates of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding (4.2% vs. 7.7%; hazard ratio [HR]: 0.54; 95% confidence interval [CI]: 0.38 to 0.76). BARC type 3 or 5 bleeding was also significantly reduced (1.1% vs. 2.6%; HR: 0.41; 95% CI: 0.21 to 0.80). There were no significant between-group differences in death, myocardial infarction, or stroke (3.8% vs. 4.9%; HR: 0.77; 95% CI: 0.52 to 1.15), nor in stent thrombosis.. Among patients undergoing complex PCI who initially completed 3 months of ticagrelor plus aspirin, continuation of ticagrelor monotherapy was associated with lower incidence of bleeding without increasing the risk of ischemic events compared to continuing ticagrelor plus aspirin. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242).

Topics: Aged; Aspirin; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Purinergic P2Y Receptor Antagonists; Ticagrelor

The REDUAL PCI trial (Evaluation of Dual Therapy With Dabigatran vs Triple Therapy With Warfarin in Patients With AF That Undergo a PCI With Stenting) demonstrated that, in patients with atrial fibrillation following percutaneous coronary intervention, bleeding risk was lower with dabigatran plus clopidogrel or ticagrelor (dual therapy) than warfarin plus clopidogrel or ticagrelor and aspirin (triple therapy). Dual therapy was noninferior for risk of thromboembolic events. Whether these results apply equally to patients at higher risk of ischemic events due to lesion complexity or clinical risk factors is unclear.. The primary end point was time to first major or clinically relevant nonmajor bleeding event. The composite efficacy end point was death, thromboembolic event, or unplanned revascularization. Our prespecified subgroup analysis categorized patients by presence of procedural complexity and/or clinical complexity factors at baseline. A modified dual antiplatelet therapy score categorized patients according to degree of clinical risk.. Of 2725 patients, 43.1% had clinical complexity factors alone, 9.9% procedural factors alone, 10.0% both, and 37.0% neither. Risk of the primary bleeding end point was lower in both dabigatran dual therapy groups than warfarin triple therapy groups, regardless of procedural and/or clinical lesion complexity (interaction. In patients with atrial fibrillation undergoing percutaneous coronary intervention, dabigatran 110 and 150 mg dual therapy reduced bleeding risk compared with warfarin triple therapy, with a similar risk of thromboembolic outcomes, irrespective of procedural and/or clinical complexity and modified dual antiplatelet therapy score. Registration: URL: https://clinicaltrials.gov/; Unique identifier: NCT02164864.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Dual Anti-Platelet Therapy; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Risk Assessment; Risk Factors; Stents; Thromboembolism; Ticagrelor; Time Factors; Treatment Outcome; Warfarin

Chronic kidney disease (CKD) is associated with an increased risk of acute coronary syndrome (ACS) and cardiovascular death. CKD patients suffering from ACS are exposed to an increased risk of thrombotic recurrences and a higher bleeding rate than patients with normal renal function. However, CKD patients are excluded or underrepresented in clinical trials. Therefore, determining the optimal antiplatelet strategy in this population is of utmost importance. We designed the TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome (TROUPER) trial: a prospective, controlled, multicenter, randomized trial to investigate the optimal P2Y12 antagonist in CKD patients with ACS. Patients with stage ≥3b CKD are eligible if the diagnosis of ACS is made and invasive strategy scheduled. Patients are randomized 1:1 between a control group with a 600-mg loading dose of clopidogrel followed by a 75-mg/d maintenance dose for 1 year and an experimental group with a 180-mg loading dose of ticagrelor followed by a 90-mg twice daily maintenance dose for the same duration. The primary end point is defined by the rate of major adverse cardiovascular events, including death, myocardial infarction, urgent revascularization, and stroke at 1 year. Safety will be evaluated by the bleeding rate (Bleeding Academic Research Consortium). To demonstrate the superiority of ticagrelor on major adverse cardiovascular events, we calculated that 508 patients are required. The aim of the TROUPER trial is to compare the efficacy of ticagrelor and clopidogrel in stage >3b CKD patients presenting with ACS and scheduled for an invasive strategy. RCT# NCT03357874.

Topics: Acute Coronary Syndrome; Adolescent; Adult; Aged; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Renal Insufficiency, Chronic; Secondary Prevention; Thrombosis; Ticagrelor; Young Adult

Trials have evaluated the use of clopidogrel and aspirin to prevent stroke after an ischemic stroke or transient ischemic attack (TIA). In a previous trial, ticagrelor was not better than aspirin in preventing vascular events or death after stroke or TIA. The effect of the combination of ticagrelor and aspirin on prevention of stroke has not been well studied.. We conducted a randomized, placebo-controlled, double-blind trial involving patients who had had a mild-to-moderate acute noncardioembolic ischemic stroke, with a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less (range, 0 to 42, with higher scores indicating more severe stroke), or TIA and who were not undergoing thrombolysis or thrombectomy. The patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive a 30-day regimen of either ticagrelor (180-mg loading dose followed by 90 mg twice daily) plus aspirin (300 to 325 mg on the first day followed by 75 to 100 mg daily) or matching placebo plus aspirin. The primary outcome was a composite of stroke or death within 30 days. Secondary outcomes were first subsequent ischemic stroke and the incidence of disability within 30 days. The primary safety outcome was severe bleeding.. A total of 11,016 patients underwent randomization (5523 in the ticagrelor-aspirin group and 5493 in the aspirin group). A primary-outcome event occurred in 303 patients (5.5%) in the ticagrelor-aspirin group and in 362 patients (6.6%) in the aspirin group (hazard ratio, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P = 0.02). Ischemic stroke occurred in 276 patients (5.0%) in the ticagrelor-aspirin group and in 345 patients (6.3%) in the aspirin group (hazard ratio, 0.79; 95% CI, 0.68 to 0.93; P = 0.004). The incidence of disability did not differ significantly between the two groups. Severe bleeding occurred in 28 patients (0.5%) in the ticagrelor-aspirin group and in 7 patients (0.1%) in the aspirin group (P = 0.001).. Among patients with a mild-to-moderate acute noncardioembolic ischemic stroke (NIHSS score ≤5) or TIA who were not undergoing intravenous or endovascular thrombolysis, the risk of the composite of stroke or death within 30 days was lower with ticagrelor-aspirin than with aspirin alone, but the incidence of disability did not differ significantly between the two groups. Severe bleeding was more frequent with ticagrelor. (Funded by AstraZeneca; THALES ClinicalTrial.gov number, NCT03354429.).

Topics: Aged; Aged, 80 and over; Aspirin; Disability Evaluation; Double-Blind Method; Drug Therapy, Combination; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Kaplan-Meier Estimate; Male; Middle Aged; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Stroke; Ticagrelor

Diabetes and CYP2C19 loss of function (LOF) alleles are associated with the variable antiplatelet activity of the prodrug clopidogrel. We conducted a randomized trial (NCT03613857) to compare the combined and individualized effects of diabetes and CYP2C19 polymorphisms on the antiplatelet reactivity of clopidogrel versus ticagrelor in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Patients (948, 1 year follow-up 943) were randomly allocated in a 1:1 ratio to receive either clopidogrel or ticagrelor, after PCI; patients were subdivided into 8 subgroups according to the diabetes and/or CYP2C19 allele status. The study outcomes were recurrent ACS, maximum platelet aggregation (MPA), high platelet reactivity index (PRI), and incidence of major bleeding events. Diabetic patients with LOF alleles taking clopidogrel had the highest recurrent ACS rate (6 of 33 patients) versus all other study groups (P < 0.05). However, both drugs had similar proportions of recurrent ACS in all other subgroups. Similarly, both PRI and MPA were significantly higher in the diabetic patients having LOF alleles and receiving clopidogrel versus all their study groups (P < 0.05). Nevertheless, ticagrelor caused higher rates of major bleeding versus clopidogrel (P < 0.001). PCI-treated ACS patients with diabetes and CYP2C19 LOF alleles are at a higher risk of recurrent ACS and high PRI/MPA, when treated with clopidogrel versus ticagrelor, but almost comparable outcomes are recorded in the absence of 1 or the 2 risk factors.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Clopidogrel; Cytochrome P-450 CYP2C19; Diabetes Mellitus; Egypt; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Pharmacogenomic Variants; Platelet Aggregation; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Purinergic P2Y Receptor Antagonists; Recurrence; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; Young Adult

The efficacy and safety of a reduced dose of prasugrel versus a standard dose of ticagrelor in elderly patients or those with a low body weight presenting with an acute coronary syndrome (ACS) are unknown.. To investigate the effect of an age- and weight-adapted dose of prasugrel versus a standard dose of ticagrelor in patients with ACS. (ClinicalTrials.gov: NCT01944800).. Prespecified analysis of the multicenter, randomized ISAR-REACT 5 trial.. 23 centers in Germany and Italy.. 3997 patients with ACS planned for invasive management.. Participants were randomly assigned to receive a standard dose of ticagrelor or prasugrel (reduced dose in the elderly or low-weight group and standard dose in the neither elderly nor low-weight group).. The efficacy end point was a composite of death, myocardial infarction, or stroke, and the safety end point was bleeding, both at 12 months.. In the elderly or low-weight group, the efficacy end point occurred in 12.7% of patients assigned to receive prasugrel and 14.6% of those assigned to receive ticagrelor (hazard ratio [HR], 0.82 [95% CI, 0.60 to 1.14]); in the neither elderly nor low-weight group, the efficacy end point occurred in 4.8% of patients assigned to receive prasugrel and 7.3% of those assigned to receive ticagrelor (HR, 0.65 [CI, 0.48 to 0.88];. The study is a subgroup analysis.. In elderly or low-weight patients with ACS, a reduced dose of prasugrel compared with the standard dose of ticagrelor is associated with maintained anti-ischemic efficacy while protecting these patients against the excess risk for bleeding.. German Center for Cardiovascular Research and Deutsches Herzzentrum München.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Body Weight; Drug Dosage Calculations; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor; Treatment Outcome

After percutaneous coronary intervention (PCI), patients with CYP2C19*2 or *3 loss-of-function (LOF) variants treated with clopidogrel have increased risk of ischemic events. Whether genotype-guided selection of oral P2Y12 inhibitor therapy improves ischemic outcomes is unknown.. To determine the effect of a genotype-guided oral P2Y12 inhibitor strategy on ischemic outcomes in CYP2C19 LOF carriers after PCI.. Open-label randomized clinical trial of 5302 patients undergoing PCI for acute coronary syndromes (ACS) or stable coronary artery disease (CAD). Patients were enrolled at 40 centers in the US, Canada, South Korea, and Mexico from May 2013 through October 2018; final date of follow-up was October 2019.. Patients randomized to the genotype-guided group (n = 2652) underwent point-of-care genotyping. CYP2C19 LOF carriers were prescribed ticagrelor and noncarriers clopidogrel. Patients randomized to the conventional group (n = 2650) were prescribed clopidogrel and underwent genotyping after 12 months.. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia at 12 months. A secondary end point was major or minor bleeding at 12 months. The primary analysis was in patients with CYP2C19 LOF variants, and secondary analysis included all randomized patients. The trial had 85% power to detect a minimum hazard ratio of 0.50.. Among 5302 patients randomized (median age, 62 years; 25% women), 82% had ACS and 18% had stable CAD; 94% completed the trial. Of 1849 with CYP2C19 LOF variants, 764 of 903 (85%) assigned to genotype-guided therapy received ticagrelor, and 932 of 946 (99%) assigned to conventional therapy received clopidogrel. The primary end point occurred in 35 of 903 CYP2C19 LOF carriers (4.0%) in the genotype-guided therapy group and 54 of 946 (5.9%) in the conventional therapy group at 12 months (hazard ratio [HR], 0.66 [95% CI, 0.43-1.02]; P = .06). None of the 11 prespecified secondary end points showed significant differences, including major or minor bleeding in CYP2C19 LOF carriers in the genotype-guided group (1.9%) vs the conventional therapy group (1.6%) at 12 months (HR, 1.22 [95% CI, 0.60-2.51]; P = .58). Among all randomized patients, the primary end point occurred in 113 of 2641 (4.4%) in the genotype-guided group and 135 of 2635 (5.3%) in the conventional group (HR, 0.84 [95% CI, 0.65-1.07]; P = .16).. Among CYP2C19 LOF carriers with ACS and stable CAD undergoing PCI, genotype-guided selection of an oral P2Y12 inhibitor, compared with conventional clopidogrel therapy without point-of-care genotyping, resulted in no statistically significant difference in a composite end point of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia based on the prespecified analysis plan and the treatment effect that the study was powered to detect at 12 months.. ClinicalTrials.gov Identifier: NCT01742117.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Cardiovascular Diseases; Clopidogrel; Coronary Artery Disease; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C19 Inhibitors; Female; Genotype; Genotyping Techniques; Hemorrhage; Heterozygote; Humans; Loss of Function Mutation; Male; Middle Aged; Percutaneous Coronary Intervention; Point-of-Care Testing; Precision Medicine; Purinergic P2Y Receptor Antagonists; Ticagrelor

The efficacy and safety of ticagrelor and clopidogrel in East Asian patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains uncertain. The purpose of this study was to compare the efficacy and safety of ticagrelor and clopidogrel in East Asian patients with CAD treated with PCI.. A total of 12383 patients with CAD undergoing PCI who received dual antiplatelet therapy (DAPT) were consecutively enrolled in the ticagrelor group (. Ticagrelor was associated with a lower incidence of MACCEs and an increased risk of TIMI bleeding events in East Asian patients with CAD receiving PCI.

Topics: Aged; Asian People; Clopidogrel; Coronary Artery Disease; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Preoperative Care; Ticagrelor; Treatment Outcome

Data on the comparative efficacy and safety of ticagrelor versus prasugrel in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention are limited. We assessed the efficacy and safety of ticagrelor versus prasugrel in a head-to-head comparison in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention.. In this prespecified subgroup analysis, we included 1653 patients with ST-segment-elevation myocardial infarction randomized to receive ticagrelor or prasugrel in the setting of the ISAR REACT-5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5). The primary end point was the incidence of death, myocardial infarction, or stroke at 1 year after randomization. The secondary end point was the incidence of bleeding defined as BARC (Bleeding Academic Research Consortium) type 3 to 5 bleeding at 1 year after randomization.. In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, there was no significant difference in the primary end point between prasugrel and ticagrelor. Ticagrelor was associated with a significant increase in the risk for recurrent myocardial infarction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.

Topics: Aged; Comparative Effectiveness Research; Europe; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Recurrence; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Stents; Stroke; Ticagrelor; Time Factors; Treatment Outcome

Topics: Acute Coronary Syndrome; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor

Dual antiplatelet therapy (DAPT) with aspirin and ticagrelor is recommended for at least 12 months in patients after an acute coronary syndrome (ACS). However, its underuse and premature discontinuation are common in clinical practice. We aimed to investigate the impact of a dedicated follow-up strategy with clinical visits and counselling on adherence levels to ticagrelor in patients after ACS.. PROGRESS (PROmotinG dual antiplatelet therapy adheREnce in the setting of acute coronary Syndromes) is a prospective, randomized trial enrolling 400 ACS patients treated with ticagrelor. Patients were randomized to be followed-up in a dedicated outpatient clinic (In-person follow-up group, [IN-FU], n=200), or with scheduled for phone interviews only (Telephone follow-up group [TEL-FU], n=200), to assess ticagrelor adherence and related complications. DAPT disruption was defined as an interruption of the administration of the drug due to complications or other reasons of non-adherence, and divided according to the duration into short (1-5 days), temporary (6-30 days) and permanent (≥30 days) disruption. The primary endpoint was the rate of DAPT disruption at 1-year follow-up.. The rate of ticagrelor disruption at 1 year follow-up was higher in the TEL-FU group than in the IN-FU group (19.6 vs 5.5%; p<0.0001). The IN-FU group reported a significantly lower rate of short (3.0 vs 8.5%; p=0.012) and permanent (2.0 vs 9.6%; p=0.012) disruption than TEL-FU group. The rate of major bleeding did not differ significantly between the 2 groups (p=0.450).. The PROGRESS trial showed a net reduction in DAPT disruption in patients followed-up with clinical (in-person) follow-up visits in a dedicated outpatient clinic compared with those scheduled for phone interviews only.

Topics: Acute Coronary Syndrome; Aged; Appointments and Schedules; Aspirin; Drug Administration Schedule; Dual Anti-Platelet Therapy; Female; Hemorrhage; Humans; Italy; Male; Medication Adherence; Middle Aged; Outpatient Clinics, Hospital; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Telephone; Ticagrelor; Time Factors; Treatment Outcome

To evaluate if ticagrelor, an effective platelet inhibitor without known non-responders, could inhibit growth of small abdominal aortic aneurysms (AAAs).. In this multi-centre randomized controlled trial, double-blinded for ticagrelor and placebo, acetylic salicylic acid naïve patients with AAA and with a maximum aortic diameter 35-49 mm were included. The primary outcome was mean reduction in log-transformed AAA volume growth rate (%) measured with magnetic resonance imaging (MRI) at 12 months compared with baseline. Secondary outcomes include AAA-diameter growth rate and intraluminal thrombus (ILT) volume enlargement rate. A total of 144 patients from eight Swedish centres were randomized (72 in each group). MRI AAA volume increase was 9.1% for the ticagrelor group and 7.5% for the placebo group (P = 0.205) based on intention-to-treat analysis, and 8.5% vs. 7.4% in a per-protocol analysis (P = 0.372). MRI diameter change was 2.5 mm vs. 1.8 mm (P = 0.113), US diameter change 2.3 mm vs. 2.2 mm (P = 0.778), and ILT volume change 12.9% vs. 10.4% (P = 0.590).. In this RCT, platelet inhibition with ticagrelor did not reduce growth of small AAAs. Whether the ILT has an important pathophysiological role for AAA growth cannot be determined based on this study due to the observed lack of thrombus modulating effect of ticagrelor.. The TicAAA trial is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT02070653.

Topics: Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Disease Progression; Double-Blind Method; Female; Hemorrhage; Humans; Magnetic Resonance Angiography; Male; Middle Aged; Platelet Aggregation Inhibitors; Sweden; Thrombosis; Ticagrelor; Time Factors; Treatment Outcome

To evaluate the impact of an experimental strategy [23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT)] vs. a reference regimen (12-month aspirin monotherapy following 12-month DAPT) after complex percutaneous coronary intervention (PCI).. In the present post hoc analysis of the Global Leaders trial, the primary endpoint [composite of all-cause death or new Q-wave myocardial infarction (MI)] at 2 years was assessed in patients with complex PCI, which includes at least one of the following characteristics: multivessel PCI, ≥3 stents implanted, ≥3 lesions treated, bifurcation PCI with ≥2 stents, or total stent length >60 mm. In addition, patient-oriented composite endpoint (POCE) (composite of all-cause death, any stroke, any MI, or any revascularization) and net adverse clinical events (NACE) [composite of POCE or Bleeding Academic Research Consortium (BARC) Type 3 or 5 bleeding] were explored. Among 15 450 patients included in this analysis, 4570 who underwent complex PCI had a higher risk of ischaemic and bleeding events. In patients with complex PCI, the experimental strategy significantly reduced risks of the primary endpoint [hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.48-0.85] and POCE (HR: 0.80, 95% CI: 0.69-0.93), but not in those with non-complex PCI (Pinteraction = 0.015 and 0.017, respectively). The risk of BARC Type 3 or 5 bleeding was comparable (HR: 0.97, 95% CI: 0.67-1.40), resulting in a significant risk reduction in NACE (HR: 0.80, 95% CI: 0.69-0.92; Pinteraction = 0.011).. Ticagrelor monotherapy following 1-month DAPT could provide a net clinical benefit for patients with complex PCI. However, in view of the overall neutral results of the trial, these findings of a post hoc analysis should be considered as hypothesis generating.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Case-Control Studies; Cause of Death; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; Stroke; Ticagrelor

The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain.. In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding.. A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46).. Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).

Topics: Acute Coronary Syndrome; Aged; Coronary Thrombosis; Female; Hemorrhage; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Stents; Stroke; Ticagrelor

Patients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear.. In this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with previous myocardial infarction or stroke were excluded. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria.. A total of 19,220 patients underwent randomization. The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ischemic cardiovascular events (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% vs. 8.5%; hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P = 0.04), whereas the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001), as was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P = 0.005). There was no significant difference in the incidence of fatal bleeding (0.2% vs. 0.1%; hazard ratio, 1.90; 95% CI, 0.87 to 4.15; P = 0.11). The incidence of an exploratory composite outcome of irreversible harm (death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage) was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86 to 1.02).. In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, those who received ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. (Funded by AstraZeneca; THEMIS ClinicalTrials.gov number, NCT01991795.).

Topics: Aged; Aspirin; Coronary Artery Disease; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y. We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y. For the primary analysis, 2488 patients were included: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority). The primary bleeding outcome occurred in 122 patients (9.8%) in the genotype-guided group and in 156 patients (12.5%) in the standard-treatment group (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04).. In patients undergoing primary PCI, a

Topics: Administration, Oral; Aged; Clopidogrel; Coronary Thrombosis; Cytochrome P-450 CYP2C19; Female; Genotype; Hemorrhage; Humans; Intention to Treat Analysis; Male; Middle Aged; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Precision Medicine; Purinergic P2Y Receptor Antagonists; Single-Blind Method; ST Elevation Myocardial Infarction; Stents; Ticagrelor

Monotherapy with a P2Y. In a double-blind trial, we examined the effect of ticagrelor alone as compared with ticagrelor plus aspirin with regard to clinically relevant bleeding among patients who were at high risk for bleeding or an ischemic event and had undergone PCI. After 3 months of treatment with ticagrelor plus aspirin, patients who had not had a major bleeding event or ischemic event continued to take ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. We also evaluated the composite end point of death from any cause, nonfatal myocardial infarction, or nonfatal stroke, using a noninferiority hypothesis with an absolute margin of 1.6 percentage points.. We enrolled 9006 patients, and 7119 underwent randomization after 3 months. Between randomization and 1 year, the incidence of the primary end point was 4.0% among patients randomly assigned to receive ticagrelor plus placebo and 7.1% among patients assigned to receive ticagrelor plus aspirin (hazard ratio, 0.56; 95% confidence interval [CI], 0.45 to 0.68; P<0.001). The difference in risk between the groups was similar for BARC type 3 or 5 bleeding (incidence, 1.0% among patients receiving ticagrelor plus placebo and 2.0% among patients receiving ticagrelor plus aspirin; hazard ratio, 0.49; 95% CI, 0.33 to 0.74). The incidence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke was 3.9% in both groups (difference, -0.06 percentage points; 95% CI, -0.97 to 0.84; hazard ratio, 0.99; 95% CI, 0.78 to 1.25; P<0.001 for noninferiority).. Among high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy, ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin, with no higher risk of death, myocardial infarction, or stroke. (Funded by AstraZeneca; TWILIGHT ClinicalTrials.gov number, NCT02270242.).

Topics: Aged; Aspirin; Coronary Disease; Double-Blind Method; Drug Therapy, Combination; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mortality; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Stroke; Ticagrelor

The role of aspirin as part of antiplatelet regimens in acute coronary syndromes (ACS) needs to be clarified in the context of newer potent P2Y12 antagonists.. To evaluate the benefit and risks of aspirin in addition to ticagrelor among patients with ACS beyond 1 month after percutaneous coronary intervention (PCI).. This is a nonprespecified, post hoc analysis of GLOBAL LEADERS, a randomized, open-label superiority trial comparing 2 antiplatelet treatment strategies after PCI. The trial included 130 secondary/tertiary care hospitals in different countries, with 15 991 unselected patients with stable coronary artery disease or ACS undergoing PCI. Patients had outpatient visits at 1, 3, 6, 12, 18, and 24 months after index procedure.. The experimental group received aspirin plus ticagrelor for 1 month followed by 23-month ticagrelor monotherapy; the reference group received aspirin plus either clopidogrel (stable coronary artery disease) or ticagrelor (ACS) for 12 months, followed by 12-month aspirin monotherapy. In this analysis, we examined the clinical outcomes occurring between 31 days and 365 days after randomization, specifically in patients with ACS who, within this time frame, were assigned to receive either ticagrelor alone or ticagrelor and aspirin.. The primary outcome was the composite of all-cause death or new Q-wave myocardial infarction.. Of 15 968 participants, there were 7487 patients with ACS enrolled; 3750 patients were assigned to the experimental group and 3737 patients to the reference group. Between 31 and 365 days after randomization, the primary outcome occurred in 55 patients (1.5%) in the experimental group and in 75 patients (2.0%) in the reference group (hazard ratio [HR], 0.73; 95% CI, 0.51-1.03; P = .07); investigator-reported Bleeding Academic Research Consortium-defined bleeding type 3 or 5 occurred in 28 patients (0.8%) in the experimental group and in 54 patients (1.5%) in the reference arm (HR, 0.52; 95% CI, 0.33-0.81; P = .004).. Between 1 month and 12 months after PCI in ACS, aspirin was associated with increased bleeding risk and appeared not to add to the benefit of ticagrelor on ischemic events. These findings should be interpreted as exploratory and hypothesis generating; however, they pave the way for further trials evaluating aspirin-free antiplatelet strategies after PCI.. ClinicalTrials.gov identifier: NCT01813435.

Topics: Acute Coronary Syndrome; Aspirin; Cause of Death; Continuity of Patient Care; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Hemorrhage; Humans; Internationality; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Assessment; Severity of Illness Index; Survival Analysis; Tertiary Care Centers; Ticagrelor; Time Factors; Treatment Outcome

The relationship between invasive vascular procedures and bleeding in patients with peripheral artery disease has not been well described in the literature. This post hoc analysis from the EUCLID trial (Examining Use of Ticagrelor in Peripheral Artery Disease) aimed to describe the incidence of major and minor postprocedural bleeding and characterize the timing and severity of bleeding events relative to the procedure.. EUCLID was a multicenter, randomized controlled trial of 13 885 patients with symptomatic peripheral artery disease that tested the efficacy and safety of ticagrelor compared with clopidogrel for the prevention of major adverse cardiovascular events. A total of 2661 patients underwent 3062 coronary revascularization, peripheral revascularization, and amputation during the study. The primary safety end point was Thrombolysis in Myocardial Infarction major or minor bleeding. All bleeding events were formally adjudicated by a clinical end point classification group.. Major bleeding events most often occurred ≤7 days following the procedure. The incidence of Thrombolysis in Myocardial Infarction major or minor bleeding ≤7 days following peripheral revascularization (3.3%; 95% CI, 2.5%-4.1%) was similar to rates after coronary revascularization (4.0%; 95% CI, 2.6%-5.4%) and lower extremity amputation (2.3%; 95% CI, 0.8%-3.8%). The severity of bleeding events (as graded by drop in hemoglobin, need for transfusion, bleeding in a critical location, and fatal bleeding) was also similar following peripheral, coronary revascularization, and lower extremity amputation.. The incidence of Thrombolysis in Myocardial Infarction major/minor bleeding following peripheral revascularization is comparable to rates after coronary revascularization and lower extremity amputation, and the majority of bleeding events occur within 7 days following the procedure. The severity of periprocedural bleeding is also similar after procedures, with the most frequently adjudicated reason being a drop in hemoglobin ≥2 g/dL. Future studies should be performed to enhance our understanding of bleeding risk related to revascularization and amputation procedures in peripheral artery disease patients.

Topics: Aged; Amputation, Surgical; Clopidogrel; Double-Blind Method; Endovascular Procedures; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Revascularization; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Data on optimal antiplatelet treatment regimens in patients who undergo multivessel percutaneous coronary intervention (PCI) are sparse.. This post hoc study investigated the impact of an experimental strategy (1-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus a reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) according to multivessel PCI.. The GLOBAL LEADERS trial is a prospective, multicenter, open-label, randomized controlled trial, allocating all-comer patients in a 1:1 ratio to either the experimental strategy or the reference regimen. The primary endpoint was the composite of all-cause death or new Q-wave myocardial infarction at 2 years. The secondary safety endpoint was Bleeding Academic Research Consortium type 3 or 5 bleeding.. Long-term ticagrelor monotherapy following 1-month DAPT can favorably balance ischemic and bleeding risks in patients with multivessel PCI. These findings should be interpreted as hypothesis-generating and need to be replicated in future dedicated randomized trials. (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation; NCT01813435).

Topics: Aged; Aspirin; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Patient Safety; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Risk; Stroke; Thrombosis; Ticagrelor; Treatment Outcome

The aim of this study was to assess if prior oral anticoagulant agent (OAC) use modifies the lower bleeding risk observed with dabigatran dual therapy (dabigatran twice daily plus a P2Y. In the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial, the primary outcome of major bleeding or clinically relevant nonmajor bleeding was lower with dabigatran dual therapy versus warfarin triple therapy in patients with atrial fibrillation who underwent PCI.. A total of 2,725 patients were randomized to dual therapy with dabigatran (110 or 150 mg twice daily) plus clopidogrel or ticagrelor or triple therapy with warfarin plus aspirin and clopidogrel or ticagrelor. Subgroup analysis compared risk for major bleeding or clinically relevant nonmajor bleeding and a composite thromboembolic endpoint in patients with prior OAC use and in those who were OAC treatment naive.. Risk for major bleeding or clinically relevant nonmajor bleeding was reduced with both dabigatran dual therapies compared with warfarin triple therapy in both the prior OAC use group (hazard ratios: 0.58 [95% confidence interval (CI): 0.42 to 0.81] and 0.61 [95% CI: 0.41 to 0.92] with 110 and 150 mg dabigatran, respectively) and the OAC-naive group (hazard ratios: 0.49 [95% CI: 0.38 to 0.63] and 0.76 [95% CI: 0.59 to 0.97] with 110 and 150 mg dabigatran) (p for interaction = 0.42 and 0.37, 110 and 150 mg dabigatran, respectively). The risk for thromboembolic events seemed similar with dabigatran dual therapy (both doses) and warfarin triple therapy across subgroups.. Bleeding risk was reduced with dabigatran dual therapy versus warfarin triple therapy in patients with atrial fibrillation after PCI, regardless of whether they were prior OAC users or OAC treatment naive. These results suggest that it is also safe to switch patients on OAC pre-PCI to dabigatran dual therapy post-PCI.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Drug Substitution; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; Warfarin

The aim of this study was to evaluate dabigatran dual therapy versus warfarin triple therapy in patients with or without diabetes mellitus in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial.. It is unclear whether dual therapy is as safe and efficacious as triple therapy in patients with atrial fibrillation with diabetes following percutaneous coronary intervention.. In RE-DUAL PCI, 2,725 patients with atrial fibrillation (993 with diabetes) who had undergone PCI were assigned to warfarin triple therapy (warfarin, clopidogrel or ticagrelor, and aspirin) or dabigatran dual therapy (dabigatran 110 mg or 150 mg twice daily and clopidogrel or ticagrelor). Median follow-up was 13 months. The primary outcome was the composite of major bleeding or clinically relevant nonmajor bleeding, and the main efficacy outcome was the composite of death, thromboembolic events, or unplanned revascularization.. Among patients with diabetes, the incidence of major bleeding or clinically relevant nonmajor bleeding was 15.2% in the dabigatran 110 mg dual therapy group versus 27.5% in the warfarin triple therapy group (hazard ratio [HR]: 0.48; 95% confidence interval [CI] 0.35 to 0.67) and 23.8% in the dabigatran 150 mg dual therapy group versus 25.1% in the warfarin triple therapy group (HR: 0.87; 95% CI: 0.62 to 1.22). Risk for major bleeding or clinically relevant nonmajor bleeding was also reduced with both dabigatran doses among patients without diabetes (dabigatran 110 mg dual therapy: HR: 0.54; 95% CI: 0.42 to 0.70; dabigatran 150 mg dual therapy: HR: 0.63; 95% CI: 0.48 to 0.83). Risk for the efficacy endpoint was comparable between treatment groups for both patients with and those without diabetes. No interaction between treatment and diabetes subgroup could be observed, either for bleeding or for composite efficacy endpoints.. In this subgroup analysis, dabigatran dual therapy had a lower risk for bleeding and a comparable rate of the efficacy endpoint compared with warfarin triple therapy in patients with atrial fibrillation with or without diabetes following percutaneous coronary intervention.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Diabetes Mellitus; Drug Substitution; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; Warfarin

The optimal anti-coagulation strategy for patients with non-ST-elevation myocardial infarction treated with percutaneous coronary intervention is unclear in contemporary clinical practice of radial access and potent P2Y12-inhibitors. The aim of this study was to investigate whether bivalirudin was superior to heparin monotherapy in patients with non-ST-elevation myocardial infarction without routine glycoprotein IIb/IIIa inhibitor use.. In a large pre-specified subgroup of the multicentre, prospective, randomised, registry-based, open-label clinical VALIDATE-SWEDEHEART trial we randomised patients with non-ST-elevation myocardial infarction undergoing percutaneous coronary intervention, treated with ticagrelor or prasugrel, to bivalirudin or heparin monotherapy with no planned use of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention. The primary endpoint was the rate of a composite of all-cause death, myocardial infarction or major bleeding within 180 days.. Bivalirudin as compared to heparin during percutaneous coronary intervention for non-ST-elevation myocardial infarction did not reduce the composite of all-cause death, myocardial infarction or major bleeding in non-ST-elevation myocardial infarction patients receiving current recommended treatments with modern P2Y12-inhibitors and predominantly radial access.

Topics: Aged; Anticoagulants; Antithrombins; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Recombinant Proteins; Stents; Sweden; Thrombosis; Ticagrelor

Current treatment guidelines do not recommend different antiplatelet treatments for patients in different coronary risk categories; nor do they consider ethnic differences in responses to individual drugs.. We performed a prospective, single-blind, randomized, comparative study of Taiwanese patients with stable angina and scheduled stent implantation for intermediate-to-highly complex coronary lesions and compared the platelet reactivity unit (PRU) levels and 24-month outcomes of groups receiving three different antiplatelet treatments.. Patients (N = 334) were randomized into three treatment groups (aspirin + clopidogrel, aspirin + ticagrelor, or aspirin + clopidogrel + cilostazol) for 6 months of treatment and were then switched to aspirin only. PRU levels were determined 24 h, 7 days, and 1 month after stent implantation. Clinical outcomes and adverse events were recorded over 24 months.. Clopidogrel treatment reached full effect after 1 month. Ticagrelor decreased PRU levels more than did clopidogrel but often to levels that increased the risk of hemorrhage. The addition of cilostazol to clopidogrel decreased PRU levels earlier and more strongly than clopidogrel alone but not as strongly as did ticagrelor. Ticagrelor treatment caused fewer major adverse cardiovascular events (MACEs) and more episodes of minor bleeding than the other two treatments.. Clopidogrel appears safer than ticagrelor in Taiwanese patients with stable angina after stent implantation for intermediate-to-highly complex coronary lesions. The addition of cilostazol to clopidogrel may provide a more rapid decrease in PRU to therapeutic levels without increasing the risk of hemorrhage.. NCT02101411.

Topics: Aged; Aspirin; Blood Platelets; Cilostazol; Clopidogrel; Diamines; Female; Hemorrhage; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Purinergic P2Y Receptor Antagonists; Single-Blind Method; Taiwan; Thiazoles; Ticagrelor

Background and Purpose- Recurrent ischemia risk is high in the acute period after cerebral ischemic events. Effects of antiplatelet agents may vary by time to loading dose (TLD). We explored the risk of recurrent events and safety and efficacy of ticagrelor versus aspirin in relation to TLD. Methods- We randomized 13 199 patients with noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to 90-day ticagrelor or aspirin treatment within 24 hours of symptom onset. For this analysis, 13 126 patients were categorized by TLD as <12 hours or ≥12 hours from start of index event. The primary end point was the composite of stroke, myocardial infarction, or death within 90 days. Major bleeding was the primary safety end point. Results- TLD was <12 hours in 4403 (33.5%) and ≥12 hours in 8723 (66.5%). The Kaplan-Meier% for the primary end point for all patients with TLD<12 hours was 7.5% versus 6.9% in TLD≥12 hours. Among patients with TLD<12 hours, the primary end point occurred in 147/2196 (6.8%) randomized to ticagrelor and in 184/2207 (8.3%) randomized to aspirin (hazard ratio, 0.79; 95% CI, 0.64-0.98; P=0.036). Among patients with TLD≥12 hours, the primary end point occurred in 6.7% patients randomized to ticagrelor versus 7.0% to aspirin (hazard ratio, 0.95; 95% CI, 0.81-1.12; P=0.55). There was no significant treatment-by-TLD interaction. Major bleeding rates were comparable on ticagrelor and aspirin, regardless of TLD. Conclusions- The event rate for the primary end point was higher in patients treated early (<12 hours) versus later (≥12 hours). In this exploratory analysis, a larger numerical difference in the primary end point was observed among patients on ticagrelor than on aspirin when TLD was <12 hours compared with ≥12 hours, although the interaction terms for treatment-by-TLD were not significant. For major bleeding, no relation to TLD was observed. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01994720.

Topics: Aged; Aged, 80 and over; Aspirin; Endpoint Determination; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Recurrence; Risk; Stroke; Ticagrelor; Time-to-Treatment

After percutaneous coronary intervention (PCI) in patients with atrial fibrillation, safety and efficacy with dabigatran dual therapy were evaluated in pre-specified subgroups of patients undergoing PCI due to acute coronary syndrome (ACS) or elective PCI, and those receiving ticagrelor or clopidogrel treatment.. In the RE-DUAL PCI trial, 2725 patients were randomized to dabigatran 110 mg or 150 mg with P2Y12 inhibitor, or warfarin with P2Y12 inhibitor and aspirin. Mean follow-up was 14 months, 50.5% had ACS, and 12% received ticagrelor. The risk of the primary endpoint, major or clinically relevant non-major bleeding event, was reduced with both dabigatran dual therapies vs. warfarin triple therapy in patients with ACS [hazard ratio (95% confidence interval), 0.47 (0.35-0.63) for 110 mg and 0.67 (0.50-0.90) for 150 mg]; elective PCI [0.57 (0.43-0.76) for 110 mg and 0.76 (0.56-1.03) for 150 mg]; receiving ticagrelor [0.46 (0.28-0.76) for 110 mg and 0.59 (0.34-1.04) for 150 mg]; or clopidogrel [0.51 (0.41-0.64) for 110 mg and 0.73 (0.58-0.91) for 150 mg], all interaction P-values >0.10. Overall, dabigatran dual therapy was comparable to warfarin triple therapy for the composite endpoint of death, myocardial infarction, stroke, systemic embolism, or unplanned revascularization, with minor variations across the subgroups, all interaction P-values >0.10.. The benefits of both dabigatran 110 mg and 150 mg dual therapy compared with warfarin triple therapy in reducing bleeding risks were consistent across subgroups of patients with or without ACS, and patients treated with ticagrelor or clopidogrel.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Aspirin; Atrial Fibrillation; Case-Control Studies; Clopidogrel; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Dual Anti-Platelet Therapy; Elective Surgical Procedures; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Stroke; Ticagrelor; Warfarin

In the RE-DUAL PCI trial of patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI), dabigatran dual therapy (110 or 150 mg bid, plus clopidogrel or ticagrelor) reduced International Society on Thrombosis and Haemostasis bleeding events compared with warfarin triple therapy, with noninferiority in overall thromboembolic events. This analysis assessed outcomes in relation to patient bleeding and stroke risk profiles, based on the modified HAS-BLED and CHA. The primary endpoint, major bleeding event (MBE) or clinically relevant nonmajor bleeding event (CRNMBE), was compared across study arms in patients categorized by modified HAS-BLED score 0-2 or ≥3. The composite endpoint of death, thromboembolic event, and unplanned revascularization rates was compared in patients categorized by CHA. Risk of MBE or CRNMBE was lower with dabigatran dual therapy (both doses) versus warfarin triple therapy, irrespective of modified HAS-BLED category (treatment-by-subgroup interaction P-value 0.584 and 0.273 for dabigatran 110 and 150 mg dual therapy, respectively, vs warfarin). Risk of the composite thromboembolic endpoint was similar across CHA. Dabigatran dual therapy reduced bleeding events irrespective of bleeding risk category and demonstrated similar efficacy regardless of stroke risk category when compared with warfarin triple therapy.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Equivalence Trials as Topic; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Risk Assessment; Stroke; Thromboembolism; Ticagrelor; Warfarin

High on-treatment platelet reactivity (HTPR) after clopidogrel administration in patients with acute coronary syndrome (ACS) has been associated with an increased risk of adverse events. Our previous studies reported that half-dose ticagrelor provides a similar inhibitory effect on adenosine diphosphate (ADP)-induced platelet aggregation as standard-dose ticagrelor, but half-dose of ticagrelor has not been studied in Chinese ACS patients with HTPR. This study aimed to compare the antiplatelet action of half-dose ticagrelor with high-dose clopidogrel in ACS patients with HTPR.. In this single-center randomized controlled trial, 80 (of 418 screened, 19.13%) ACS patients with HTPR while on clopidogrel were randomized to either half-dose ticagrelor (90 mg LD, then 45 mg twice daily) or high-dose clopidogrel (150 mg once daily). Platelet function was assessed by thromboelastography (TEG) and light transmission aggregometry (LTA), and adverse events were monitored throughout the study for 30 days.. The ADP-induced platelet inhibition rate (IR) as measured by TEG was significantly higher for half-dose ticagrelor compared with high-dose clopidogrel (70.40% [61.10%-91.70%] vs. 44.25% [34.67%-79.07%], p = 0.001). The repeated HTPR rate was dramatically higher for high-dose clopidogrel compared with half-dose ticagrelor (6 of 32, 18.75% vs. 1 of 35, 2.85%; p = 0.04). No patients in either treatment group exhibited a major bleeding event or other adverse events.. In ACS patients with HTPR, half-dose ticagrelor is more effective than high-dose clopidogrel in reducing platelet reactivity (NCT03062462).

Topics: Acute Coronary Syndrome; Aged; Asian People; Clopidogrel; Dose-Response Relationship, Drug; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Ticagrelor; Treatment Outcome

Adjudication of endpoints is a standard procedure in cardiovascular clinical trials. However, several studies indicate that the benefit of adjudication in estimating treatment effect may be limited.. This post hoc analysis of SOCRATES (NCT01994720) compared the treatment effects and investigated the agreement of clinical event assessment by site investigators and independent adjudicators.. SOCRATES compared ticagrelor and aspirin in 13,199 patients with acute minor stroke or high-risk transient ischemic attack. The primary endpoint was stroke, myocardial infarction, or death. Stroke was the major component of the primary endpoint and a secondary endpoint. The endpoints were adjudicated by a blinded independent committee. We compared the treatment effect on the primary endpoint and stroke alone based on the investigators' and adjudicators' assessments, and investigated the agreement rate on the stroke endpoint and major hemorrhages.. The hazard ratios (95% confidence interval) for ticagrelor versus aspirin therapy for the primary endpoint were 0.89 (0.78-1.01) when calculated on adjudicator-assessed events and 0.88 (0.78-1.00) for investigator-assessed events. The hazard ratios (95% confidence intervals) for stroke were 0.86 (0.75-0.99) based on the adjudicators' diagnoses and 0.85 (0.75-0.97) based on the investigators' diagnoses. The overall agreement between adjudicator- and investigator-diagnosed stroke was 91%, and for major hemorrhages was 88%.. In SOCRATES, there was no clinically meaningful difference in the estimated treatment effect, on either the primary endpoint or stroke, by using investigator- or adjudicator-assessed events. Double-blind treatment outcome studies with stroke endpoints may not benefit from adjudication.. ClinicalTrials.gov Identifier: NCT01994720.

Topics: Aspirin; Hemorrhage; Humans; Ischemic Attack, Transient; Mortality; Myocardial Infarction; Observer Variation; Platelet Aggregation Inhibitors; Proportional Hazards Models; Research Personnel; Secondary Prevention; Stroke; Ticagrelor

Heart failure (HF) following acute coronary syndromes (ACS) is associated with worse prognosis; however, the efficacy and safety of ticagrelor in patients with HF and if ticagrelor influences the risk of new-onset HF are unknown.. We examined the efficacy and safety of ticagrelor compared to clopidogrel in patients with ACS in the randomized PLATelet inhibition and patient Outcomes (PLATO) trial subdivided by strata: (1) previous HF and/or clinical signs of HF on admission or (2) no HF on admission. The primary outcome was the combination of cardiovascular death, myocardial infarction, or stroke evaluated by multivariable Cox regression models. The safety outcome was major bleeding. New-onset HF was defined as an HF event after discharge in patients without previous HF.. Data were available in 18,556 patients, whom 2,862 (15.4%) patients had HF, including 1,584 (8.5%) patients with previous HF. Patients randomized to ticagrelor had lower risk of the composite end point regardless of HF status: hazard ratio (HR) 0.87 (95% CI: 0.73-1.03) in patients with HF and HR 0.84 (95% CI: 0.75-0.93) in patients with no HF (P = .76). Corresponding HR for major bleeding were HR 1.08 (95% CI: 0.87-1.34) and HR 1.03 (95% CI: 0.94-1.14) (P = .71). There was no difference in new-onset HF at 12 months between patients randomized to ticagrelor (4.1%, n = 278) or clopidogrel (4.0%, n = 276).. In patients with ACS, ticagrelor is more efficacious in protecting against new ischemic events and mortality than clopidogrel irrespective of the presence of HF. There is no difference between ticagrelor or clopidogrel treatment in new-onset HF post-ACS.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Female; Heart Failure; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Proportional Hazards Models; Stroke; Ticagrelor

Antiplatelet therapy combining aspirin and clopidogrel is considered to be a key intervention for acute ischaemic minor stroke (AIMS) and transient ischaemic attack (TIA). However, the interindividual variability in response to clopidogrel resulting from the polymorphisms in clopidogrel metabolism-related genes has greatly limited its efficacy. To date, there are no reports on individualised antiplatelet therapy for AIMS and TIA based on the genetic testing and clinical features. Therefore, we conduct this randomised controlled trial to validate the hypothesis that the individualised antiplatelet therapy selected on the basis of a combination of genetic information and clinical features would lead to better clinical outcomes compared with the standard care based only on clinical features in patients with AIMS or TIA.. This trial will recruit 2382 patients with AIMS or TIA who meet eligibility criteria. Patients are randomly assigned in a 1:1 ratio to pharmacogenetic group and standard group. Both groups receive a loading dose of 300 mg aspirin and 300 mg clopidogrel on day 1, followed by 100 mg aspirin per day on days 2-365. The P2Y12 receptor antagonist is selected by the clinician according to the genetic information and clinical features for pharmacogenetic group and clinical features for the standard group on days 2-21. The primary efficacy endpoint is a new stroke event (ischaemic or haemorrhagic) that happens within 1 year. The secondary efficacy endpoint is analysed as the individual or composite outcomes of the new clinical vascular event (ischaemic stroke, haemorrhagic stroke, myocardial infarction or vascular death). Baseline characteristics and outcomes after treatment will be evaluated.. This protocol has been approved by the ethics committee of Yangpu Hospital, Tongji University School of Medicine (No. LL-2018-KY-012). We will submit the results of this trial for publication in a peer-reviewed journal.. ChiCTR1800019911; Pre-results.

Topics: Aspirin; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Therapy, Combination; Hemorrhage; Humans; Ischemic Attack, Transient; Pharmacogenomic Testing; Platelet Aggregation Inhibitors; Secondary Prevention; Stroke; Ticagrelor

Physician behavior in response to knowledge of a patient's CYP2C19 clopidogrel metabolizer status is unknown.. To investigate the association of mandatory reporting of CYP2C19 pharmacogenomic testing, provided to investigators with no direct recommendations on how to use these results, with changes in P2Y12 inhibitor use, particularly clopidogrel, in the Randomized Trial to Compare the Safety of Rivaroxaban vs Aspirin in Addition to Either Clopidogrel or Ticagrelor in Acute Coronary Syndrome (GEMINI-ACS-1) clinical trial.. The GEMINI-ACS-1 trial compared rivaroxaban, 2.5 mg twice daily, with aspirin, 100 mg daily, plus open-label clopidogrel or ticagrelor (provided), in patients with recent acute coronary syndromes (ACS). The trial included 371 clinical centers in 21 countries and 3037 patients with ACS. Data were analyzed between May 2017 and February 2019.. Investigators were required to prestipulate their planned response to CYP2C19 metabolizer status. In response to a regulatory mandate, results for all patients were reported to investigators approximately 1 week after randomization.. Reasons for switching P2Y12 inhibitors and occurrence of bleeding and ischemic events were collected.. Of 3037 patients enrolled (mean [SD] age, 62.8 [9.0] years; 2275 men [74.9%], and 2824 white race/ethnicity [93.0%]), investigators initially treated 1704 (56.1%) with ticagrelor and 1333 (43.9%) with clopidogrel. Investigators prestipulated that they would use CYP2C19 metabolizer status to change P2Y12 inhibitor in 48.5% of genotyped clopidogrel-treated patients (n = 642 of 1324) and 5.5% of genotyped ticagrelor-treated patients (n = 93 of 1692). P2Y12 inhibitor switching for any reason occurred in 197 patients and was more common in patients treated with ticagrelor (146 of 1704 [8.6%]) compared with clopidogrel (51 of 1333 [3.8%]). Of patients initially treated with ticagrelor, only 1 (0.1% overall; 0.7% of all who switched) was switched based on CYP2C19 status. Of patients initially treated with clopidogrel, 23 (1.7% overall,;45.1% of all who switched) were switched owing to metabolizer status. Of 48 patients (3.6%) with reduced metabolizer status treated initially with clopidogrel, 15 (31.3%) were switched based on metabolizer status, including 48.1% (13 of 27) in which switching was prestipulated.. Physicians were evenly split on how to respond to knowledge of CYP2C19 metabolizer status in clopidogrel-treated patients. Mandatory provision of this information rarely prompted P2Y12 inhibitor switching overall, including a minority of patients with reduced metabolizer status. These findings highlight the clinical equipoise among physicians regarding use of this information and the reluctance to use information from routine genotyping in the absence of definitive clinical trial data demonstrating the efficacy of this approach.. ClinicalTrials.gov identifier: NCT02293395.

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Administration Schedule; Drug Substitution; Drug Therapy, Combination; Hemorrhage; Humans; Ischemia; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Rivaroxaban; Ticagrelor

'Real world' bleeding in patients exposed to different regimens of dual antiplatelet therapy (DAPT) and triple therapy (TT, DAPT plus an anticoagulant) have a clinical and economic impact but have not been previously quantified.. We will use linked Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) data to assemble populations eligible for three 'target trials' in patient groups: percutaneous coronary intervention (PCI); coronary artery bypass grafting (CABG); conservatively managed (medication only) acute coronary syndrome (ACS). Patients ≥18 years old will be eligible if, in CPRD records, they have: ≥1 year of data before the index event; no prescription for DAPT or anticoagulants in the preceding 3 months; a prescription for aspirin or DAPT within 2 months after discharge from the index event. The primary outcome will be any bleeding event (CPRD or HES) up to 12 months after the index event. We will estimate adjusted HR for time to first bleeding event comparing: aspirin and clopidogrel (reference) versus aspirin and prasugrel or aspirin and ticagrelor after PCI; and aspirin (reference) versus aspirin and clopidogrel after CABG and ACS. We will describe rates of bleeding in patients prescribed TT (DAPT plus an anticoagulant). Potential confounders will be identified systematically using literature review, semistructured interviews with clinicians and a short survey of clinicians. We will conduct sensitivity analyses addressing the robustness of results to the study's main limitation-that we will not be able to identify the intervention group for patients whose bleeding event occurs before a DAPT prescription in CPRD.. This protocol was approved by the Independent Scientific Advisory Committee for the UK Medicines and Healthcare Products Regulatory Agency Database Research (protocol 16_126R) and the South West Cornwall and Plymouth Research Ethics Committee (17/SW/0092). The findings will be presented in peer-reviewed journals, lay summaries and briefing papers to commissioners/other stakeholders.. 76607611; Pre-results.

Topics: Acute Coronary Syndrome; Adult; Anticoagulants; Aspirin; Clopidogrel; Coronary Artery Bypass; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor; United Kingdom

Elevated levels of osteoprotegerin, a secreted tumor necrosis factor-related molecule, might be associated with adverse outcomes in patients with coronary artery disease. We measured plasma osteoprotegerin concentrations on hospital admission, at discharge, and at 1 and 6 months after discharge in a predefined subset (n=5135) of patients with acute coronary syndromes in the PLATO (Platelet Inhibition and Patient Outcomes) trial.. The associations between osteoprotegerin and the composite end point of cardiovascular death, nonprocedural spontaneous myocardial infarction or stroke, and non-coronary artery bypass grafting major bleeding during 1 year of follow-up were assessed by Cox proportional hazards models. Event rates of the composite end point per increasing quartile groups at baseline were 5.2%, 7.5%, 9.2%, and 11.9%. A 50% increase in osteoprotegerin level was associated with a hazard ratio (HR) of 1.31 (95% confidence interval [CI], 1.21-1.42) for the composite end point but was not significant in adjusted analysis (ie, clinical characteristics and levels of C-reactive protein, troponin T, NT-proBNP [N-terminal pro-B-type natriuretic peptide], and growth differentiation factor-15). The corresponding rates of non-coronary artery bypass grafting major bleeding were 2.4%, 2.2%, 3.8%, and 7.2%, with an unadjusted HR of 1.52 (95% CI, 1.36-1.69), and a fully adjusted HR of 1.26 (95% CI, 1.09-1.46). The multivariable association between the osteoprotegerin concentrations and the primary end point after 1 month resulted in an HR of 1.09 (95% CI, 0.89-1.33); for major bleeding after 1 month, the HR was 1.33 (95% CI, 0.91-1.96).. In patients with acute coronary syndrome treated with dual antiplatelet therapy, osteoprotegerin was an independent marker of major bleeding but not of ischemic cardiovascular events. Thus, high osteoprotegerin levels may be useful in increasing awareness of increased bleeding risk in patients with acute coronary syndrome receiving antithrombotic therapy.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Biomarkers; Clopidogrel; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Osteoprotegerin; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; Up-Regulation

To determine whether fibrin clot properties are associated with clinical outcomes following acute coronary syndrome (ACS).. Plasma samples were collected at hospital discharge from 4354 ACS patients randomized to clopidogrel or ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial. A validated turbidimetric assay was employed to study plasma clot lysis time and maximum turbidity (a measure of clot density). One-year rates of cardiovascular (CV) death, spontaneous myocardial infarction (MI) and PLATO-defined major bleeding events were assessed after sample collection. Hazard ratios (HRs) were estimated using Cox proportional hazards models. After adjusting for CV risk factors, each 50% increase in lysis time was associated with CV death/spontaneous MI [HR 1.17, 95% confidence interval (CI) 1.05-1.31; P < 0.01] and CV death alone (HR 1.36, 95% CI 1.17-1.59; P < 0.001). Similarly, each 50% increase in maximum turbidity was associated with increased risk of CV death (HR 1.24, 95% CI 1.03-1.50; P = 0.024). After adjustment for other prognostic biomarkers (leukocyte count, high-sensitivity C-reactive protein, high-sensitivity troponin T, cystatin C, N-terminal pro B-type natriuretic peptide, and growth differentiation factor-15), the association with CV death remained significant for lysis time (HR 1.2, 95% CI 1.01-1.42; P = 0.042) but not for maximum turbidity. These associations were consistent regardless of randomized antiplatelet treatment (all interaction P > 0.05). Neither lysis time nor maximum turbidity was associated with major bleeding events.. Fibrin clots that are resistant to lysis independently predict adverse outcome in ACS patients. Novel therapies targeting fibrin clot properties might be a new avenue for improving prognosis in patients with ACS.

Topics: Acute Coronary Syndrome; Aged; Blood Coagulation; Clopidogrel; Double-Blind Method; Female; Fibrin; Fibrin Clot Lysis Time; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Ticagrelor is an orally administered, reversibly binding, direct-acting P2Y. Patients hospitalized with an ACS received ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) plus low-dose aspirin (75-100 mg/day) for up to 12 months. Safety was evaluated via PLATO-defined bleeding events, adverse events (AEs), serious AEs, and laboratory measurements. The incidence of major CV events was also evaluated.. The safety population included 2001 patients. During ticagrelor treatment, 426 (21.3%) patients had at least one PLATO-defined bleeding AE, mainly minimal bleedings (n = 333). Major bleeding events occurred in 27 (1.3%) patients, including fatal/life-threatening bleeding in 17 (0.8%) patients and other major bleeding in 11 (0.5%) patients, with a Kaplan-Meier estimate of patients with the event (95% CI) of 1.6% (1.1-2.3%). In total, 784 (39.2%) patients had at least one non-bleeding AE, the majority of which were mild in severity. The composite endpoint of CV death, myocardial infarction, and stroke occurred in 83 (4.1%) patients.. Ticagrelor plus low-dose aspirin for up to 1 year was associated with a low rate of major bleeding events and a low incidence of major CV events (CV death, myocardial infarction, stroke) in Chinese patients with ACS. The overall safety profile of ticagrelor in this population was in line with current prescribing information.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Aspirin; China; Drug Therapy, Combination; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Risk Factors; Stroke; Ticagrelor; Time Factors; Treatment Outcome

The bleeding safety of ticagrelor in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy remains uncertain.. To evaluate the short-term safety of ticagrelor when compared with clopidogrel in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy.. We conducted a multicenter, randomized, open-label with blinded end point adjudication trial that enrolled 3799 patients (younger than 75 years) with ST-segment elevation myocardial infarction receiving fibrinolytic therapy in 152 sites from 10 countries from November 2015 through November 2017. The prespecified upper boundary for noninferiority for bleeding was an absolute margin of 1.0%.. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter). Patients were randomized with a median of 11.4 hours after fibrinolysis, and 90% were pretreated with clopidogrel.. The primary outcome was thrombolysis in myocardial infarction (TIMI) major bleeding through 30 days.. The mean (SD) age was 58.0 (9.5) years, 2928 of 3799 patients (77.1%) were men, and 2177 of 3799 patients (57.3%) were white. At 30 days, TIMI major bleeding had occurred in 14 of 1913 patients (0.73%) receiving ticagrelor and in 13 of 1886 patients (0.69%) receiving clopidogrel (absolute difference, 0.04%; 95% CI, -0.49% to 0.58%; P < .001 for noninferiority). Major bleeding defined by the Platelet Inhibition and Patient Outcomes criteria and by the Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 23 patients (1.20%) in the ticagrelor group and in 26 patients (1.38%) in the clopidogrel group (absolute difference, -0.18%; 95% CI, -0.89% to 0.54; P = .001 for noninferiority). The rates of fatal (0.16% vs 0.11%; P = .67) and intracranial bleeding (0.42% vs 0.37%; P = .82) were similar between the ticagrelor and clopidogrel groups, respectively. Minor and minimal bleeding were more common with ticagrelor than with clopidogrel. The composite of death from vascular causes, myocardial infarction, or stroke occurred in 76 patients (4.0%) treated with ticagrelor and in 82 patients (4.3%) receiving clopidogrel (hazard ratio, 0.91; 95% CI, 0.67-1.25; P = .57).. In patients younger than 75 years with ST-segment elevation myocardial infarction, delayed administration of ticagrelor after fibrinolytic therapy was noninferior to clopidogrel for TIMI major bleeding at 30 days.. clinicaltrials.gov Identifier: NCT02298088.

Topics: Aged; Clopidogrel; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Ticagrelor

The effect of ticagrelor with or without aspirin on saphenous vein graft patency in patients undergoing coronary artery bypass grafting (CABG) is unknown.. To compare the effect of ticagrelor + aspirin or ticagrelor alone vs aspirin alone on saphenous vein graft patency 1 year after CABG.. Randomized, multicenter, open-label, clinical trial among 6 tertiary hospitals in China. Eligible patients were aged 18 to 80 years with indications for elective CABG. Patients requiring urgent revascularization, concomitant cardiac surgery, dual antiplatelet or vitamin K antagonist therapy post-CABG, and who were at risk of serious bleeding were excluded. From July 2014 until November 2015, 1256 patients were identified and 500 were enrolled. Follow-up was completed in January 2017.. Patients were randomized (1:1:1) to start ticagrelor (90 mg twice daily) + aspirin (100 mg once daily) (n = 168), ticagrelor (90 mg twice daily) (n = 166), or aspirin (100 mg once daily) (n = 166) within 24 hours post-CABG. Neither patients nor treating physicians were blinded to allocation.. Primary outcome was saphenous vein graft patency 1 year after CABG (FitzGibbon grade A) adjudicated independently by a committee blinded to allocation. Saphenous vein graft patency was assessed by multislice computed tomographic angiography or coronary angiography.. Among 500 randomized patients (mean age, 63.6 years; women, 91 [18.2%]), 461 (92.2%) completed the trial. Saphenous vein graft patency rates 1 year post-CABG were 88.7% (432 of 487 vein grafts) with ticagrelor + aspirin; 82.8% (404 of 488 vein grafts) with ticagrelor alone; and 76.5% (371 of 485 vein grafts) with aspirin alone. The difference between ticagrelor + aspirin vs aspirin alone was statistically significant (12.2% [95% CI, 5.2% to 19.2%]; P < .001), whereas the difference between ticagrelor alone vs aspirin alone was not statistically significant (6.3% [95% CI, -1.1% to 13.7%]; P = .10). Five major bleeding episodes occurred during 1 year of follow-up (3 with ticagrelor + aspirin; 2 with ticagrelor alone).. Among patients undergoing elective CABG with saphenous vein grafting, ticagrelor + aspirin significantly increased graft patency after 1 year vs aspirin alone; there was no significant difference between ticagrelor alone and aspirin alone. Further research with more patients is needed to assess comparative bleeding risks.. clinicaltrials.gov Identifier: NCT02201771.

Topics: Adenosine; Adult; Aged; Aspirin; Coronary Artery Bypass; Coronary Restenosis; Drug Therapy, Combination; Elective Surgical Procedures; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Saphenous Vein; Ticagrelor; Vascular Patency

The prospective observational CHANGE DAPT study compared clopidogrel versus ticagrelor-based dual antiplatelet (DAPT) regimens in consecutive patients with acute coronary syndrome (ACS), treated with percutaneous coronary intervention (PCI) with contemporary drug-eluting stents (DES). During the ticagrelor period (TP, May 2014-August 2015) there were more major bleedings than during the clopidogrel period (CP, December 2012-April 2014).. To evaluate whether the excess of major bleedings during TP may be limited to high bleeding risk (HBR) patients, we performed an explorative analysis of all 2062 CHANGE DAPT participants, of whom 547(26.5%) were classified as HBR (CP, n = 245; TP, n = 302). In HBR and non-HBR patients, we assessed the impact of CP versus TP on propensity score-adjusted rates of major bleeding and a pre-defined ischemic endpoint (composite of cardiac death, myocardial infarction, or stroke) at 1-year follow-up. Among HBR patients, the rate of major bleeding was significantly higher during TP (1.7% vs. 5.0%; HR. Among consecutive ACS patients, the increased risk of major bleeding during ticagrelor-based DAPT was limited to HBR patients. In both HBR and non-HBR patients, ticagrelor-based DAPT did not reduce ischemic outcomes following treatment with contemporary DES implantation.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Clopidogrel; Drug-Eluting Stents; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Ticagrelor

The safety and efficacy of ticagrelor in patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remain uncertain.. The primary objective of the TicagRElor in pAtients with ST elevation myocardial infarction treated with Thrombolysis (TREAT) trial is to evaluate the short-term safety of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy. Key secondary objectives are to assess the safety and efficacy of ticagrelor compared with clopidogrel at 12-months.. The TREAT trial is a multicenter, randomized, phase III, Prospective randomized open blinded end-point (PROBE) study that enrolled 3,799 patients in 152 sites from 10 countries. Following administration of fibrinolytic therapy patients were randomized to a loading dose of ticagrelor 180 mg or clopidogrel 300 mg followed by a maintenance dose of ticagrelor 90 mg twice daily or clopidogrel 75 mg/day for 12-months. The primary outcome is the rate of TIMI major bleeding at 30-days and will be assessed for non-inferiority using an intention-to-treat analysis. Co-treatments include aspirin and anticoagulants. Other evidence based therapies are also recommended. Secondary efficacy outcome include a composite of death from vascular causes, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack or other arterial thrombotic event. All-cause mortality as well as individual components of the combined efficacy endpoint will also be ascertained.. TREAT is an international randomized controlled trial comparing ticagrelor with clopidogrel in STEMI patients treated with fibrinolytic therapy. The results of this trial will inform clinical practice and international guidelines.

Topics: Adult; Aged; Anticoagulants; Clopidogrel; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Intention to Treat Analysis; Male; Middle Aged; Prospective Studies; Purinergic P2Y Receptor Antagonists; Research Design; Single-Blind Method; ST Elevation Myocardial Infarction; Ticagrelor

Although switching between ticagrelor and clopidogrel is common in clinical practice, the efficacy and safety of this de-escalation remain controversial.. We assessed the occurrences, reasons, and outcomes of switching from ticagrelor to clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing successful primary percutaneous coronary intervention (PCI).. A total of 653 patients with STEMI were randomly assigned to receive loading dose of ticagrelor or clopidogrel before PCI and then received maintenance dose, respectively, for 12 months follow-up. The primary outcome was major adverse cardiac events (MACE), including cardiovascular death, nonfatal myocardial infarction, and stroke. The secondary outcome included unexpected rehospitalization for angina, coronary revascularization, and stent thrombosis. The safety outcome was bleeding described by the Bleeding Academic Research Consortium (BARC) criteria.. A total of 602 participants completed the study. The rate of switching from ticagrelor to clopidogrel was 48.6% and the main reason was financial burden. The rate of secondary ischemic events in the de-escalation group was higher than that in the ticagrelor group (15.1% vs 5.6%, P = 0.008), but lower than that in the clopidogrel group (15.1% vs 24.6%, P = 0.03), while there were no significant differences in MACE among the three groups (P = 0.16). De-escalation, ticagrelor, and clopidogrel did not cause significant differences in the rates of major bleeding among the three groups (BARC ≥ 2, P = 0.34).. Switching from ticagrelor to clopidogrel is very common in patients with STEMI in China. De-escalation might be safe but associated with high risk of ischemic events as compared to ticagrelor.

Topics: Aged; China; Clopidogrel; Coronary Thrombosis; Drug Costs; Drug Substitution; Female; Hemorrhage; Humans; Male; Middle Aged; Patient Readmission; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Recurrence; Risk Factors; ST Elevation Myocardial Infarction; Stroke; Ticagrelor; Time Factors; Treatment Outcome

 Ticagrelor is an anti-platelet agent that is indicated for prevention of thrombosis after acute coronary syndrome or intra-coronary artery stent implantation, but it increases the risk of bleeding. Platelet transfusion has the potential to treat or prevent bleeding in patients taking ticagrelor, but the optimal quantity of platelets and timing of administration have not been fully defined..  Ten healthy subjects took ticagrelor in combination with acetylsalicylic acid for 5 days, and had blood collected prior to treatment and at 2, 10, 24, 48, 72 and 96 hours after the last doses. The potential of platelet transfusion to prevent or reverse bleeding was evaluated by mixing subject and donor platelet-rich plasma in vitro in nine different proportions, and measuring adenosine diphosphate-mediated aggregation by light transmission aggregometry. Spontaneous offset of the anti-aggregant effect of ticagrelor occurred gradually and was complete at 72 hours after the last dose. The addition of donor platelets enhanced the recovery. The addition of the equivalent of six apheresis platelet units produced a 50% relative reversal at 10 hours, and > 90% reversal at 24 hours..  Donor platelets enhance reversal of the anti-aggregant effect of ticagrelor in vitro. Donor platelets given in clinically relevant amounts partially reversed ticagrelor at 10 hours after the last dose, and almost fully reversed ticagrelor at 24 hours. The results inform on the potential to reverse ticagrelor in patients who develop bleeding or require emergency surgery.

Topics: Acute Coronary Syndrome; Adenosine Diphosphate; Adult; Blood Platelets; Cells, Cultured; Female; Healthy Volunteers; Hemorrhage; Humans; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Transfusion; Platelet-Rich Plasma; Risk; Thrombosis; Ticagrelor; Young Adult

Dual antiplatelet therapy (DAPT), aspirin plus a P2Y12 inhibitor, is the standard antithrombotic treatment following acute coronary syndromes. The factor Xa inhibitor rivaroxaban reduced mortality and ischaemic events when added to DAPT, but caused increased bleeding. The safety of a dual pathway antithrombotic therapy approach combining low-dose rivaroxaban (in place of aspirin) with a P2Y12 inhibitor has not been assesssed in acute coronary syndromes. We aimed to assess rivaroxaban 2·5 mg twice daily versus aspirin 100 mg daily, in addition to clopidogrel or ticagrelor (chosen at investigator discretion before randomisation), for patients with acute coronary syndromes started within 10 days after presentation and continued for 6-12 months.. In this double-blind, multicentre, randomised trial (GEMINI-ACS-1) done at 371 clinical centres in 21 countries, eligible patients were older than 18 years with unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) or ST segment elevation myocardial infarction (STEMI), with positive cardiac biomarkers and either ischaemic electrocardiographic changes or an atherosclerotic culprit lesion identified during angiography. Participants were randomly assigned (1:1) within 10 days after admission for the index acute coronary syndromes event to either aspirin or rivaroxaban based on a computer-generated randomisation schedule. Randomisation was balanced by using randomly permuted blocks with size of four and was stratified based on the background P2Y12 inhibitor (clopidogrel or ticagrelor) intended to be used at the time of randomisation. Investigators and patients were masked to treatment assignment. Patients received a minimum of 180 days of double-blind treatment with rivaroxaban 2·5 mg twice daily or aspirin 100 mg daily. The choice of clopidogrel or ticagrelor during trial conduct was not randomised and was based on investigator preference. The primary endpoint was thrombolysis in myocardial infarction (TIMI) clinically significant bleeding not related to coronary artery bypass grafting (CABG; major, minor, or requiring medical attention) up to day 390. Primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02293395.. Between April 22, 2015, and Oct 14, 2016, 3037 patients with acute coronary syndromes were randomly assigned; 1518 to receive aspirin and 1519 to receive rivaroxaban. 1704 patients (56%) were in the ticagrelor and 1333 (44%) in the clopidogrel strata. Median duration of treatment was 291 days (IQR 239-354). TIMI non-CABG clinically significant bleeding was similar with rivaroxaban versus aspirin therapy (total 154 patients [5%]; 80 participants [5%] of 1519 vs 74 participants [5%] of 1518; HR 1·09 [95% CI 0·80-1·50]; p=0·5840).. A dual pathway antithrombotic therapy approach combining low-dose rivaroxaban with a P2Y12 inhibitor for the treatment of patients with acute coronary syndromes had similar risk of clinically significant bleeding as aspirin and a P2Y12 inhibitor. A larger, adequately powered trial would be required to definitively assess the efficacy and safety of this approach.. Janssen Research & Development and Bayer AG.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aspirin; Clopidogrel; Coronary Angiography; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Rivaroxaban; Thrombolytic Therapy; Ticagrelor; Ticlopidine; Treatment Outcome

Growth differentiation factor-15 (GDF-15) is related to major bleeding when measured at initial presentation in patients with acute coronary syndromes (ACSs) treated with dual antiplatelet therapy. It is unknown whether follow-up measurements provide additional information. The objective of this study was to investigate whether GDF-15 measured 1 month after an ACS provides additional information beyond the baseline levels with regard to the risk of major bleeding.. GDF-15 was measured at baseline and at 1 month after an ACS in 4049 patients included in the PLATelet inhibition and patient Outcomes (PLATO) trial. The association between 1-month GDF-15 level and non-coronary artery bypass grafting surgery-related major bleeding was assessed by a multivariable Cox model, adjusting for baseline GDF-15, age, anemia, impaired renal function, history of gastrointestinal bleeding, and sex. Elevated GDF-15 (>1800 ng/L) at 1 month was associated with an increased risk of non-coronary artery bypass grafting-related major bleeding (3.9% versus 1.2%; hazard ratio, 3.38; 95% CI, 1.89-6.06), independent of baseline GDF-15. Patients who had elevated GDF-15 levels at baseline and subsequent nonelevated GDF-15 at 1 month had a similar risk as patients who had nonelevated levels at both measurements.. GDF-15 at 1 month after an ACS is related to the risk of bleeding during DAPT and provides additional information on the bleeding risk beyond baseline GDF-15 levels. GDF-15 levels may therefore be useful as part of decision support concerning long-term antithrombotic treatment in patients post-ACS.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aspirin; Biomarkers; Clopidogrel; Double-Blind Method; Drug Therapy, Combination; Female; Growth Differentiation Factor 15; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Platelet Aggregation Inhibitors; Predictive Value of Tests; Proportional Hazards Models; Risk Assessment; Risk Factors; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome; Up-Regulation

Newer P2Y12 blockers (prasugrel and ticagrelor) demonstrated significant ischaemic benefit over clopidogrel after acute coronary syndrome (ACS). However, both drugs are associated with an increase in bleeding complications. The objective of the present study was to evaluate the benefit of switching dual antiplatelet therapy (DAPT) from aspirin plus a newer P2Y12 blocker to aspirin plus clopidogrel 1 month after ACS.. We performed an open-label, monocentric, and randomized trial. From March 2014 to April 2016, patients admitted with ACS requiring coronary intervention, on aspirin and a newer P2Y12 blocker and without adverse event at 1 month, were assigned to switch to aspirin and clopidogrel (switched DAPT) or continuation of their drug regimen (unchanged DAPT). The primary outcome was a composite of cardiovascular death, urgent revascularization, stroke and bleeding as defined by the Bleeding Academic Research Consortium (BARC) classification ≥2 at 1 year post ACS. Six hundred and forty six patients were randomized and 645 analysed, corresponding to 322 patients in the switched DAPT and 323 in the unchanged DAPT group. The primary endpoint occurred in 43 (13.4%) patients in the switched DAPT group and in 85 (26.3%) patients in the unchanged DAPT (HR 95%CI 0.48 (0.34-0.68), P < 0.01). No significant differences were reported on ischaemic endpoints, while BARC ≥ 2 bleeding occurred in 13 (4.0%) patients in the switched DAPT and in 48 (14.9%) in the unchanged DAPT group (HR 95%CI 0.30 (0.18-0.50), P < 0.01).. A switched DAPT is superior to an unchanged DAPT strategy to prevent bleeding complications without increase in ischaemic events following ACS.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Clopidogrel; Drug Administration Schedule; Drug Combinations; Drug Substitution; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Medication Adherence; Middle Aged; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Tablets; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

This study aimed to investigate the efficacy and safety of dual and triple antiplatelet therapy (DAPT and TAPT) in patients with diabetes and acute ST segment elevation myocardial infarction (D-STEMI), who had undergone primary percutaneous coronary intervention (PCI).. We designed a phase IV, single-centre, randomised, double-blind, placebo-controlled study. The D-STEMI patients (n = 258) were randomly divided into three groups. Control group A (85 patients), was treated with aspirin and clopidogrel; group B (87 patients) received aspirin, clopidogrel, and tirofiban; and group C (86 patients) were treated with aspirin, ticagrelor, and tirofiban. Patients in all three groups received oral DAPT, and patients in groups B and C received intravenous tirofiban when primary PCI was performed.. Compared to the findings in group A, the post-PCI Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow in groups B and C increased significantly (TIMI grade 3 in groups A, B, C: 74%, 91%, and 98%, respectively; TIMI myocardial perfusion grade [TMPG] grade 3 in groups A, B, C: 59%, 86%, and 97%, respectively), and the incidence of major adverse cardiac events (MACE) decreased significantly (p < 0.05). Compared to the findings in group B, the rate of TMPG 3 in group C was significantly higher (p < 0.05) and the incidence of MACE was significantly lower (p < 0.05). Patients in group B exhibited minor bleeding; however, the incidence of mild to moderate bleeding in group C increased significantly (p < 0.05).. TAPT effectively improved the TIMI blood flow and TMPG and reduced the occurrence of MACE. Ticagrelor was more effective than clopidogrel in TAPT; however, when using the combination of aspirin, ticagrelor, and tirofiban, close monitoring is required for possible bleeding complications.

Topics: Adenosine; Aged; Aspirin; Clopidogrel; Diabetic Cardiomyopathies; Double-Blind Method; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Patient Safety; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Ticagrelor; Ticlopidine; Tirofiban; Treatment Outcome; Tyrosine

Triple antithrombotic therapy with warfarin plus two antiplatelet agents is the standard of care after percutaneous coronary intervention (PCI) for patients with atrial fibrillation, but this therapy is associated with a high risk of bleeding.. In this multicenter trial, we randomly assigned 2725 patients with atrial fibrillation who had undergone PCI to triple therapy with warfarin plus a P2Y. The incidence of the primary end point was 15.4% in the 110-mg dual-therapy group as compared with 26.9% in the triple-therapy group (hazard ratio, 0.52; 95% confidence interval [CI], 0.42 to 0.63; P<0.001 for noninferiority; P<0.001 for superiority) and 20.2% in the 150-mg dual-therapy group as compared with 25.7% in the corresponding triple-therapy group, which did not include elderly patients outside the United States (hazard ratio, 0.72; 95% CI, 0.58 to 0.88; P<0.001 for noninferiority). The incidence of the composite efficacy end point was 13.7% in the two dual-therapy groups combined as compared with 13.4% in the triple-therapy group (hazard ratio, 1.04; 95% CI, 0.84 to 1.29; P=0.005 for noninferiority). The rate of serious adverse events did not differ significantly among the groups.. Among patients with atrial fibrillation who had undergone PCI, the risk of bleeding was lower among those who received dual therapy with dabigatran and a P2Y

Topics: Adenosine; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Dabigatran; Drug Therapy, Combination; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk; Ticagrelor; Ticlopidine; Warfarin

To evaluate gender differences in outcomes in patents with ST-segment elevation myocardial infarction (STEMI) planned for primary percutaneous coronary intervention (PPCI).. A prespecified gender analysis of the multicentre, randomised, double-blind Administration of Ticagrelor in the catheterisation Laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery.. Between September 2011 and October 2013, 1862 patients with STEMI and symptom duration <6 hours were included.. Patients were assigned to prehospital versus in-hospital administration of 180 mg ticagrelor.. The main objective was to study the association between gender and primary and secondary outcomes of the main study with a focus on the clinical efficacy and safety outcomes.. the proportion of patients who did not have 70% resolution of ST-segment elevation and did not meet the criteria for Thrombolysis In Myocardial Infarction (TIMI) flow 3 at initial angiography. Secondary outcome: the composite of death, MI, stent thrombosis, stroke or urgent revascularisation and major or minor bleeding at 30 days.. Women were older, had higher TIMI risk score, longer prehospital delays and better TIMI flow in the infarct-related artery. Women had a threefold higher risk for all-cause mortality compared with men (5.7% vs 1.9%, HR 3.13, 95% CI 1.78 to 5.51). After adjustment, the difference was attenuated but remained statistically significant (HR 2.08, 95% CI 1.03 to 4.20). The incidence of major bleeding events was twofold to threefold higher in women compared with men. In the multivariable model, female gender was not an independent predictor of bleeding (Platelet Inhibition and Patient Outcomes major HR 1.45, 95% CI 0.73 to 2.86, TIMI major HR 1.28, 95% CI 0.47 to 3.48, Bleeding Academic Research Consortium type 3-5 HR 1.45, 95% CI 0.72 to 2.91). There was no interaction between gender and efficacy or safety of randomised treatment.. In patients with STEMI planned for PPCI and treated with modern antiplatelet therapy, female gender was an independent predictor of short-term mortality. In contrast, the higher incidence of bleeding complications in women could mainly be explained by older age and clustering of comorbidities.. NCT01347580;Post-results.

Topics: Adenosine; Aged; Aged, 80 and over; Ambulances; Catheterization; Cause of Death; Coronary Vessels; Double-Blind Method; Emergency Medical Services; Female; Hemorrhage; Humans; International Cooperation; Male; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Purinergic P2Y Receptor Antagonists; Sex Factors; ST Elevation Myocardial Infarction; Survival Analysis; Ticagrelor; Time-to-Treatment; Treatment Outcome

Dual antiplatelet therapy (DAPT) with aspirin (ASP) and a P2Y. To compare TIC with TIC + ASP, we have initiated a single centre, open-label randomised controlled trial (TEMPLATE study) in adults receiving DAPT following PCI with a sample size of 110 patients. Patients are invited to join the study when, as part of standard care, they are due to switch from DAPT (ASP + any P2Y. This is the first study to compare in detail the extent of platelet inhibition in patients who are receiving TIC compared with TIC + ASP. The study findings will complement larger-scale trials of the clinical efficacy and safety of TIC compared to TIC + ASP.. ISRCTN registry, identifier ISRCTN84335288 . Registered on 23 June 2014.

Topics: Adenosine; Aspirin; Clinical Protocols; Coronary Artery Disease; Drug Therapy, Combination; England; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Research Design; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

This study sought to evaluate the impact of initial platelet reactivity on the benefit of switched strategy.. TOPIC (Timing Of Platelet Inhibition after acute Coronary Syndrome) study suggested that switched dual antiplatelet therapy (DAPT) could improve net clinical benefit after acute coronary syndrome by preventing bleeding.. Acute coronary syndrome patients, 1 month after coronary stenting and event free, were randomly assigned to aspirin and clopidogrel (switched DAPT) or continuation of drug regimen (unchanged DAPT). All patients underwent platelet function testing at this time and were classified as low on-treatment platelet reactivity (LTPR) (platelet reactivity index vasodilator-stimulated phosphoprotein ≤20%) or non-LTPR (platelet reactivity index vasodilator-stimulated phosphoprotein >20%). The primary endpoint aimed to evaluate the impact of platelet reactivity on clinical outcomes and benefit of switched DAPT strategy.. A total of 645 patients were included, 305 (47%) of whom were classified as LTPR. LTPR patients were less often diabetic (p = 0.01), had lower body mass index (p < 0.01), and were more often on ticagrelor (p < 0.01). Patients defined as LTPR and randomized to unchanged DAPT were at the highest risk of primary endpoint occurrence (31%; p < 0.01). Conversely, in the switched arm, LTPR patients had no significant difference in primary outcome incidence compared with non-LTPR patients (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.40 to 1.49; p = 0.45). The switched strategy was associated with important reduction in primary endpoint incidence in LTPR patients (HR: 0.29; 95% CI: 0.17 to 0.51; p < 0.01) and only numerically lower incidence in non-LTPR patients (HR: 0.79; 95% CI: 0.46 to 1.35; p = 0.39).. Switched DAPT was superior regardless of initial platelet reactivity but the benefit was greater in LTPR patients. Indeed, the switched strategy was highly effective in this group, which had impaired prognosis with unchanged DAPT but similar prognosis after switching.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Biomarkers; Blood Platelets; Cell Adhesion Molecules; Clopidogrel; Drug Monitoring; Drug Resistance; Drug Substitution; Drug Therapy, Combination; Female; France; Hemorrhage; Humans; Male; Microfilament Proteins; Middle Aged; Percutaneous Coronary Intervention; Phosphoproteins; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Risk Factors; Stents; Ticagrelor; Time Factors; Treatment Outcome

Ticagrelor has been endorsed by guidelines as the P2Y

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aged, 80 and over; Blood Platelets; Clopidogrel; Cross-Over Studies; Drug Administration Schedule; Drug Substitution; Female; Hemorrhage; Humans; Male; Middle Aged; Ontario; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Factors; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

The relationships between drug exposure and the composite risk of cardiovascular (CV) death, myocardial infarction (MI), and stroke as well as the risk of TIMI major bleeding were estimated following long-term treatment with ticagrelor 60 or 90 mg twice daily in 20,942 patients with prior MI. These analyses support the primary reported efficacy and safety evaluations by showing that there were clear separations from placebo early in treatment with both doses, regardless of ticagrelor exposure, for both endpoints. In addition, the exposure-response analyses provided new insight into the contribution of individual exposure levels, rather than dose, as a predictor of events and accounted for differences in the baseline risk between patients. The predicted risks of CV death/MI/stroke were similar despite an increase in the median predicted ticagrelor average steady-state concentration from 606 nmol/L with ticagrelor 60 mg to 998 nmol/L with ticagrelor 90 mg (hazard ratios vs placebo of 0.83 and 0.81, respectively). The corresponding predicted risk of TIMI major bleeding slightly increased (hazard ratios vs placebo of 2.4 and 2.6, respectively). Apart from Japanese patients, showing a lower risk of CV death/MI/stroke, the response to ticagrelor was consistent across the study population, as supported by the combination of relatively flat exposure-response relationships in the studied exposure range, similar sensitivity to ticagrelor exposure, and small exposure differences. Consequently, the present analyses support the selection of the 60-mg dose for all demographic subgroups of patients studied.

Topics: Adenosine; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Double-Blind Method; Female; Hemorrhage; Humans; Male; Middle Aged; Models, Biological; Myocardial Infarction; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor

In the SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), ticagrelor was not superior to aspirin. Because of differences in patient demographics and stroke disease pattern in Asia, outcomes of ticagrelor versus aspirin were assessed among Asian patients in a prespecified exploratory analysis.. Baseline demographics, treatment effects, and safety of ticagrelor and aspirin were assessed among Asian patients. Differences in outcomes between groups were assessed using Cox proportional hazard model.. A total of 3858 (29.2%) SOCRATES participants were recruited in Asia. Among the Asian patients, the primary end point event occurred in 186 (9.6%) of the 1933 patients treated with ticagrelor, versus 224 (11.6%) of the 1925 patients treated with aspirin (hazard ratio, 0.81; 95% confidence interval, 0.67-0.99). The exploratory P value for treatment-by-region interaction was 0.27. The primary end point event rate in the Asian subgroup was numerically higher than that in the non-Asian group (10.6% versus 5.7%; nominal P<0.01). Among the Asian patients, the rate of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeding was similar in the ticagrelor group and the aspirin group (0.6% versus 0.8%; hazard ratio, 0.76; 95% confidence interval, 0.36-1.61).. The event rates were numerically higher in the Asian patients. Among the Asian patients with acute stroke or transient ischemic attacks, there was a trend toward a lower hazard ratio in reducing risk of the primary end point of stroke, myocardial infarction, or death in the ticagrelor group.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.

Topics: Adenosine; Aged; Anti-Inflammatory Agents, Non-Steroidal; Asian People; Aspirin; Cohort Studies; Double-Blind Method; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Middle Aged; Purinergic P2Y Receptor Antagonists; Stroke; Ticagrelor; Treatment Outcome

Peripheral artery disease is considered to be a manifestation of systemic atherosclerosis with associated adverse cardiovascular and limb events. Data from previous trials have suggested that patients receiving clopidogrel monotherapy had a lower risk of cardiovascular events than those receiving aspirin. We wanted to compare clopidogrel with ticagrelor, a potent antiplatelet agent, in patients with peripheral artery disease.. In this double-blind, event-driven trial, we randomly assigned 13,885 patients with symptomatic peripheral artery disease to receive monotherapy with ticagrelor (90 mg twice daily) or clopidogrel (75 mg once daily). Patients were eligible if they had an ankle-brachial index (ABI) of 0.80 or less or had undergone previous revascularization of the lower limbs. The primary efficacy end point was a composite of adjudicated cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. The median follow-up was 30 months.. The median age of the patients was 66 years, and 72% were men; 43% were enrolled on the basis of the ABI and 57% on the basis of previous revascularization. The mean baseline ABI in all patients was 0.71, 76.6% of the patients had claudication, and 4.6% had critical limb ischemia. The primary efficacy end point occurred in 751 of 6930 patients (10.8%) receiving ticagrelor and in 740 of 6955 (10.6%) receiving clopidogrel (hazard ratio, 1.02; 95% confidence interval [CI], 0.92 to 1.13; P=0.65). In each group, acute limb ischemia occurred in 1.7% of the patients (hazard ratio, 1.03; 95% CI, 0.79 to 1.33; P=0.85) and major bleeding in 1.6% (hazard ratio, 1.10; 95% CI, 0.84 to 1.43; P=0.49).. In patients with symptomatic peripheral artery disease, ticagrelor was not shown to be superior to clopidogrel for the reduction of cardiovascular events. Major bleeding occurred at similar rates among the patients in the two trial groups. (Funded by AstraZeneca; EUCLID ClinicalTrials.gov number, NCT01732822 .).

Topics: Adenosine; Aged; Cardiovascular Diseases; Clopidogrel; Double-Blind Method; Female; Hemorrhage; Humans; Intermittent Claudication; Ischemia; Kaplan-Meier Estimate; Leg; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine

We evaluated the relationship of renal function and ischaemic and bleeding risk as well as the efficacy and safety of ticagrelor in stable patients with prior myocardial infarction (MI).. Patients with a history of MI 1-3 years prior from PEGASUS-TIMI 54 were stratified based on estimated glomerular filtration rate (eGFR), with <60 mL/min/1.73 m(2) pre-specified for analysis of the effect of ticagrelor on the primary efficacy composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events, MACE) and the primary safety endpoint of TIMI major bleeding. Of 20 898 patients, those with eGFR <60 (N = 4849, 23.2%) had a greater risk of MACE at 3 years relative to those without, which remained significant after multivariable adjustment (hazard ratio, HRadj 1.54, 95% confidence interval, CI 1.27-1.85, P < 0.001). The relative risk reduction in MACE with ticagrelor was similar in those with eGFR <60 (ticagrelor pooled vs. placebo: HR 0.81; 95% CI 0.68-0.96) vs. ≥60 (HR 0.88; 95% CI 0.77-1.00, Pinteraction = 0.44). However, due to the greater absolute risk in the former group, the absolute risk reduction with ticagrelor was higher: 2.7 vs. 0.63%. Bleeding tended to occur more frequently in patients with renal dysfunction. The absolute increase in TIMI major bleeding with ticagrelor was similar in those with and without eGFR <60 (1.19 vs. 1.43%), whereas the excess of minor bleeding tended to be more pronounced (1.93 vs. 0.69%).. In patients with a history of MI, patients with renal dysfunction are at increased risk of MACE and consequently experience a particularly robust absolute risk reduction with long-term treatment with ticagrelor.

Topics: Adenosine; Aged; Coronary Artery Disease; Coronary Thrombosis; Drug Administration Schedule; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Renal Insufficiency, Chronic; Risk Factors; Ticagrelor; Treatment Outcome

Ticagrelor reduced major adverse cardiovascular event (MACE) by 15-16% in patients with prior myocardial infarction (MI) in PEGASUS-TIMI 54. We hypothesized that patients who recently discontinued P2Y12 inhibition, even years after MI, may be at particular risk of MACE and may derive particular benefit from continuation or reinitiation of therapy.. Patients in PEGASUS-TIMI 54 were categorized by time from last P2Y12 inhibitor (days: ≤30, >30-360, >360). The risk of MACE and the efficacy of ticagrelor were compared across categories. In the placebo arm, patients who more recently stopped P2Y12 inhibitor therapy had a greater number of risk factors but still had a higher risk of MACE after multivariable adjustment [≤30 days, hazard ratio (HR)adj 1.47, 95% confidence interval (CI) 1.12-1.93, P = 0.0051; 30 days-1 year, HRadj 1.28, 95% CI 0.98-1.67, P = 0.073] compared with those who stopped >1 year prior (P-trend = 0.0097). The benefit of ticagrelor depended on the time from last dose, with HRs (95% CI) for ticagrelor (pooled doses) vs. placebo of 0.73 (0.61-0.87), 0.86 (0.71-1.04), and 1.01 (0.80-1.27), respectively, by category (P-trend for interaction < 0.001). The benefit in those ≤30 days of stopping was similar regardless of time from MI (<2 years, HR 0.73, 95% CI 0.60-0.89 vs. ≥2 years, HR 0.71, 95% CI 0.50-1.00).. The benefit of ticagrelor for long-term secondary prevention in patients with prior MI and at least one additional risk factor appeared more marked in patients continuing on or re-starting after only a brief interruption of P2Y12 inhibition, when compared with patients who had proved themselves stable more than 2 years from their MI and off P2Y12 inhibitor therapy for more than a year. The increase in bleeding events with ticagrelor was similar regardless of this time interval. For clinicians considering a strategy of prolonged P2Y12 inhibitor therapy in high-risk patients, these data suggest greater benefit in the continuation of such therapy without interruption after MI, rather than re-initiating such therapy in patients who have remained stable for an extended period. Future analyses may help to clarify further the profile of post-MI patients most likely to benefit from uninterrupted dual antiplatelet therapy.. http://www.clinicaltrials.gov NCT01225562.

Topics: Adenosine; Aged; Drug Administration Schedule; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Purinergic P2Y Receptor Antagonists; Risk Factors; Secondary Prevention; Ticagrelor; Treatment Outcome

The GLOBAL LEADERS trial is a superiority study in patients undergoing percutaneous coronary intervention, with a uniform use of Biolimus A9-eluting stents (BES) and bivalirudin. GLOBAL LEADERS was designed to assess whether a 24-month antithrombotic regimen with ticagrelor and one month of acetylsalicylic acid (ASA), compared to conventional dual antiplatelet therapy (DAPT), improves outcomes.. Patients (n >16,000) are randomised (1:1 ratio) to ticagrelor 90 mg twice daily for 24 months plus ASA ≤100 mg for one month versus DAPT with either ticagrelor (acute coronary syndrome) or clopidogrel (stable coronary artery disease) for 12 months plus ASA ≤100 mg for 24 months. The primary outcome is a composite of all-cause mortality or non-fatal, new Q-wave myocardial infarction at 24 months. The key safety endpoint is investigator-reported class 3 or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) definitions. Sensitivity analysis will be carried out to explore potential differences in outcome across geographic regions and according to specific angiographic and clinical risk estimates.. The GLOBAL LEADERS trial aims to assess the role of ticagrelor as a single antiplatelet agent after a short course of DAPT for the long-term prevention of cardiac adverse events, across a wide spectrum of patients, following BES implantation.

Topics: Acute Coronary Syndrome; Adenosine; Adolescent; Adult; Aged; Aged, 80 and over; Aspirin; Drug Combinations; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Sirolimus; Ticagrelor; Time; Treatment Outcome; Young Adult

Ticagrelor was shown to reduce mortality in patients who underwent coronary artery bypass grafting (CABG), but its effect on graft patency is unknown.. We performed a prospective, randomised, double-blind, placebo-controlled trial, comparing ticagrelor 90 mg twice daily versus placebo for 3 months added to aspirin 81 mg/day, following isolated CABG. Aspirin was started within 12 h, and study medication within 72 h after CABG. Primary outcome was graft occlusion on CT angiography (CTA) performed 3 months post CABG. Patients were followed to 12 months for death, myocardial infarction, stroke, repeat revascularisation and bleeding.. The study was terminated prematurely after randomising 70 patients between September 2011 and August 2014 because of slow recruitment. CTA was performed in 56 patients who completed >1 month of study drug. Graft occlusion occurred in 7/25 (28.0%) patients on ticagrelor and 17/31 (48.3%) on placebo, p=0.044. Of 207 analysable grafts, graft occlusion occurred in 9/87 (10.3%) with ticagrelor and 22/120 (18.3%) with placebo, p=0.112. Graft occlusion or stenosis ≥50% occurred in 10/87 (11.5%) ticagrelor vs 32/120 (26.7%) placebo, p=0.007. There was no major bleeding, but minor bleeding was higher with ticagrelor (31.4% vs 2.9%, p=0.003). In univariate analysis, ticagrelor use reduced graft occlusion (OR 0.32, 95% CI 0.10 to 0.97, p=0.047), which remained significant on multivariable analysis (OR 0.25, 95% CI 0.073 to 0.873, p=0.03).. Ticagrelor added to aspirin after CABG reduced the proportion of patients with graft occlusion, and was a significant univariate and multivariable predictor of graft occlusion. These results are hypothesis-generating and should be confirmed in larger studies.. NCT01373411: Results.

Topics: Adenosine; Aged; Aspirin; British Columbia; Chi-Square Distribution; Computed Tomography Angiography; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Double-Blind Method; Early Termination of Clinical Trials; Female; Graft Occlusion, Vascular; Hemorrhage; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; Vascular Patency

Ticagrelor improves the clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). However, few studies have directly compared the efficacy and safety of ticagrelor against clopidogrel, an oral, thienopyridine-class antiplatelet drug. This study compared the efficacy and safety of ticagrelor and clopidogrel in patients with STEMI undergoing PPCI.. We enrolled 400 patients with STEMI undergoing PPCI at the Zhujiang Hospital of Southern Medical University and the First Hospital of Qinhuangdao, China, between January 01, 2013 and April 30, 2015. All patients received 300 mg of aspirin and were randomized to receive one of the following treatments: (1) a loading dose of clopidogrel (600 mg) before PPCI followed by clopidogrel (75 mg once daily for 1 year) post PPCI or (2) a loading dose of ticagrelor (180 mg) before PPCI followed by ticagrelor (90 mg twice daily for 1 year) post PPCI. Some patients were treated by intracoronary bolus of a glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor [tirofiban (10 μg/kg) plus maintenance infusion (0.15 μg·kg·min) for 24-36 hours] in accordance with specified guidelines. The primary end points evaluated were major adverse cardiovascular and cerebrovascular event (MACCE) [defined as a composite of overall death, myocardial infarction (MI), unplanned revascularization, or stroke], stent thrombosis, and the composite end point of CV death, nonfatal MI, and stroke. The supplemental use of GPIIb/IIIa inhibitors in the clopidogrel and ticagrelor groups was monitored as another study end point, although the secondary safety end point evaluated was the incidence of bleeding events.. Compared with the clopidogrel-treated group, ticagrelor treatment significantly reduced the incidence of MACCE [5 vs. 14; odds ratio (OR), 0.341; 95% confidence interval (CI), 0.120-0.964; P = 0.034] and the composite end points of cardiovascular death, nonfatal MI, and stroke (4 vs. 13; OR, 0.294; 95% CI, 0.094-0.916; P = 0.026). Fewer patients in the ticagrelor group received GPIIb/IIIa inhibitors after PPCI compared with those in the clopidogrel group (10 vs. 21; OR, 0.449; 95% CI, 0.206-0.979; P = 0.040). However, there were no significant differences between the groups in the incidences of all-cause mortality, nonfatal MI, unplanned revascularization, stroke, stent thrombosis (P = 0.522, P = 0.246, P = 0.246, P = 0.217, P = 0.246, respectively), or bleeding events (10 vs. 7; OR, 1.451; 95% CI, 0.541-3.891; P = 0.457).. Among patients with STEMI undergoing PPCI, ticagrelor reduces the incidence of MACCE and the composite end point of cardiovascular death, nonfatal MI, and stroke compared with clopidogrel. Ticagrelor also reduces the need for GPIIb/IIIa inhibitors. However, no significant difference was observed in the risk of bleeding between the 2 groups.

Topics: Adenosine; Aged; Chi-Square Distribution; China; Clopidogrel; Coronary Thrombosis; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recurrence; Risk Factors; ST Elevation Myocardial Infarction; Stroke; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Patients with diabetes appear to be at elevated risk of atherothrombotic events.. The purpose of this study was to determine the effect of antiplatelet therapy with ticagrelor on recurrent ischemic events in patients with diabetes and prior myocardial infarction (MI).. We examined the subgroups of patients with diabetes (n = 6,806) and without diabetes (n = 14,355) from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54), in which 21,162 patients with a history of MI 1 to 3 years prior and with additional risk factors were randomized to ticagrelor (90 or 60 mg twice daily) or placebo. Patients were followed for a median of 33 months. The primary efficacy endpoint was major adverse cardiovascular events (MACE) (cardiovascular death, MI, stroke) and the primary safety endpoint was TIMI (Thrombolysis In Myocardial Infarction) major bleeding.. The relative risk reduction in MACE with ticagrelor was consistent for the pooled doses versus placebo in patients with diabetes (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.72 to 0.99; p = 0.035) and without diabetes (HR: 0.84; 95% CI: 0.74 to 0.96; p = 0.013; p interaction = 0.99). As patients with diabetes were at higher risk of MACE, the absolute risk reduction tended to be greater in patients with versus without diabetes (1.5% vs. 1.1%, with corresponding 3-year number needed to treat of 67 vs. 91). In patients with diabetes requiring pharmacological therapy (n = 5,960), the absolute risk reduction was 1.9% with a 3-year number needed to treat of 53. Additionally, in patients with diabetes, ticagrelor reduced cardiovascular death by 22% and coronary heart disease death by 34%. Similar to patients without diabetes, there was increased TIMI major bleeding in patients with diabetes (HR: 2.56; 95% CI: 1.52 to 4.33; p = 0.0004).. In patients with diabetes with prior MI, adding ticagrelor to aspirin significantly reduces the risk of recurrent ischemic events, including cardiovascular and coronary heart disease death. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).

Topics: Adenosine; Aged; Coronary Disease; Diabetes Mellitus; Dose-Response Relationship, Drug; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Stroke; Ticagrelor

Peripheral artery disease (PAD) is associated with heightened ischemic and bleeding risk in patients with prior myocardial infarction (MI).. This study evaluated the efficacy and safety of ticagrelor on major cardiovascular (CV) events and major adverse limb events in patients with PAD and a prior MI.. PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54) randomized 21,162 patients with prior MI (1 to 3 years) to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo, all on a background of low-dose aspirin. History of PAD was obtained at baseline. Occurrences of major adverse cardiovascular events (MACE) (defined as CV death, MI, or stroke) and major adverse limb events (MALE) (defined as acute limb ischemia or peripheral revascularization for ischemia) were recorded in follow-up.. A total of 1,143 patients (5%) had known PAD. In the placebo arm, those with PAD (n = 404) had higher rates of MACE at 3 years than those without (n = 6,663; 19.3% vs. 8.4%; p < 0.001), which persisted after adjusting for baseline differences (adjusted hazard ratio: 1.60; 95% confidence interval: 1.20 to 2.13; p = 0.0013), and higher rates of acute limb ischemia (1.0% vs. 0.1%) and peripheral revascularization procedures (9.15% vs. 0.46%). Whereas the relative risk reduction in MACE with ticagrelor was consistent, regardless of PAD, patients with PAD had a greater absolute risk reduction of 4.1% (number needed to treat: 25) due to their higher absolute risk. The absolute excess of TIMI major bleeding was 0.12% (number needed to harm: 834). The 60-mg dose had particularly favorable outcomes for CV and all-cause mortality. Ticagrelor (pooled doses) reduced the risk of MALE (hazard ratio: 0.65; 95% confidence interval: 0.44 to 0.95; p = 0.026).. Among stable patients with prior MI, those with concomitant PAD have heightened ischemic risk. In these patients, ticagrelor reduced MACE, with a large absolute risk reduction, and MALE. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS-TIMI 54]; NCT01225562).

Topics: Adenosine; Aged; Aspirin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Hemorrhage; Humans; Ischemia; Lower Extremity; Male; Middle Aged; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Stroke; Ticagrelor; Vascular Grafting

Long-awaiting PHILO trial, conducted in 2011-2012 has been submitted and published late in 2015. In contrast to overall PLATO results, but similar to PLATO-US cohort, PHILO revealed numerical inferiority of ticagrelor with regard to death, myocardial infarction, stroke, and bleeding over clopidogrel. Hence, we comprehend the PHILO results in light of the PLATO-US evidence. To assess the PHILO (n=801) outcomes, applied statistics, and trial conduct, matching them with the PLATO-US (n=1413) patients. The Asian, predominantly Japanese ticagrelor patients had worsened outcomes even when compared to the negative American cohort with regard to death (OR=1.44 (PHILO) vs. 1.17 (PLATO-US); myocardial infarction (OR=1.63 vs. 1.38); and composite primary endpoint (OR=1.60 vs. 1.27); but not for stroke (OR=1.51 vs. 1.75). Moreover, in contrast to the trend in PLATO-US (OR=1.11; CI=0.84-1.48, p=0.46), PHILO revealed significant excess of PLATO-defined composite of major and minor bleeding events (OR=1.83; CI=1.27-2.63,p=0.0014). PLATO-defined "net clinical benefit" in PHILO was also significantly (OR=1.61; CI=1.11-2.34, p=0.0145) inferior for ticagrelor. The "number needed to harm" suggests that for every 29 PHILO patients treated for 12months with ticagrelor instead of clopidogrel, one will suffer an additional major bleeding event. Finally, unexplained premature closure of PHILO just after 200-210days mean drug exposure, and short 240days mean follow-up seems deliberate and concerning with regard to unblinding. Aside from some information censoring, early trial closure, and creative statistics, Asian ticagrelor patients did consistently worse in PHILO, than even in the negative PLATO-US cohort. Especially alarming is a significant bleeding inferiority justifying a necessity for a separate outcome-driven low-dose ticagrelor trial in Asian post-PCI patients. This strategy was successfully implemented with the low-dose prasugrel in Japan. Regulatory authorities in Asia may consider conducting an independent review of PHILO dataset to ensure adequate ticagrelor safety.

Topics: Acute Coronary Syndrome; Adenosine; Asian People; Aspirin; Black People; Clopidogrel; Hemorrhage; Humans; Japan; Ticagrelor; Ticlopidine; Treatment Outcome; United States; White People

Ticagrelor may be a more effective antiplatelet therapy than aspirin for the prevention of recurrent stroke and cardiovascular events in patients with acute cerebral ischemia.. We conducted an international double-blind, controlled trial in 674 centers in 33 countries, in which 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack who had not received intravenous or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive either ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2 through 90). The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.. During the 90 days of treatment, a primary end-point event occurred in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P=0.07). Ischemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%.. In our trial involving patients with acute ischemic stroke or transient ischemic attack, ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01994720.).

Topics: Adenosine; Aged; Aspirin; Double-Blind Method; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Kaplan-Meier Estimate; Male; Middle Aged; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Stroke; Ticagrelor

Ticagrelor reduced cardiovascular events compared with clopidogrel in PLATO without increasing overall major bleeding. We evaluated whether the use of glycoprotein IIb/IIIa inhibitor (GPI) impacts the relative efficacy and safety of ticagrelor compared with clopidogrel.. PLATO randomized 18,624 subjects with acute coronary syndrome to ticagrelor versus clopidogrel. The primary efficacy end point was cardiovascular death/myocardial infarction/stroke, and the primary safety end point was major bleeding. The use of GPI was at the physician's discretion and open-label. We evaluated outcomes at 30 days stratified by GPI use in the subgroup of 9,983 patients who underwent percutaneous coronary intervention (PCI) within 72 hours.. A total of 4,020 (40%) received a GPI. Those receiving a GPI were more likely to be younger, be male, and undergo multivessel PCI. There was no interaction between treatment and GPI use for the primary efficacy and safety end points. Patients treated without GPI had a lower rate of definite stent thrombosis and higher rate of minor/major bleeding with ticagrelor compared with clopidogrel (P < .05), whereas there was no such difference with GPI (P interaction < .05).. In patients with acute coronary syndrome undergoing early PCI, the efficacy and safety of ticagrelor as compared with clopidogrel were not modified by GPI use according to the primary efficacy and safety end point of the trial, although there were indications of greater benefit on definite stent thrombosis and more major or minor bleeding with ticagrelor in patients without (vs with) GPI treatment.

Topics: Abciximab; Acute Coronary Syndrome; Adenosine; Aged; Antibodies, Monoclonal; Aspirin; Cardiovascular Diseases; Clopidogrel; Drug Therapy, Combination; Drug-Eluting Stents; Eptifibatide; Female; Graft Occlusion, Vascular; Hemorrhage; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Myocardial Infarction; Peptides; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Purinergic P2Y Receptor Antagonists; Stroke; Thrombosis; Ticagrelor; Ticlopidine; Tirofiban; Tyrosine

To compare three glycoprotein IIb/IIIa receptor antagonists (GPIs) in terms of platelet inhibition and major adverse cardiac events (MACEs), and assess the rate of bleeding and MACEs between GPIs and coadministered P2Y12 agents.. Eighty-three acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) with planned GPI use were randomized to receive high-dose bolus tirofiban, double-bolus eptifibatide, or abciximab followed by a 12-hour infusion. Glycoprotein IIb/IIIa platelet receptor inhibition was measured at baseline and at 10 minutes, 1 hour, and 24 hours postbolus dose. Major adverse cardiac events and bleeding complications at 30 days were documented. The incidence of MACEs and bleeding in patients receiving ticagrelor or prasugrel were compared to those given clopidogrel.. There were no statistically significant differences in platelet inhibition between GPIs at 10 minutes (P=.085) and 1 hour (P=.337). At 24 hours, abciximab achieved statistically significantly higher median [interquartile range] platelet inhibition (75 [65-88]%) compared to tirofiban (28 [3-56]%; P<.0001) and eptifibatide (44 [31-63]%; P=.007). There were no differences in bleeding or MACEs depending on GPI or P2Y12 inhibitor administered.. Glycoprotein receptor inhibitors achieve similar levels of platelet inhibition at 10 minutes and 1 hour; however, abciximab maintains this benefit 24 hours after bolus dose. We did not witness an increased rate of bleeding in patients given new potent P2Y12 inhibitors and a GPI in the modern era.

Topics: Abciximab; Acute Coronary Syndrome; Adenosine; Aged; Antibodies, Monoclonal; Blood Platelets; Clopidogrel; Drug Therapy, Combination; Eptifibatide; Female; Hemorrhage; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; New South Wales; Peptides; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Factors; Ticagrelor; Ticlopidine; Time Factors; Tirofiban; Treatment Outcome; Tyrosine

In the PEGASUS-TIMI 54 trial, treatment with ticagrelor reduced the incidence of cardiovascular death, myocardial infarction, or stroke by 15% to 16% among stable patients compared with placebo. However, more patients prematurely discontinued treatment with ticagrelor than with placebo.. To investigate the reasons and timing of discontinuation of treatment with ticagrelor among stable patients prior myocardial infarction.. In the PEGASUS-TIMI 54 trial, 21 162 stable outpatients with prior myocardial infarction were randomly assigned to 90 mg of ticagrelor twice daily, 60 mg of ticagrelor twice daily, or placebo, with all of the patients receiving a low dose of aspirin. These participants were followed up for a median of 33 months (study start date: October 2010; completion date: December 2014). Discontinuation of treatment was evaluated by treatment arm, cause, and timing. This analysis was initiated in May 2015.. Discontinuation of treatment.. Over 33 months, 32%, 29%, and 21% of patients receiving 90 mg of ticagrelor, 60 mg of ticagrelor, and placebo, respectively, discontinued treatment (P < .001). Discontinuation of treatment due to an adverse event occurred in 19%, 16%, and 9% of patients, respectively (P < .001). The most frequent adverse events leading to discontinuation of treatment were bleeding (with Kaplan-Meier event rates of 7.8%, 6.2%, and 1.5% of patients, respectively; P < .001) and dyspnea (6.5%, 4.6%, and 0.8% of patients, respectively; P < .001). Eighty-six percent of bleeding events that led to the discontinuation of treatment with ticagrelor were nonmajor, and 86% of adverse events due to dyspnea that led to discontinuation of treatment with ticagrelor were mild or moderate in severity. The discontinuation rates are annualized for patients who received 90 mg of ticagrelor twice daily (hazard ratio [HR], 2.00 [95% CI, 1.84-2.16] for the first year; HR, 1.12 [95% CI, 1.00-1.26] for the second and third years) and patients who received 60 mg of ticagrelor twice daily (HR, 1.59 [95% CI, 1.46-1.73] for the first year; HR, 1.18 [95% CI, 1.06-1.32] for the second and third years) compared with patients who received placebo.. When initiated among stable patients with prior myocardial infarction, discontinuation of treatment with ticagrelor was driven primarily by nonserious adverse events occurring primarily early after randomization. For patients completing 1 year of treatment, the subsequent discontinuation rate was low. These data demonstrate how adverse events considered "nonserious" by traditional trial criteria may have an effect on quality of life and, thus, may precipitate the discontinuation of treatments and underscore the need for patient education and counseling on the timing and nature of adverse effects with the aim of improving adherence when appropriate.. clinicaltrials.gov Identifier: NCT01225562.

Topics: Adenosine; Dyspnea; Hemorrhage; Humans; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Quality of Life; Secondary Prevention; Stroke; Ticagrelor

The optimal duration of dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients treated with drug eluting stents (DES) is still under debate. Recent meta-analyses on ≤6months versus 12months DAPT suggest that bleeding rates can be reduced, without a higher rate of thrombotic complications. In particular, the COMBO dual therapy stent, being associated with early re-endothelialization, may allow for a reduction of the duration of DAPT without increasing the thrombotic risk, while reducing the risk of bleeding complications.. The aim of the REDUCE trial is to demonstrate the non-inferiority of a combined efficacy and safety endpoint of a short-term 3months DAPT strategy as compared to standard 12-month DAPT strategy in ACS patients treated with the COMBO stent.. A prospective, multicenter, randomized study designed to enroll 1500 patients with ACS treated with the COMBO stent. Patients will be randomized before discharge in a 1:1 fashion to either 3 or 12months of DAPT. A clinical follow-up is scheduled at 3, 6, 12, and 24months. The primary endpoint is the time to event as defined by the occurrence of one of the following: all cause mortality, myocardial infarction, stent thrombosis, stroke, target vessel revascularization or bleeding (Bleeding Academic Research Council type II, III and V) within 12months. The study has recruited patients since July 2014, and the results are expected in 2017.. A reduction of the DAPT duration in ACS patients after PCI without affecting the thrombotic risk is an attractive option with regard to the associated bleeding risk. The REDUCE trial will be the first to investigate the efficacy and safety of a 3-month DAPT strategy compared to a 12-month DAPT strategy in an ACS only population treated with the COMBO stent.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Cause of Death; Clopidogrel; Coronary Artery Disease; Drug Therapy, Combination; Drug-Eluting Stents; Graft Occlusion, Vascular; Hemorrhage; Humans; Mortality; Myocardial Infarction; Myocardial Revascularization; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Stroke; Thrombosis; Ticagrelor; Ticlopidine; Time Factors

In the PEGASUS-TIMI 54 trial (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54), ticagrelor reduced the risk of major adverse cardiovascular events when added to low-dose aspirin in stable patients with prior myocardial infarction, resulting in the approval of ticagrelor 60 mg twice daily for long-term secondary prevention. We investigated the incidence of stroke, outcomes after stroke, and the efficacy of ticagrelor focusing on the approved 60 mg twice daily dose for reducing stroke in this population.. Patients were followed for a median of 33 months. Stroke events were adjudicated by a central committee. Data from similar trials were combined using meta-analysis.. Of 14 112 patients randomly assigned to placebo or ticagrelor 60 mg, 213 experienced a stroke; 85% of these strokes were ischemic. A total of 18% of strokes were fatal and another 15% led to either moderate or severe disability at 30 days. Ticagrelor significantly reduced the risk of stroke (hazard ratio, 0.75; 95% confidence interval, 0.57-0.98; P=0.034), driven by a reduction in ischemic stroke (hazard ratio, 0.76; 95% confidence interval, 0.56-1.02). Hemorrhagic stroke occurred in 9 patients on placebo and 8 patients on ticagrelor. A meta-analysis across 4 placebo-controlled trials of more intensive antiplatelet therapy in 44 816 patients with coronary disease confirmed a marked reduction in ischemic stroke (hazard ratio, 0.66; 95% confidence interval, 0.54-0.81; P=0.0001).. High-risk patients with prior myocardial infarction are at risk for stroke, approximately one-third of which are fatal or lead to moderate-to-severe disability. The addition of ticagrelor 60 mg twice daily significantly reduced this risk without an excess of hemorrhagic stroke but with more major bleeding. In high-risk patients with coronary disease, more intensive antiplatelet therapy should be considered not only to reduce the risk of coronary events, but also of stroke.. URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01225562.

Topics: Adenosine; Aged; Aspirin; Coronary Artery Disease; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk; Secondary Prevention; Stroke; Ticagrelor

Topics: Acute Coronary Syndrome; Adenosine; Aged; China; Clopidogrel; Cytochrome P-450 CYP2C19; Dose-Response Relationship, Drug; Drug Monitoring; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Long Term Adverse Effects; Male; Middle Aged; Percutaneous Coronary Intervention; Pharmacogenomic Testing; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; Treatment Outcome

Dual antiplatelet therapy (DAPT) is necessary to prevent thrombosis yet increases bleeding after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Antiplatelet monotherapy with a potent P2Y. TWILIGHT is a randomized, double-blind placebo-controlled trial evaluating the comparative efficacy and safety of antiplatelet monotherapy versus DAPT in up to 9000 high-risk patients undergoing PCI with DES. Upon enrollment after successful PCI, all patients will be treated with open label low-dose aspirin (81-100 mg daily) plus ticagrelor (90 mg twice daily) for 3 months. Event-free patients will then be randomized in a double-blind fashion to low-dose aspirin versus matching placebo with continuation of open-label ticagrelor for an additional 12 months. The primary hypothesis is that a strategy of ticagrelor monotherapy will be superior with respect to the primary endpoint of bleeding academic research consortium type 2, 3 or 5, while maintaining non-inferiority for ischemic events compared with ticagrelor plus ASA.. TWILIGHT is the largest study to date that is specifically designed and powered to demonstrate reductions in bleeding with ticagrelor monotherapy versus ticagrelor plus ASA beyond 3 months post-procedure in a high-risk PCI population treated with DES. The trial will provide novel insights with respect to the potential role of ticagrelor monotherapy as an alternative for long-term platelet inhibition in a broad population of patients undergoing PCI with DES.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aspirin; Coronary Restenosis; Double-Blind Method; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Adjustment; Ticagrelor; Treatment Outcome

To determine the effect of ticagrelor compared to clopidogrel in patients with peripheral artery disease (PAD) and acute coronary syndromes (ACS).. PLATO (n = 18,624) was a multicentre, double-blind, randomized trial in ACS, that showed a 16% reduction in cardiovascular death (CV-death), myocardial infarction (MI) and stroke with ticagrelor compared with clopidogrel, without significant increase in overall major bleeding. We performed a post-hoc analysis of cardiovascular and bleeding outcomes in PLATO according to reported PAD status at baseline. At one year, CV death, MI or stroke occurred in 19.3% of patients with PAD (n = 1144) compared to 10.2% in patients without PAD (p < 0.001). The Kaplan-Meier one year event rate for the primary endpoint of CV death, MI or stroke in PAD patients treated with ticagrelor as compared with clopidogrel, was 18% vs 20.6% (HR: 0.85 95% CI 0.64-1.11; for PAD status by treatment interaction, p = 0.99) and for death from any cause 8.7% vs 11.9%, (HR: 0.74 95% CI 0.50-1.08; interaction p = 0.73). PLATO-defined major bleeding event rates at one year were 14.8% for ticagrelor compared to 17.9% for clopidogrel, (HR: 0.81 95% CI 0.59-1.10; interaction p = 0.09).. PAD patients have a high rate of ischaemic and bleeding events post ACS. The reduction of CV death, MI or stroke with ticagrelor compared with clopidogrel in PAD patients was consistent with the overall trial result although it did not reach statistical significance. Overall major bleeding was similar between the therapies.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Double-Blind Method; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Proportional Hazards Models; Risk Factors; Stroke; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

We sought to describe the differential effect of bleeding events in acute coronary syndromes (ACS) on short- and long-term mortality according to their type and severity.. The PLATO trial randomised 18,624 ACS patients to clopidogrel or ticagrelor. Post-randomisation bleeding events were captured according to bleeding type (spontaneous or procedure-related), with PLATO, TIMI, and GUSTO definitions. The association of bleeding events with subsequent short-term (<30 days) and long-term (>30 days) all-cause mortality was assessed using time-dependent Cox proportional hazard models. A model was fitted to compare major and minor bleeding for mortality prediction. Of 18,624 patients, 2,189 (11.8%) had at least one PLATO major bleed (mean follow-up 272.2±123.5 days). Major bleeding was associated with higher short-term mortality (adjusted hazard ratio [HR] 9.28; 95% confidence interval [CI]: 7.50-11.48) but not with long-term mortality (adjusted HR 1.28; 95% CI: 0.93-1.75). Spontaneous bleeding was associated with short-term (adjusted HR 14.59; 95% CI: 11.14-19.11) and long-term (adjusted HR 3.38; 95% CI: 2.26-5.05) mortality. Procedure-related bleeding was associated with short-term mortality (adjusted HR 5.29; 95% CI: 4.06-6.87): CABG-related and non-coronary-procedure-related bleeding were associated with a higher short-term mortality, whereas PCI or angiography-related bleeding was not associated with either short- or long-term mortality. Similar results were obtained using the GUSTO and TIMI bleeding definitions.. Major bleeding is associated with high subsequent mortality in ACS. However, this association is much stronger in the first 30 days and is strongest for spontaneous (vs. procedure-related) bleeding.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Coronary Angiography; Coronary Artery Bypass; Double-Blind Method; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Predictive Value of Tests; Proportional Hazards Models; Risk Assessment; Risk Factors; Severity of Illness Index; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Long-term oral anticoagulant treatment is obligatory in patients with atrial fibrillation (AF, score of CHA₂DS₂VASc≥2). When these patients undergo percutaneous coronary intervention with a drug-eluting stent (PCI-eS), there is also an indication for aspirin and clopidogrel treatment, according to the ESC Guidelines. However, triple therapy has been known to increase the risk of bleeding complications. Unfortunately, there is little prospective data available to resolve this issue. Therefore, it is imperative that an optimal therapy for AF patients with indications of both anticoagulation and antiplatelet intervention to prevent thrombotic complications without increasing the risk of bleeding is found.. This prospective, randomized, multicenter study is going to assess the hypothesis that in persistent or permanent AF patients (score of CHA₂DS₂VASc≥2) after PCI-eS, the combination therapy of oral anticoagulation (warfarin) and ticagrelor (90 mg/bid) could reduce the risk of bleeding events.. A multicenter, active-controlled, open-label, randomized trial is to be performed to evaluate dual antithrombotic therapy (ticagrelor+warfarin) in persistent or permanent AF patients (score of CHA₂DS₂VASc≥2) after PCI-eS versus the combination of triple antithrombosis (clopidogrel+aspirin+warfarin). The primary endpoint is the overall bleeding up to 6 months, according to TIMI criteria and classifications. The secondary endpoints are the major bleeding events up to 6 months, according to TIMI criteria. The sample size is estimated at 296.. This study is intended to provide information about the safety characteristics of warfarin and ticagrelor in persistent or permanent AF patients after PCI-eS. No prospective randomized study has been conducted on the issue of antithrombotic therapy using warfarin and ticagrelor in these patients. Therefore, the MANJUSRI trial will help to explore and determine a new potential therapeutic regimen for AF patients after PCI-eS.. Clinical Trials.gov # NCT02206815, registered July 30, 2014.

Topics: Adenosine; Adolescent; Adult; Aged; Aspirin; Atrial Fibrillation; Clopidogrel; Drug Therapy, Combination; Drug-Eluting Stents; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Research Design; Ticagrelor; Ticlopidine; Warfarin; Young Adult

Limited data are available on high platelet reactivity (HPR) rate early post fibrinolysis, while no effective way to overcome it has been proposed. In this context, we aimed to compare ticagrelor versus high dose clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) who exhibit HPR post fibrinolysis. In a prospective, randomized, parallel design, 3-center study, 56 STEMI patients, out of 83 (67.5 %) screened, who presented with HPR (PRU ≥ 208 by VerifyNow) 3-48 h post fibrinolysis and prior to coronary angiography were allocated to ticagrelor 180 mg loading dose (LD)/90 mg bid maintenance dose (MD) or clopidogrel 600 mg LD/150 mg MD. Platelet reactivity was assessed at randomization (Hour 0), at Hour 2, Hour 24 and pre-discharge. The primary endpoint of platelet reactivity (in PRU) at Hour 2 was significantly lower for ticagrelor compared to clopidogrel with a least square mean difference (95 % confidence interval) of -141.7 (-173.4 to -109.9), p < 0.001. HPR rates at Hour 2 and 24 were significantly lower for ticagrelor versus clopidogrel (14.3 vs. 82.1 %, p < 0.001 and 0 vs. 25.0 %, p = 0.01 respectively), though not significantly different pre-discharge. In-hospital Bleeding Academic Research Consortium type ≥2 bleeding occurred in 1 and 2 clopidogrel and ticagrelor-treated patients, respectively. In STEMI patients, post fibrinolysis HPR is common. Ticagrelor treats HPR more effectively compared to high dose clopidogrel therapy. Although antiplatelet regimens tested in this study were well tolerated, this finding should be considered only exploratory.

Topics: Adenosine; Aged; Blood Platelets; Clopidogrel; Female; Fibrinolysis; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Activation; Prospective Studies; Ticagrelor; Ticlopidine

The potential benefit of dual antiplatelet therapy beyond 1 year after a myocardial infarction has not been established. We investigated the efficacy and safety of ticagrelor, a P2Y12 receptor antagonist with established efficacy after an acute coronary syndrome, in this context.. We randomly assigned, in a double-blind 1:1:1 fashion, 21,162 patients who had had a myocardial infarction 1 to 3 years earlier to ticagrelor at a dose of 90 mg twice daily, ticagrelor at a dose of 60 mg twice daily, or placebo. All the patients were to receive low-dose aspirin and were followed for a median of 33 months. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was Thrombolysis in Myocardial Infarction (TIMI) major bleeding.. The two ticagrelor doses each reduced, as compared with placebo, the rate of the primary efficacy end point, with Kaplan-Meier rates at 3 years of 7.85% in the group that received 90 mg of ticagrelor twice daily, 7.77% in the group that received 60 mg of ticagrelor twice daily, and 9.04% in the placebo group (hazard ratio for 90 mg of ticagrelor vs. placebo, 0.85; 95% confidence interval [CI], 0.75 to 0.96; P=0.008; hazard ratio for 60 mg of ticagrelor vs. placebo, 0.84; 95% CI, 0.74 to 0.95; P=0.004). Rates of TIMI major bleeding were higher with ticagrelor (2.60% with 90 mg and 2.30% with 60 mg) than with placebo (1.06%) (P<0.001 for each dose vs. placebo); the rates of intracranial hemorrhage or fatal bleeding in the three groups were 0.63%, 0.71%, and 0.60%, respectively.. In patients with a myocardial infarction more than 1 year previously, treatment with ticagrelor significantly reduced the risk of cardiovascular death, myocardial infarction, or stroke and increased the risk of major bleeding. (Funded by AstraZeneca; PEGASUS-TIMI 54 ClinicalTrials.gov number, NCT01225562.).

Topics: Adenosine; Aged; Aspirin; Cardiovascular Diseases; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk; Secondary Prevention; Ticagrelor

There is insufficient data on the efficacy of prasugrel and ticagrelor in Korean patients with ST-segment elevation myocardial infarction (STEMI).. I n the current double-blind, prospective pilot study, 39 patients with STEMI undergoing primary percutaneous coronary intervention were randomized to receive prasugrel 60 mg loading dose (LD) followed by 10 mg daily maintenance dose (n=19), or ticagrelor 180 mg LD followed by 90 mg twice daily maintenance dose (n=20). We assessed platelet reactivity with the VerifyNow and Vasodilator-Stimulated Phosphoprotein (VASP) P2Y12 assays. Compared to baseline platelet reactivity, both prasugrel and ticagrelor groups achieved similar and significantly lower P2Y12 reaction units (PRU) (259 [IQR: 230 to 281] vs. 28 [12 to 55] for prasugrel; 261 [196 to 286] vs. 43 [11 to 61] for ticagrelor), and platelet reactivity indexes (PRI) (51.2% [39.3 to 61.3] vs. 8.1% [6.1 to 14.7] for prasugrel; 47.5% [38.4 to 50.4] vs. 11.2% [7.1 to 15.5] for ticagrelor, all P values <0.001) at 48 h post-LD. Most patients had low platelet reactivity with 95% PRU values <85 and 82% with PRI <16%.. Both prasugrel and ticagrelor were effective for platelet inhibition in Korean STEMI patients with almost no patients exhibiting high platelet reactivity at 48 h after the LD. Our finding of a high number of patients with very low platelet reactivity deserves further studies to assess the safety of the drugs (Prasugrel and Ticagrelor in ST-segment Elevation Myocardial Infarction Study, NCT02075125).

Topics: Adenosine; Adult; Aged; Asian People; Aspirin; Cardiac Catheterization; Double-Blind Method; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Pilot Projects; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Postoperative Complications; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Republic of Korea; Sample Size; Thrombophilia; Thrombosis; Ticagrelor

Optimal antithrombotic strategy for patients with concomitant coronary artery disease and atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) is still controversial, and the role of novel antithrombotic agents has nerve been tested. Therefore, the aim of this study is to evaluate and overall safety and efficacy profile of the combination of rivaroxaban and ticagrelor in this particular population.. The RT-AF study is an open-label, randomized, active-controlled, multicenter clinical trial with up to 420 subjects enrolled in 5 centers. Eligible patients, who have a history or new onset paroxysmal, persistent, or permanent non-valvular AF, referred to the study centers with indications for PCI will be randomly assigned to receive triple therapy (including warfarin, clopidogrel and aspirin) or dual therapy (rivaroxaban and ticagrelor). All subjects will have clinical follow-up at discharge, at 30 days, 6 months and 12 months. The primary end point is major or clinically relevant non-major bleeding events at 12 months. The major secondary end point is the composite efficacy outcome of death, myocardial infarction, stent thrombosis and ischemic stroke.. The study will be sufficiently powered to provide data primarily regarding the safety of dual therapy with rivaroxaban and ticagrelor over the traditional triple therapy in patients with AF undergoing PCI at 12 months. It will also provide important information regarding the efficacy of the two different antithrombotic regimens. (ClinicalTrials.gov identifier: NCT02334254).

Topics: Adenosine; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Drug Therapy, Combination; Hemorrhage; Humans; Percutaneous Coronary Intervention; Research Design; Rivaroxaban; Ticagrelor; Ticlopidine; Warfarin

In the PLATO trial, ticagrelor was superior to clopidogrel in reducing cardiovascular events among patients with acute coronary syndrome (ACS) at the expense of increased nonfatal bleeding. Because Asian patients, when compared with non-Asian patients, are believed to be more susceptible to bleeding, we evaluated the effects of ticagrelor compared with clopidogrel in Asian (n=1,106) and non-Asian (n=17,515) patients with acute coronary syndrome enrolled in the PLATO study.. Interaction between Asian/non-Asian and primary efficacy end point (a composite of vascular death, myocardial infarction, and stroke) and net clinical benefit (composite of primary efficacy end point and coronary artery bypass graft [CABG] surgery or non-CABG-related major bleeding) were evaluated with a Cox proportional hazards model. Baseline demographics and comorbidities were different between Asians and non-Asians. The overall cardiovascular event rates were higher in Asians, but bleeding rates were similar. Despite these observed differences, the effects of ticagrelor versus clopidogrel were not significantly different between Asians and non-Asians with respect to the primary efficacy outcome (hazard ratio for Asians vs non-Asians, 0.84 [95% CI 0.61-1.17] vs 0.85 [95% CI 0.77-0.93], P=.974), net clinical benefit (0.85 [95% CI 0.65-1.11] vs 0.93 [95% CI 0.86-0.99], P=.521), or individual efficacy end points. There was no significant interaction for bleeding (PLATO major bleeding, 1.02 [95% CI 0.70-1.49] vs 1.04 [95% CI 0.95-1.14], P=.938) and other related adverse events with ticagrelor compared with clopidogrel between Asians and non-Asians.. We observed consistency of effects in Asian patients receiving ticagrelor and clopidogrel in the PLATO study. The relatively modest number of Asian patients in this analysis supports further investigation of larger cohorts to confirm our observations.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Asian People; Clopidogrel; Double-Blind Method; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Ticagrelor; Ticlopidine; Treatment Outcome

Based on animal and human data, phosphoinositide 3-kinase (PI3K)β is a promising antithrombotic target. However, the relation between efficacy and bleeding when combined with current antiplatelet therapies is unclear.. To strengthen the PI3Kβ target validation using the short-acting inhibitor AZD6482 alone and in different combinations with P2Y12 and cyclooxygenase (COX)-1 inhibition in vitro (human platelets), in vivo (dog), and in healthy subjects.. Evaluation of complete target inhibition of PI3Kβ (by AZD6482), P2Y12 (by ticagrelor), and COX-1 (by aspirin) alone and in the different combinations vs. concentration responses for a panel of platelet agonists in vitro (adenosine diphosphate, collagen, thrombin receptor activating peptide) indicates that the rank order of antiplatelet efficacy is P2Y12  > PI3Kβ > COX-1 as monotherapy and P2Y12 plus PI3Kβ > P2Y12 plus COX-1 > PI3Kβ plus COX-1 as dual therapy, with little additional effect with triple therapy. Use of a conscious dog model to assess ex vivo antiplatelet effect in parallel with bleeding time prolongation (standard incision in the ear) confirms the wide separation of efficacy vs. bleeding for PI3Kβ inhibition and that this separation is reduced when combined with aspirin and more reduced when combined with clopidogrel. In healthy subjects, AZD6482, in combination with aspirin, shows a potential for greater antiplatelet potency but less bleeding potential compared with clopidogrel plus aspirin.. PI3Kβ inhibition, in comparison with P2Y12 and COX-1, delivers medium antiplatelet effect but with minimal bleeding. PI3Kβ inhibition, in combination with aspirin, in healthy subjects, provides a potential for greater overall antiplatelet effect compared with clopidogrel plus aspirin, but with significantly less bleeding potential.

Topics: Adenosine; Adult; Animals; Aspirin; Blood Platelets; Cross-Over Studies; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Dogs; Dose-Response Relationship, Drug; Drug Therapy, Combination; Hemorrhage; Humans; Male; Models, Animal; ortho-Aminobenzoates; Phosphatidylinositol 3-Kinase; Phosphoinositide-3 Kinase Inhibitors; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Protein Kinase Inhibitors; Purinergic P2Y Receptor Antagonists; Pyrimidinones; Receptors, Purinergic P2Y12; Sweden; Ticagrelor; Young Adult

Few data on the relative efficacy and safety of new P2Y12inhibitors such as prasugrel and ticagrelor in Japanese, Taiwanese and South Korean patients with acute coronary syndromes (ACS) exist.. The multicenter, double-blind, randomized PHILO trial compared the safety and efficacy of ticagrelor vs. clopidogrel in 801 patients with ACS (Japanese, n=721; Taiwanese, n=35; South Korean, n=44; unknown ethnicity, n=1). All were planned to undergo percutaneous coronary intervention and randomized within 24 h of symptom onset. Primary safety and efficacy endpoints were time to first occurrence of any major bleeding event and to any event from the composite of myocardial infarction, stroke or death from vascular causes, respectively.At 12 months, overall major bleeding occurred in 10.3% of ticagrelor-treated patients and in 6.8% of clopidogrel-treated patients (hazard ratio (HR), 1.54; 95% confidence interval (CI): 0.94-2.53); the composite primary efficacy endpoint occurred in 9.0% and in 6.3% of ticagrelor- and clopidogrel-treated patients, respectively (HR, 1.47; 95% CI: 0.88-2.44). For both analyses, the difference between groups was not statistically significant.. In ACS patients from Japan, Taiwan and South Korea, event rates of primary safety and efficacy endpoints were higher, albeit not significantly, in ticagrelor-treated patients compared with clopidogrel-treated patients. This observation could be explained by the small sample size, imbalance in clinical characteristics and low number of events in the PHILO population.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Asian People; Clopidogrel; Double-Blind Method; Female; Hemorrhage; Humans; Japan; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Republic of Korea; Risk Factors; Stroke; Taiwan; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Patients with chronic obstructive pulmonary disease (COPD) experiencing acute coronary syndromes (ACS) are at high risk for clinical events. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor versus clopidogrel reduced the primary endpoint of death from vascular causes, myocardial infarction, or stroke after ACS, but increased the incidence of dyspnea, which may lead clinicians to withhold ticagrelor from COPD patients.. In 18 624 patients with ACS randomized to treatment with ticagrelor or clopidogrel, history of COPD was recorded in 1085 (5.8%). At 1 year, the primary endpoint occurred in 17.7% of patients with COPD versus 10.4% in those without COPD (P<0.001). The 1-year event rate for the primary endpoint in COPD patients treated with ticagrelor versus clopidogrel was 14.8% versus 20.6% (hazard ratio [HR]=0.72; 95% confidence interval [CI]: 0.54 to 0.97), for death from any cause 8.4% versus 12.4% (HR=0.70; 95% CI: 0.47 to 1.04), and for PLATO-defined major bleeding rates at 1 year 14.6% versus 16.6% (HR=0.85; 95% CI: 0.61 to 1.17). Dyspnea occurred more frequently with ticagrelor (26.1% vs. 16.3%; HR=1.71; 95% CI: 1.28 to 2.30). There was no differential increase in the relative risk of dyspnea compared to non-COPD patients (HR=1.85). No COPD status-by-treatment interactions were found, showing consistency with the main trial results.. In this post-hoc analysis, COPD patients experienced high rates of ischemic events. Ticagrelor versus clopidogrel reduced and substantially decreased the absolute risk of ischemic events (5.8%) in COPD patients, without increasing overall major bleeding events. The benefit-risk profile supports the use of ticagrelor in patients with ACS and concomitant COPD.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Dyspnea; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Platelet Aggregation Inhibitors; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Risk Factors; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

The aim of this study was to assess the relationship between sex and clinical outcomes and treatment-related complications in patients with ST-elevation or non-ST-elevation acute coronary syndromes (ACS) randomized to treatment with ticagrelor or clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) trial.. The associations between sex subgroup and the primary composite outcomes, secondary outcomes, and major bleeding endpoints as well as interaction of sex subgroup with treatment effects were analysed using Cox proportional-hazards models.. Sex was not significantly associated with the probability of the primary composite endpoint [adjusted hazard ratio (HR): 1.02 (0.91-1.16)], or other adverse cardiovascular endpoints. Ticagrelor was similarly more effective than clopidogrel in reducing rates of the primary endpoint in women 11.2 vs. 13.2% [adjusted HR: 0.88 (0.74-1.06)] and men 9.4 vs. 11.1% [adjusted HR: 0.86 (0.76-0.97)] (interaction P-value 0.78), all-cause death in women 5.8 vs. 6.8% [adjusted HR: 0.90 (0.69-1.16)] and men 4.0 vs. 5.7% [adjusted HR: 0.80 (0.67-0.96)] (interaction P-value 0.49), and definite stent thrombosis in women 1.2 vs. 1.4% [adjusted HR: 0.71 (0.36-1.38)] and men 1.4 vs. 2.1% [adjusted HR: 0.63 (0.45-0.89)] (interaction P-value 0.78). The treatments did not differ for PLATO-defined overall major bleeding complications in women [adjusted HR: 1.01 (0.83-1.23)] or men [adjusted HR: 1.10 (0.98-1.24)]. Sex had no significant association with these outcomes (interactions P = 0.43-0.88).. Female sex is not an independent risk factor for adverse clinical outcomes in moderate-to-high risk ACS patients. Ticagrelor has a similar efficacy and safety profile in men and women.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Dose-Response Relationship, Drug; Double-Blind Method; Female; Graft Occlusion, Vascular; Hemorrhage; Humans; Male; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; Recurrence; Sex Factors; Stents; Stroke; Ticagrelor; Ticlopidine; Treatment Outcome

The optimal platelet inhibition strategy for ACS patients managed without revascularization is unknown. We aimed to evaluate efficacy and safety of ticagrelor vs. clopidogrel in the non-ST-elevation acute coronary syndrome (NSTE-ACS) subgroup of the PLATO trial, in the total cohort, and in the subgroups managed with and without revascularization within 10 days of randomization.. We performed a retrospective analysis of the primary endpoint of cardiovascular death/myocardial infarction/stroke. Among 18 624 PLATO patients, 11 080 (59%) were categorized as NSTE-ACS at randomization. During the initial 10 days, 74% had angiography, 46% PCI, and 5% CABG. In NSTE-ACS patients, the primary endpoint was reduced with ticagrelor vs. clopidogrel [10.0 vs. 12.3%; hazard ratio (HR) 0.83; 95% confidence interval (CI) = 0.74-0.93], as was myocardial infarction (6.6 vs. 7.7%; HR 0.86; 95% CI = 0.74-0.99), cardiovascular death (3.7 vs. 4.9%; HR 0.77; 95% CI = 0.64-0.93), and all-cause death (4.3 vs. 5.8%; HR 0.76; 95% CI = 0.64-0.90). Major bleeding rate was similar between treatment groups (13.4 vs. 12.6%; HR 1.07; 95% CI = 0.95-1.19), but ticagrelor was associated with an increase in non-CABG major bleeding (4.8 vs. 3.8%; HR 1.28; 95% CI = 1.05-1.56). Within the first 10 days, 5366 (48.4%) patients were managed without revascularization. Regardless of revascularization or not, ticagrelor consistently reduced the primary outcome (HR 0.86 vs. 0.85, interaction P = 0.93), and all-cause death (HR 0.75 vs. 0.73, interaction P = 0.89) with no significant increase in overall major bleeding.. In patients with NSTE-ACS, benefit of ticagrelor over clopidogrel in reducing ischaemic events and total mortality was consistent with the overall PLATO trial, independent of actually performed revascularization during the initial 10 days.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Myocardial Infarction; Myocardial Revascularization; Platelet Aggregation Inhibitors; Retrospective Studies; Ticagrelor; Ticlopidine; Treatment Outcome

Two studies assessing ticagrelor pharmacokinetics, pharmacodynamics, and tolerability in healthy Japanese and Caucasian volunteers.. Single-ascending dose (SAD) study: Japanese (n = 20) and Caucasians (n = 20) received single doses of ticagrelor (50, 100, 200, 300, 400, and 600 mg) or placebo. Multiple-ascending dose (MAD) study: Japanese (n = 36) and Caucasians (n = 36) received single doses of 100 mg or 300 mg ticagrelor (day 1), twice-daily 100 mg or 300 mg ticagrelor, or placebo (days 4 – 9), and single doses of 100 mg or 300 mg ticagrelor (day 10).. Exposure to ticagrelor and its active metabolite, AR-C124910XX, was generally higher in Japanese vs. Caucasians. In the SAD study, area under the plasma concentration-time curve (AUC) values were 33% (ticagrelor) and 55% (AR-C124910XX) greater in Japanese vs. Caucasians following 600 mg ticagrelor. In the MAD study, AUC values of ticagrelor and AR-C124910XX following multiple doses of ticagrelor 100 mg and 300 mg were statistically significantly greater (33 - 48%) in Japanese vs. Caucasians. In both groups, mean peak inhibition of platelet aggregation was > 86% after single doses (>= 100 mg ticagrelor) and > 84% after multiple doses. Bleeding times were >= 60 minutes in more Japanese than Caucasians with multiple dosing of 100 mg and 300 mg ticagrelor Adverse events were similar between groups (mild-to-moderate intensity).. The pharmacokinetics and tolerability of ticagrelor were broadly similar in Japanese and Caucasians, although exposure was slightly greater in Japanese volunteers. Ticagrelor was generally well tolerated.

Topics: Adenosine; Adult; Area Under Curve; Asian People; Biotransformation; Double-Blind Method; Drug Administration Schedule; Female; Half-Life; Hemorrhage; Humans; Japan; Male; Metabolic Clearance Rate; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Purinergic P2Y Receptor Antagonists; Ticagrelor; United States; White People; Young Adult

Platelet reactivity (PR) and bleeding events following therapy with ticagrelor vs prasugrel have not been adequately studied. We aimed to compare PR and bleeding events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) while on ticagrelor vs prasugrel for one month. Consecutive patients who were discharged either on ticagrelor 90 mg bid maintenance dose (MD) or prasugrel 10 mg MD were invited for PR assessment (VerifyNow, in PRU) at one month. High PR (HPR) was defined as >208 PRU. Bleeding events [Bleeding Academic Research Consortium (BARC) classification] were monitored. Out of 937 screened patients, 512 were analysed, 278 under ticagrelor MD and 234 under prasugrel MD. PR at 30 days (C-statistic of the propensity score model 0.63, 0.58-0.67 95% CI, p<0.001) was lower when on ticagrelor compared with prasugrel (33.3, 95% CI 29.3-37.3 vs 84.6, 95% CI 73.6-95.6, p<0.001). In the analysed population more BARC type 1 bleeding events were observed with ticagrelor compared to prasugrel (36.7% vs 28.2%, p=0.047). In 221 propensity score matched pairs, BARC type 1 bleeding rate was marginally higher in ticagrelor vs prasugrel treated patients (35.7% vs 27.1%, p=0.05). BARC type ≥2 events did not differ between groups 5 (2.3%) vs 5 (2.3%). HPR rate was higher for prasugrel-treated patients (5.4% vs 0%, p<0.001). In conclusion, in patients with ACS undergoing PCI, ticagrelor MD produces a significantly higher platelet inhibition compared to prasugrel MD. This pharmacodynamic difference might be associated with more nuisance bleeding events with ticagrelor use.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Female; Hemorrhage; Humans; Maintenance Chemotherapy; Male; Middle Aged; Percutaneous Coronary Intervention; Piperazines; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Thiophenes; Ticagrelor; Treatment Outcome

The direct-acting platelet P2Y12 receptor antagonist ticagrelor can reduce the incidence of major adverse cardiovascular events when administered at hospital admission to patients with ST-segment elevation myocardial infarction (STEMI). Whether prehospital administration of ticagrelor can improve coronary reperfusion and the clinical outcome is unknown.. We conducted an international, multicenter, randomized, double-blind study involving 1862 patients with ongoing STEMI of less than 6 hours' duration, comparing prehospital (in the ambulance) versus in-hospital (in the catheterization laboratory) treatment with ticagrelor. The coprimary end points were the proportion of patients who did not have a 70% or greater resolution of ST-segment elevation before percutaneous coronary intervention (PCI) and the proportion of patients who did not have Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography. Secondary end points included the rates of major adverse cardiovascular events and definite stent thrombosis at 30 days.. The median time from randomization to angiography was 48 minutes, and the median time difference between the two treatment strategies was 31 minutes. The two coprimary end points did not differ significantly between the prehospital and in-hospital groups. The absence of ST-segment elevation resolution of 70% or greater after PCI (a secondary end point) was reported for 42.5% and 47.5% of the patients, respectively. The rates of major adverse cardiovascular events did not differ significantly between the two study groups. The rates of definite stent thrombosis were lower in the prehospital group than in the in-hospital group (0% vs. 0.8% in the first 24 hours; 0.2% vs. 1.2% at 30 days). Rates of major bleeding events were low and virtually identical in the two groups, regardless of the bleeding definition used.. Prehospital administration of ticagrelor in patients with acute STEMI appeared to be safe but did not improve pre-PCI coronary reperfusion. (Funded by AstraZeneca; ATLANTIC ClinicalTrials.gov number, NCT01347580.).

Topics: Adenosine; Aged; Anticoagulants; Clopidogrel; Coronary Angiography; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Emergency Medical Services; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Reperfusion; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; Time-to-Treatment

Few data exist about the implementation of contemporary oral antiplatelet treatment guidelines in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).. GReek AntiPlatelet rEgistry (GRAPE), initiated on January 2012, is a prospective, observational, multicenter cohort study focusing on contemporary use of P2Y12 inhibitors. In 1434 patients we evaluated appropriateness of P2Y12 selection initially and at discharge by applying an eligibility-assessing algorithm based on P2Y12 inhibitors' contraindications/specific warnings and precautions.. Appropriate, less preferable and inappropriate P2Y12 inhibitor selections were made initially in 45.8%, 47.2% and 6.6% and at discharge in 64.1%, 29.2% and 6.6% of patients, respectively. The selection of clopidogrel was most commonly less preferable, both initially (69.7%) and at discharge (75.6%). Appropriate selection of newer agents was high initially (79.2%-82.8%), with further increase as selection at discharge (89.4%-89.8%). Inappropriate selection of the newer agents was 17.2%-20.8% initially, decreasing to 10.2%-10.6% at discharge. Conditions and co-medications related to increased bleeding risk, presentation with ST elevation myocardial infarction and the absence of reperfusion within the first 24h were the most powerful predictors of appropriate P2Y12 selection initially, whereas age ≥75 years, conditions and co-medications related to increased bleeding risk and regional trends mostly affected appropriate P2Y12 selection at discharge.. In GRAPE, adherence with the recently released guidelines on oral antiplatelet therapy was satisfactory. Clopidogrel was most commonly used as a less preferable selection, while prasugrel or ticagrelor selection was mostly appropriate. Certain factors may predict initial and at discharge guideline implementation. Clinical Trial Registration-clinicaltrials.gov Identifier: NCT01774955 http://clinicaltrials.gov/.

Topics: Acute Coronary Syndrome; Adenosine; Administration, Oral; Aged; Clopidogrel; Combined Modality Therapy; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Practolol; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Registries; Thiophenes; Ticagrelor; Ticlopidine

Patients with prior coronary artery bypass graft surgery (CABG) who present with an acute coronary syndrome have a high risk for recurrent events. Whether intensive antiplatelet therapy with ticagrelor might be beneficial compared with clopidogrel is unknown. In this substudy of the PLATO trial, we studied the effects of randomized treatment dependent on history of CABG.. Patients participating in PLATO were classified according to whether they had undergone prior CABG. The trial's primary and secondary end points were compared using Cox proportional hazards regression.. Of the 18,613 study patients, 1,133 (6.1%) had prior CABG. Prior-CABG patients had more high-risk characteristics at study entry and a 2-fold increase in clinical events during follow-up, but less major bleeding. The primary end point (composite of cardiovascular death, myocardial infarction, and stroke) was reduced to a similar extent by ticagrelor among patients with (19.6% vs 21.4%; adjusted hazard ratio [HR], 0.91 [0.67, 1.24]) and without (9.2% vs 11.0%; adjusted HR, 0.86 [0.77, 0.96]; P(interaction) = .73) prior CABG. Major bleeding was similar with ticagrelor versus clopidogrel among patients with (8.1% vs 8.7%; adjusted HR, 0.89 [0.55, 1.47]) and without (11.8% vs 11.4%; HR, 1.08 [0.98, 1.20]; P(interaction) = .46) prior CABG.. Prior-CABG patients presenting with acute coronary syndrome are a high-risk cohort for death and recurrent cardiovascular events but have a lower risk for major bleeding. Similar to the results in no-prior-CABG patients, ticagrelor was associated with a reduction in ischemic events without an increase in major bleeding.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Coronary Artery Bypass; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Proportional Hazards Models; Purinergic P2Y Receptor Antagonists; Risk Factors; Stroke; Survival Analysis; Ticagrelor; Treatment Outcome

Elderly patients with acute coronary syndrome are at high risk of recurrent ischemic events and death, and for both antithrombotic therapy and catheter-based complications. This prespecified analysis investigates the effect and treatment-related complications of ticagrelor versus clopidogrel in elderly patients (≥75 years of age) with acute coronary syndrome compared with those <75 years of age.. The association between age and the primary composite outcome, as well as major bleeding were evaluated in the PLATelet inhibition and patient Outcomes (PLATO) trial using Cox proportional hazards. Similar models were used to evaluate the interaction of age with treatment effects. Hazard ratios were adjusted for baseline characteristics. The clinical benefit of ticagrelor over clopidogrel was not significantly different between patients aged ≥75 years of age (n=2878) and those <75 years of age (n=15 744) with respect to the composite of cardiovascular death, myocardial infarction, or stroke (interaction P=0.56), myocardial infarction (P=0.33), cardiovascular death (P=0.47), definite stent thrombosis (P=0.81), or all-cause mortality (P=0.76). No increase in PLATO-defined overall major bleeding with ticagrelor versus clopidogrel was observed in patients aged ≥75 years (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27) or patients aged <75 years (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15). Dyspnea and ventricular pauses were more common during ticagrelor than clopidogrel treatment, with no evidence of an age-by-treatment interaction.. The significant clinical benefit and overall safety of ticagrelor compared with clopidogrel in acute coronary syndrome patients in the PLATO cohort were not found to depend on age.

Topics: Acute Coronary Syndrome; Adenosine; Age Factors; Aged; Cardiovascular Diseases; Chi-Square Distribution; Clopidogrel; Double-Blind Method; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Patient Safety; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Stents; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

AIMS More intense platelet-directed therapy for acute coronary syndrome (ACS) may increase bleeding risk. The aim of the current analysis was to determine the rate, clinical impact, and predictors of major and fatal bleeding complications in the PLATO study. METHODS AND RESULTS PLATO was a randomized, double-blind, active control international, phase 3 clinical trial in patients with acute ST elevation and non-ST-segment elevation ACS. A total of 18 624 patients were randomized to either ticagrelor, a non-thienopyridine, reversibly binding platelet P2Y(12) receptor antagonist, or clopidogrel in addition to aspirin. Patients randomized to ticagrelor and clopidogrel had similar rates of PLATO major bleeding (11.6 vs. 11.2%; P = 0.43), TIMI major bleeding (7.9 vs. 7.7%, P = 0.56) and GUSTO severe bleeding (2.9 vs. 3.1%, P = 0.22). Procedure-related bleeding rates were also similar. Non-CABG major bleeding (4.5 vs. 3.8%, P = 0.02) and non-procedure-related major bleeding (3.1 vs. 2.3%, P = 0.05) were more common in ticagrelor-treated patients, primarily after 30 days on treatment. Fatal bleeding and transfusion rates did not differ between groups. There were no significant interactions for major bleeding or combined minor plus major bleeding between treatment groups and age ≥75 years, weight <60 kg, region, chronic kidney disease, creatinine clearance <60 mL/min, aspirin dose >325 mg on the day of randomization, pre-randomization clopidogrel administration, or clopidogrel loading dose. CONCLUSION Ticagrelor compared with clopidogrel was associated with similar total major bleeding but increased non-CABG and non-procedure-related major bleeding, primarily after 30 days on study drug treatment. Fatal bleeding was low and did not differ between groups.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aspirin; Clopidogrel; Coronary Artery Bypass; Double-Blind Method; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Stroke; Ticagrelor; Ticlopidine; Treatment Outcome

patients with diabetes mellitus (DM) have high platelet reactivity and are at increased risk of ischaemic events and bleeding post-acute coronary syndromes (ACS). In the PLATelet inhibition and patient Outcomes (PLATO) trial, ticagrelor reduced the primary composite endpoint of cardiovascular death, myocardial infarction, or stroke, but with similar rates of major bleeding compared with clopidogrel. We aimed to investigate the outcome with ticagrelor vs. clopidogrel in patients with DM or poor glycaemic control.. we analysed patients with pre-existing DM (n = 4662), including 1036 patients on insulin, those without DM (n = 13 951), and subgroups based on admission levels of haemoglobin A1c (HbA1c; n = 15 150). In patients with DM, the reduction in the primary composite endpoint (HR: 0.88, 95% CI: 0.76-1.03), all-cause mortality (HR: 0.82, 95% CI: 0.66-1.01), and stent thrombosis (HR: 0.65, 95% CI: 0.36-1.17) with no increase in major bleeding (HR: 0.95, 95% CI: 0.81-1.12) with ticagrelor was consistent with the overall cohort and without significant diabetes status-by-treatment interactions. There was no heterogeneity between patients with or without ongoing insulin treatment. ticagrelor reduced the primary endpoint, all-cause mortality, and stent thrombosis in patients with HbA1c above the median (HR: 0.80, 95% CI: 0.70-0.91; HR: 0.78, 95% CI: 0.65-0.93; and HR: 0.62, 95% CI: 0.39-1.00, respectively) with similar bleeding rates (HR: 0.98, 95% CI: 0.86-1.12).. ticagrelor, when compared with clopidogrel, reduced ischaemic events in ACS patients irrespective of diabetic status and glycaemic control, without an increase in major bleeding events.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Blood Glucose; Clopidogrel; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glycated Hemoglobin; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Ticagrelor; Ticlopidine; Treatment Outcome

Reduced renal function is associated with a poorer prognosis and increased bleeding risk in patients with acute coronary syndromes and may therefore alter the risk-benefit ratio with antiplatelet therapies. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor compared with clopidogrel reduced the primary composite end point of cardiovascular death, myocardial infarction, and stroke at 12 months but with similar major bleeding rates.. Central laboratory serum creatinine levels were available in 15 202 (81.9%) acute coronary syndrome patients at baseline, and creatinine clearance, estimated by the Cockcroft Gault equation, was calculated. In patients with chronic kidney disease (creatinine clearance <60 mL/min; n=3237), ticagrelor versus clopidogrel significantly reduced the primary end point to 17.3% from 22.0% (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.65 to 0.90) with an absolute risk reduction greater than that of patients with normal renal function (n=11 965): 7.9% versus 8.9% (HR, 0.90; 95% CI, 0.79 to 1.02). In patients with chronic kidney disease, ticagrelor reduced total mortality (10.0% versus 14.0%; HR, 0.72; 95% CI, 0.58 to 0.89). Major bleeding rates, fatal bleedings, and non-coronary bypass-related major bleedings were not significantly different between the 2 randomized groups (15.1% versus 14.3%; HR, 1.07; 95% CI, 0.88 to 1.30; 0.34% versus 0.77%; HR, 0.48; 95% CI, 0.15 to 1.54; and 8.5% versus 7.3%; HR, 1.28; 95% CI, 0.97 to 1.68). The interactions between creatinine clearance and randomized treatment on any of the outcome variables were nonsignificant.. In acute coronary syndrome patients with chronic kidney disease, ticagrelor compared with clopidogrel significantly reduces ischemic end points and mortality without a significant increase in major bleeding but with numerically more non-procedure-related bleeding.. URL:http://www.clinicatrials.gov. Unique identifier: NCT00391872.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Cardiovascular Diseases; Chronic Disease; Clopidogrel; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Kidney Diseases; Male; Middle Aged; Outcome Assessment, Health Care; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Factors; Ticagrelor; Ticlopidine; Treatment Outcome

Aspirin and clopidogrel are recommended for patients with acute coronary syndromes (ACS) or undergoing coronary stenting. Ticagrelor, a reversible oral P2Y12-receptor antagonist, provides faster, greater, and more consistent platelet inhibition than clopidogrel and may be useful for patients with acute ST-segment elevation (STE) ACS and planned primary percutaneous coronary intervention.. Platelet Inhibition and Patient Outcomes (PLATO), a randomized, double-blind trial, compared ticagrelor with clopidogrel for the prevention of vascular events in 18 624 ACS patients. This report concerns the 7544 ACS patients with STE or left bundle-branch block allocated to either ticagrelor 180-mg loading dose followed by 90 mg twice daily or clopidogrel 300-mg loading dose (with provision for 300 mg clopidogrel at percutaneous coronary intervention) followed by 75 mg daily for 6 to 12 months. The reduction of the primary end point (myocardial infarction, stroke, or cardiovascular death) with ticagrelor versus clopidogrel (10.8% versus 9.4%; hazard ratio [HR], 0.87; 95% confidence interval, 0.75 to 1.01; P=0.07) was consistent with the overall PLATO results. There was no interaction between presentation with STE/left bundle-branch block and randomized treatment (interaction P=0.29). Ticagrelor reduced several secondary end points, including myocardial infarction alone (HR, 0.80; P=0.03), total mortality (HR, 0.82; P=0.05), and definite stent thrombosis (HR, 0.66; P=0.03). The risk of stroke, low in both groups, was higher with ticagrelor (1.7% versus 1.0%; HR,1.63; 95% confidence interval, 1.07 to 2.48; P=0.02). Ticagrelor did not affect major bleeding (HR, 0.98; P=0.76).. In patients with STE-ACS and planned primary percutaneous coronary intervention, the effects of ticagrelor were consistent with those observed in the overall PLATO trial.. URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00391872.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Angioplasty, Balloon, Coronary; Clopidogrel; Coronary Thrombosis; Electrocardiography; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk Factors; Ticagrelor; Ticlopidine; Treatment Outcome

Ticagrelor is an oral, reversible, direct-acting inhibitor of the adenosine diphosphate receptor P2Y12 that has a more rapid onset and more pronounced platelet inhibition than clopidogrel.. In this multicenter, double-blind, randomized trial, we compared ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) and clopidogrel (300-to-600-mg loading dose, 75 mg daily thereafter) for the prevention of cardiovascular events in 18,624 patients admitted to the hospital with an acute coronary syndrome, with or without ST-segment elevation.. At 12 months, the primary end point--a composite of death from vascular causes, myocardial infarction, or stroke--had occurred in 9.8% of patients receiving ticagrelor as compared with 11.7% of those receiving clopidogrel (hazard ratio, 0.84; 95% confidence interval [CI], 0.77 to 0.92; P<0.001). Predefined hierarchical testing of secondary end points showed significant differences in the rates of other composite end points, as well as myocardial infarction alone (5.8% in the ticagrelor group vs. 6.9% in the clopidogrel group, P=0.005) and death from vascular causes (4.0% vs. 5.1%, P=0.001) but not stroke alone (1.5% vs. 1.3%, P=0.22). The rate of death from any cause was also reduced with ticagrelor (4.5%, vs. 5.9% with clopidogrel; P<0.001). No significant difference in the rates of major bleeding was found between the ticagrelor and clopidogrel groups (11.6% and 11.2%, respectively; P=0.43), but ticagrelor was associated with a higher rate of major bleeding not related to coronary-artery bypass grafting (4.5% vs. 3.8%, P=0.03), including more instances of fatal intracranial bleeding and fewer of fatal bleeding of other types.. In patients who have an acute coronary syndrome with or without ST-segment elevation, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding but with an increase in the rate of non-procedure-related bleeding. (ClinicalTrials.gov number, NCT00391872.)

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Double-Blind Method; Dyspnea; Electrocardiography; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Stroke; Ticagrelor; Ticlopidine

Our goal was to compare the safety and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, with clopidogrel in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS).. AZD6140 achieves higher mean levels of platelet inhibition than clopidogrel in patients with stable coronary artery disease.. A total of 990 patients with NSTE-ACS, treated with aspirin and standard therapy for ACS, were randomized in a 1:1:1 double-blind fashion to receive either twice-daily AZD6140 90 mg, AZD6140 180 mg, or clopidogrel 300-mg loading dose plus 75 mg once daily for up to 12 weeks.. The primary end point, the Kaplan-Meier rate of major or minor bleeding through 4 weeks, was 8.1% in the clopidogrel group, 9.8% in the AZD6140 90-mg group, and 8.0% in the AZD6140 180-mg group (p = 0.43 and p = 0.96, respectively, vs. clopidogrel); the major bleeding rates were 6.9%, 7.1%, and 5.1%, respectively (p = 0.91 and p = 0.35, respectively, vs. clopidogrel). Although not statistically significant, favorable trends were seen in the Kaplan-Meier rates of myocardial infarction (MI) over the entire study period (MI: 5.6%, 3.8%, and 2.5%, respectively; p = 0.41 and p = 0.06, respectively, vs. clopidogrel). In a post-hoc analysis of continuous electrocardiograms, mostly asymptomatic ventricular pauses >2.5 s were more common, especially in the AZD6140 180-mg group (4.3%, 5.5%, and 9.9%, respectively; p = 0.58 and p = 0.01, respectively, vs. clopidogrel).. This initial experience with AZD6140 in patients with ACS showed no difference in major bleeding but an increase in minor bleeding at the higher dose with encouraging results on the secondary end point of MI. This agent is currently being studied in a large outcomes trial in 18,000 patients with ACS.

Topics: Acute Coronary Syndrome; Adenosine; Administration, Oral; Adult; Aged; Aged, 80 and over; Aspirin; Clopidogrel; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Factors; Ticagrelor; Ticlopidine

There is a growing use of ticagrelor in patients undergoing neuroendovascular procedures, especially those who demonstrate clopidogrel resistance. While multiple dosages are studied in the cardiology literature, the optimal dose for patients with neurological pathology has yet to be established. Here, we describe a single center experience involving 39 patients who underwent neuroendovascular procedures that then received an adjusted lower dose of ticagrelor.. A retrospective chart review was performed between 2013 and 2017 for patients on dual anti-platelet therapy (DAPT) for either cervical or intracranial vascular pathologies, as well as stenting of the neurovasculature, including carotid arteries. Patients were placed on ticagrelor if their measured P2Y. The mean number of days for follow-up post treatment initiation was 532 days. A total of 39 patients were included in the analysis. Of these, 8 patients (21%) received implantation of intracranial stents (5 patients received pipeline embolization devices, 1 patient received stent-assisted coiling, and 2 patients received intracranial stents for atherosclerotic disease). Fourteen patients (35%) received carotid angioplasty and stenting. Seventeen patients (44%) did not receive permanent implantation of a stent. All patients on the lower dose ticagrelor of 45 mg twice daily achieved responsiveness (i.e., PRU < 194). Hemorrhagic transformation of ischemic stroke occurred in one patient (2.5%). No other hemorrhagic complications were encountered. No thromboembolic events were recorded aside from one patient (2.5%) with intracranial atherosclerotic disease who had an ischemic event.. A lower dose of ticagrelor (45 mg twice daily) appears to be safe and effective in this small cohort of patients who are resistant to clopidogrel per P2Y

Topics: Clopidogrel; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Retrospective Studies; Ticagrelor; Treatment Outcome

Gene expression biosignatures may hold promise to individualize antiplatelet therapy in conjunction with current guidelines and risk scores. The Aspirin Response Signature (ARS) score is comprised of a weighted sum of correlated, pro-thrombotic gene transcripts measured in whole blood. In prior work where volunteers were exposed to aspirin 325 mg daily, higher ARS score was associated with lower platelet function; separately, in a clinical cohort of patients, higher ARS scores were associated with increased risk of adverse cardiovascular events. To better understand this apparent paradox, we measured ARS gene expression and score in volunteers to determine aspirin dose-response and ticagrelor relationships with ARS score and separately in patients to assess whether ARS is associated with incident bleeding.. Blood samples were collected from volunteers (N = 188) who were exposed to 4 weeks of daily aspirin 81 mg, daily aspirin 325 mg, and/or twice-daily ticagrelor 90 mg. ARS scores were calculated from whole blood RNA qPCR, and platelet function and protein expression were assessed in platelet-rich plasma. In mixed linear regression models, aspirin 81 mg exposure was not associated with changes in ARS gene expression or score. Aspirin 325 mg exposure resulted in a 6.0% increase in ARS gene expression (P = 7.5 × 10-9 vs. baseline, P = 2.1 × 10-4 vs. aspirin 81 mg) and an increase in expression of platelet proteins corresponding to ARS genes. Ticagrelor exposure resulted in a 30.7% increase in ARS gene expression (P < 1 × 10-10 vs. baseline and each aspirin dose) and ARS score (P = 7.0 × 10-7 vs. baseline, P = 3.6 × 10-6 and 5.59 × 10-4 vs. aspirin 81 and 325 mg, respectively). Increases in ARS gene expression or score were associated with the magnitude of platelet inhibition across agents. To assess the association between ARS scores and incident bleeding, ARS scores were calculated in patients undergoing cardiac catheterization (N = 1421), of whom 25.4% experienced bleeding events over a median 6.2 years of follow-up. In a Cox model adjusting for demographics and baseline antithrombotic medication use, patients with ARS scores above the median had a higher risk of incident bleeding [hazard ratio 1.26 (95% CI 1.01-1.56), P = 0.038].. The ARS is an Antiplatelet Response Signature that increases in response to greater platelet inhibition due to antiplatelet therapy and may represent a homeostatic mechanism to prevent bleeding. ARS scores could inform future strategies to prevent bleeding while maintaining antiplatelet therapy's benefit of ischaemic cardiovascular event protection.

Topics: Aspirin; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Ticagrelor; Transcriptome; Treatment Outcome

CYP2C19-guided P2Y12 inhibitor selection can reduce cardiovascular (CV) events and bleeding in patients with acute coronary syndromes (ACSs) post-percutaneous coronary intervention (PCI). The 12-month cost-effectiveness of CYP2C19-guided P2Y12 inhibitor selection for Veterans post-ACS/PCI was evaluated from the Veterans Health Administration's (VHA) perspective.. Using average annualized PCI volumes and P2Y12 inhibitor use from VA data, a decision-analytic model simulated CYP2C19 testing vs. no testing outcomes in 2800 hypothetical Veterans receiving PY212 inhibitor for 12 months post-ACS/PCI (74% clopidogrel, 5% prasugrel, and 21% ticagrelor use at baseline without testing). CYP2C19 loss-of-function (LOF) carrier prevalence was 28%. Model inputs were from studies (bleeding/ischaemic events, CYP2C19-guided therapy effect, health state utilities, CYP2C19 LOF carrier prevalence) and VHA administrative data (costs of events, drugs, CYP2C19 testing; PCI volumes, and P2Y12 inhibitor prescriptions). The primary outcome was cost (2020 US${\\$}$) per quality-adjusted life year (QALY) gained. Base-case scenarios, probabilistic sensitivity analyses, and scenario analyses were completed. CYP2C19-guided therapy resulted in 496 (24%) escalations (clopidogrel to prasugrel/ticagrelor) and 465 (65%) de-escalations (prasugrel/ticagrelor to clopidogrel). CYP2C19 testing averted 1 stroke, 27 myocardial infarctions, 8 CV-related deaths, and caused 3 bleeds. CYP2C19 testing (vs. no testing) was dominant in the base-case scenario (0.0027 QALYs gained, ${\\$}$527 saved/person) and in 97.1% of simulations, making it cost-effective and high-value. In scenario analyses, de-escalation in conjunction with escalation is required for CYP2C19 testing to be cost-effective and high-value.. In Veterans post-ACS/PCI, CYP2C19-guided P2Y12 inhibitor selection can improve CV outcomes and lower costs for the VHA within 12 months of implementation.

Topics: Acute Coronary Syndrome; Clopidogrel; Cost-Benefit Analysis; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C19 Inhibitors; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor; Veterans

The first 3 months after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) is a high-risk period for adverse events, including ischemic and bleeding events, which decrease greatly with time. It is worth investigating whether the use of potent P2Y12 inhibitors is necessary after the early stage. The purpose of this study was to investigate the differences in clinical outcomes between clopidogrel and ticagrelor in stable patients without ischemic or major bleeding events during the first 3 months after PCI.. Data for this study were obtained from the PHARM-ACS registry (NCT04184583). Patients who were free from ischemic and major bleeding events in the first 3 months after PCI were enrolled. Inverse probability of treatment weighting (IPTW) and Cox proportional hazards model were applied to compare the differences in clinical outcomes between the 2 groups. Major adverse cardiovascular and cerebrovascular events (MACCE) were considered the primary end point, and major bleeding was considered the secondary end point.. A total of 6662 patients were included in this study. Of these, 3465 were treated with clopidogrel plus aspirin (clopidogrel group) and 3197 with ticagrelor plus aspirin (ticagrelor group). There were no significant differences in MACCE after IPTW adjustment for baseline variables (IPTW-adjusted HR, 1.06; 95% CI, 0.90-1.25) or major bleeding events (IPTW-adjusted HR, 0.97; 95% CI, 0.67-1.41) between the 2 groups. However, the incidence of minor bleeding in the clopidogrel group was significantly lower than that in the ticagrelor group (IPTW-adjusted HR, 0.65; 95% CI, 0.59-0.71).. In patients with ACS who were free from ischemic or major bleeding events during the first 3 months after PCI, the subsequent clopidogrel treatment might reduce minor bleeding events without increasing the risk of MACCE compared with ticagrelor. However, the results still need to be confirmed by large randomized controlled studies in the future.

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Hemorrhage; Humans; Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Registries; Ticagrelor; Treatment Outcome

In closely monitored randomized controlled trials (RCTs), newer P2Y12 agents (ticagrelor and prasugrel) reduced cardiovascular outcomes compared with clopidogrel following percutaneous coronary intervention (PCI) in acute coronary syndrome. However, these RCTs indicated a higher bleeding risk with these newer agents. This study evaluated the comparative safety of each P2Y12 inhibitor on hospitalizations due to major bleeding in a real-world population. This retrospective, propensity score-matched (PSM) cohort study utilized the IBM MarketScan database over 6 years (2013-2018) to identify incident users of P2Y12 inhibitors with age ≥18 years. The primary safety outcome was hospitalization due to any major bleeding event including gastrointestinal, intracranial, and other serious forms of bleeding. In pairwise comparisons using Cox-proportional hazards models, ticagrelor, prasugrel, and clopidogrel users were compared for the primary safety outcome at 30, 90, and 180 days following the first prescription of P2Y12 inhibitor after PCI. There were 21,719 (ticagrelor vs. clopidogrel), 11,513 (prasugrel vs. clopidogrel), and 11,065 (prasugrel vs. ticagrelor) PSM pairs. Overall, the risk of major bleeding was similar for all P2Y12 inhibitors. Hospitalization for major bleeding was generally lower among ticagrelor users vs. clopidogrel and higher among prasugrel users compared with clopidogrel. Importantly, a 66% higher risk of major bleeding at 90 days is suggested with prasugrel compared with clopidogrel (hazard ratio 1.66; 95% confidence interval, 1.11-2.48). This study indicated a higher short-term bleeding risk with prasugrel compared with clopidogrel, which concurs with the results of RCTs.

Topics: Acute Coronary Syndrome; Adolescent; Clopidogrel; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

During long-term antiplatelet agents (APAs) administration, patients with thrombotic diseases take a fairly high risk of life-threatening bleeding, especially when in need of urgent surgery. Rapid functional reversal of APAs remains an issue yet to be efficiently resolved by far due to the lack of any specific reversal agent in the clinic, which greatly restricts the use of APAs.. Flow cytometry analysis was first applied to assess the dose-dependent reversal activity of platelet-mimicking perfluorocarbon-based nanosponges (PLT-PFCs) toward ticagrelor. The tail bleeding time of mice treated with APAs followed by PLT-PFCs was recorded at different time points, along with corresponding pharmacokinetic analysis of ticagrelor and tirofiban. A hemorrhagic transformation model was established in experimental stroke mice with thrombolytic/antiplatelet therapy. Magnetic resonance imaging was subsequently applied to observe hemorrhage and thrombosis in vivo. Further evaluation of the spontaneous clot formation activity of PLT-PFCs was achieved by clot retraction assay in vitro.. PLT-PFCs potently reversed the antiplatelet effect of APAs by competitively binding with APAs. PLT-PFCs showed high binding affinity comparable to fresh platelets in vitro with first-line APAs, ticagrelor and tirofiban, and efficiently reversed their function in both tail bleeding and postischemic-reperfusion models. Moreover, the deficiency of platelet intrinsic thrombotic activity diminished the risk of thrombogenesis.. This study demonstrated the safety and effectiveness of platelet-mimicking nanosponges in ameliorating the bleeding risk of different APAs, which offers a promising strategy for the management of bleeding complications induced by antiplatelet therapy.

Topics: Animals; Blood Platelets; Hemorrhage; Mice; Platelet Aggregation Inhibitors; Thrombosis; Ticagrelor; Tirofiban

Antiplatelet therapy (APT) is a key element limiting the risk of thromboembolic events (TEE) in neuroendovascular procedures, including aneurysm treatment with flowdiverter. Clopidogrel combined with aspirin is the mostly reported dual APT (DAPT). However, resistance phenomenon and intraindividual efficacy fluctuation are identified limitations. In recent years, ticagrelor has been increasingly used in this indication. We compared these two DAPT regimens for intracranial aneurysm treated with flowdiverter.. We conducted a multicentric retrospective study from prospectively maintained databases in two high volume centers extracting consecutive patients presenting unruptured intracranial aneurysm treated with flowdiverter and receiving DAPT (May 2015 to December 2019).  Two groups were compared according to their DAPT regimen: "ticagrelor+aspirin" and "clopidogrel+aspirin". Clopidogrel group was systematically checked with platelet test inhibition before endovascular procedure. The primary endpoint was composite, defined as any thrombo-embolic event (TEE) or major hemorrhagic event occurring the first 6 months during and after embolization RESULTS: 260 patients met our inclusion criteria. Baseline patients and aneurysms characteristics were comparable between groups, except for aneurysm location, median size and pre-treatment modified Rankin scale. No significant difference was observed regarding the primary composite outcome: 11.5% (12/104) in the ticagrelor group versus 10.9% (17/156) in the clopidogrel group (p = 1.000). There was also no significant difference in secondary outcomes including TEE (10.5 vs 9.0%; p = 0.673), major hemorrhage (0.9 vs 1.2%; p = 0.651) and clinical outcome (at least 1-point mRS worsening during follow up: 6.7% vs 8.3%; p = 0.813).. First-line DAPT with ticagrelor+aspirin seems as safe and effective as clopidogrel+aspirin regimen.

Topics: Aspirin; Clopidogrel; Hemorrhage; Humans; Intracranial Aneurysm; Platelet Aggregation Inhibitors; Retrospective Studies; Thromboembolism; Ticagrelor; Treatment Outcome

Potent P2Y. We sought to compare the safety and efficacy of prasugrel and ticagrelor versus clopidogrel in patients undergoing PCI for CCS.. Consecutive patients undergoing PCI for CCS at a tertiary centre between 2014 and 2019 who were discharged on prasugrel or ticagrelor were compared with those on clopidogrel. The primary endpoint was the composite of death and myocardial infarction (MI), with secondary outcomes including rates of bleeding, stroke, and target vessel revascularisation at 1 year.. Ticagrelor and prasugrel are increasingly used in patients with CCS undergoing PCI with similar 1-year efficacy and safety when compared to clopidogrel. Whether use of these agents can be beneficial in patients undergoing PCI for CCS with a high thrombotic and low bleeding risk warrants further study.

Topics: Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

Early P2Y. In this single-arm pilot study, we evaluated the feasibility and safety of ticagrelor or prasugrel monotherapy directly following PCI in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS).. Patients received a loading dose of ticagrelor or prasugrel before undergoing platelet function testing and subsequent PCI using new-generation drug-eluting stents. The stent result was adjudicated with optical coherence tomography in the first 35 patients. Ticagrelor or prasugrel monotherapy was continued for 12 months. The primary ischaemic endpoint was the composite of all-cause mortality, myocardial infarction, definite or probable stent thrombosis or stroke within 6 months. The primary bleeding endpoint was Bleeding Academic Research Consortium type 2, 3 or 5 bleeding within 6 months.. From March 2021 to March 2022, 125 patients were enrolled, of whom 75 ultimately met all in- and exclusion criteria (mean age 64.5 years, 29.3% women). Overall, 70 out of 75 (93.3%) patients were treated with ticagrelor or prasugrel monotherapy directly following PCI. The primary ischaemic endpoint occurred in 3 (4.0%) patients within 6 months. No cases of stent thrombosis or spontaneous myocardial infarction occurred. The primary bleeding endpoint occurred in 7 (9.3%) patients within 6 months.. This study provides first-in-human evidence that P2Y

Topics: Acute Coronary Syndrome; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Pilot Projects; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor; Treatment Outcome

Excess mortality remains the cornerstone concern despite dual antiplatelet therapy (DAPT) after acute coronary syndrome. Some data suggest that shorter periods than 12 months of DAPT diminish bleeding risks yet still provide adequate vascular protection and improving survival. However, the precise timing of deaths after acute coronary syndrome has not been mapped in many studies. This knowledge may be critical for defining optimal treatment duration.. Access was gained to the data set for the Platelet Inhibition and Outcomes (PLATO) trial, which was issued by the Food and Drug Administration, in which post hoc analyses of timing of death events during DAPT (with either aspirin/ticagrelor or aspirin/clopidogrel) were performed. All-cause individual deaths were counted and plotted over time from day 1 to day 365 after the index event.. Among 18,624 enrollees, 938 total deaths were reported to the Food and Drug Administration in PLATO. After exclusion of deceased patients with missing dates, randomization errors, and deaths beyond 1 year of follow-up, 913 fatalities (509 after clopidogrel and 404 after ticagrelor) were analyzed. The PLATO records did not indicate where exactly deaths occurred making impossible to triage in the hospital versus outpatient fatalities. Most frequent deaths occurred within the Day 1 (n = 41); Day 2 (n = 48); and Day 3 (n = 33) and overall during the first week (n = 202; 22.1%) after the index acute coronary syndrome, with a gradual decline after Day 10 and Day 60, reaching background counts after Day 220.. Focusing on mortality reduction, this large data set may support a shorter than 12 months' duration of DAPT.

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Ticlopidine; Treatment Outcome

To appraise all available antithrombotic treatments within or after 12 months following coronary revascularization and/or acute coronary syndrome in two network meta-analyses.. Forty-three (N = 189 261 patients) trials within 12 months and 19 (N = 139 086 patients) trials beyond 12 months were included for efficacy/safety endpoints appraisal. Within 12 months, ticagrelor 90 mg bis in die (b.i.d.) [hazard ratio (HR), 0.66; 95% confidence interval (CI), 0.49-0.88], aspirin and ticagrelor 90 mg (HR, 0.85; 95% CI, 0.76-0.95), or aspirin, clopidogrel and rivaroxaban 2.5 mg b.i.d. (HR, 0.66; 95% CI, 0.51-0.86) were the only treatments associated with lower cardiovascular mortality, compared with aspirin and clopidogrel, without or with greater bleeding risk for the first and the other treatment options, respectively. Beyond 12 months, no strategy lowered mortality; compared with aspirin; the greatest reductions of myocardial infarction (MI) were found with aspirin and clopidogrel (HR, 0.68; 95% CI, 0.55-0.85) or P2Y12 inhibitor monotherapy (HR, 0.76; 95% CI: 0.61-0.95), especially ticagrelor 90 mg (HR, 0.54; 95% CI, 0.32-0.92), and of stroke with VKA (HR, 0.56; 95% CI, 0.44-0.76) or aspirin and rivaroxaban 2.5 mg (HR, 0.58; 95% CI, 0.44-0.76). All treatments increased bleeding except P2Y12 monotherapy, compared with aspirin.. Within 12 months, ticagrelor 90 mg monotherapy was the only treatment associated with lower mortality, without bleeding risk trade-off compared with aspirin and clopidogrel. Beyond 12 months, P2Y12 monotherapy, especially ticagrelor 90 mg, was associated with lower MI without bleeding trade-off; aspirin and rivaroxaban 2.5 mg most effectively reduced stroke, with a more acceptable bleeding risk than VKA, compared with aspirin.Registration URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifiers: CRD42021243985 and CRD42021252398.

Topics: Aspirin; Cardiology; Clopidogrel; Coronary Artery Disease; Fibrinolytic Agents; Hemorrhage; Humans; Myocardial Infarction; Network Meta-Analysis; Purinergic P2Y Receptor Antagonists; Rivaroxaban; Stroke; Ticagrelor

To investigate the effectiveness of de-escalation of ticagrelor (from ticagrelor 90 mg to clopidogrel 75 mg or ticagrelor 60 mg) on the prognosis of patients with ST segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) after 3 months of oral dual antiplatelet therapy (DAPT).. From March 2017 to August 2021, 1056 patients with STEMI in a single centre, through retrospective investigation and analysis, were divided into intensive (ticagrelor 90 mg), standard (clopidogrel 75 mg after PCI) and de-escalation groups (clopidogrel 75 mg or ticagrelor 60 mg after 3 months of treatment with 90 mg ticagrelor) based on the type and dose of P2Y. The results showed that during the follow-up period, there was no statistically significant difference in the incidence of MACCEs between the intensive and de-escalation groups (P > 0.05). The incidence of MACCEs in the standard treatment group was higher than that in the intensive treatment group (P = 0.014), but the incidence of bleeding events in the de-escalation group was significantly lower than that in the standard group (9.3% vs. 18.4%, χ²=7.191, P = 0.027). The Cox regression analysis showed that increases in haemoglobin (HGB) (HR = 0.986) and estimated glomerular filtration rate (eGFR) (HR = 0.983) could reduce the incidence of MACCEs, while old myocardial infarction (OMI) (P = 0.023) and hypertension (P = 0.013) were independent predictors of MACCEs.. For STEMI patients undergoing PCI, the de-escalation scheme of ticagrelor to clopidogrel 75 mg or ticagrelor 60 mg at 3 months after PCI was related to the reduction of bleeding events, especially minor bleeding events, without an increase in ischaemic events.

Topics: Clopidogrel; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prognosis; Retrospective Studies; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

This study was conducted to compare the efficacy and safety of ticagrelor and clopidogrel in patients with acute coronary syndrome (ACS) treated with primary percutaneous coronary intervention (PPCI). A total of 3528 consecutive patients with ACS treated with PPCI were divided into the ticagrelor and clopidogrel groups based on their dual antiplatelet therapy regimen at hospital discharge. Patient follow-up visits were completed 1, 6, and 12 months after PPCI treatment. Major adverse cardiac events (MACEs) and Bleeding Academic Research Consortium (BARC) bleeding events were assessed in both groups. In total, 2501 cases were included in the ticagrelor group, and 817 cases were included in the clopidogrel group. The incidence of MACEs was lower in the ticagrelor group than in the clopidogrel group (P < .05). The ticagrelor group had lower incidence of all-cause death and cardiac death compared with the clopidogrel group, and the difference was significant (P < .05). The incidences of study end points, including recurrent myocardial infarction and repeat revascularization, were not significantly different between the groups (P > .05). The incidences of BARC total and major bleeding events were not significantly different between the groups (P > .05). However, the incidences of BARC type 1 and 2 bleeding events were lower in the ticagrelor group than in the clopidogrel group (P < .05). The multivariate Cox regression analysis suggested that ticagrelor could decrease all-cause death compared with clopidogrel (P = .021). In patients with ACS treated with PPCI, ticagrelor could significantly reduce the risk of MACEs compared with clopidogrel, without increasing the risk of bleeding.

Topics: Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

A platelet ADP P2Y12 receptor (P2Y12) inhibitor plus aspirin is standard therapy for patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Compared with clopidogrel, prasugrel and ticagrelor are associated with superior antiatherothrombotic effects but increased bleeding risk; with recent guideline updates, it is important to describe current treatment patterns and the role of bleeding risk in treatment choice.. To describe secular trends and determinants of initial P2Y12 inhibitor choice and switching, including deescalation (switch from prasugrel or ticagrelor to clopidogrel).. This retrospective cohort study used MarketScan Commercial Claims Data from 2010 to 2019 for patients aged 18 years or older who underwent PCI for ACS, had no P2Y12 inhibitor use in the past year, and filled a P2Y12 inhibitor prescription within 30 days after PCI hospitalization discharge. Data were analyzed from February to May 2022.. Clopidogrel, prasugrel, and ticagrelor, with determinants including bleeding risk measured using Academic Research Consortium for High Bleeding Risk criteria, sociodemographic characteristics, P2Y12 inhibitor copays, and bleeding events during follow-up.. The prevalence of each P2Y12 inhibitor among patients who initiated the drugs and the prevalence of switching within 12 months after PCI were evaluated. The association between baseline bleeding risk and bleeding manifestations during follow-up and initial treatment and deescalation were calculated using multivariable logistic and Cox proportional hazards regression models.. Between 2010 and 2019, 62 423 patients were identified who initiated P2Y12 inhibitors (females, 22.4%; males, 77.6%; mean [SD] age, 54.32 [7.13] years). The prevalence of clopidogrel as initial therapy decreased from 77.5% in 2010 to 29.6% in 2019, while initial use of prasugrel or ticagrelor increased from 22.5% to 60.4%. Within 1 year after PCI, 11.0% of patients switched therapy, mostly for deescalation. Deescalation prevalence increased from 1.8% in 2010 to 12.6% in 2018. Between 2016 and 2018, 8588 of 22 886 (37.5%) patients had major baseline bleeding risk, which decreased the selection of prasugrel or ticagrelor as initial therapy (adjusted odds ratio, 0.78; 95% CI, 0.74-0.84). Among 11 285 patients who initiated prasugrel or ticagrelor, major bleeding risk at baseline (adjusted hazard ratio, 1.11; 95% CI, 1.00-1.23) and the occurrence of bleeding during follow-up (adjusted hazard ratio, 4.42; 95% CI, 3.62-5.93) were associated with deescalation.. A strong shift in preference for prasugrel and ticagrelor as initial therapy following PCI for ACS was observed. Deescalation increased over the study period. Major bleeding risk at baseline was moderately associated with initial treatment choice but had a limited association with deescalation. The increasing use of more potent P2Y12 inhibitors emphasizes opportunities to enhance preemptive patient-centered treatment strategies to maintain optimal antiplatelet activity while reducing bleeding risk during the subacute period following PCI for ACS.

Topics: Acute Coronary Syndrome; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Retrospective Studies; Ticagrelor

The TWILIGHT trial (NCT02270242) demonstrated that in selected high-risk patients undergoing percutaneous coronary intervention (PCI) ticagrelor monotherapy significantly reduced bleeding complications without ischemic harm as compared to ticagrelor plus aspirin after 3-month of dual antiplatelet therapy. The aim of this analysis was to assess the applicability of the findings TWILIGHT trial to a real-world population.. Patients undergoing PCI at a tertiary center between 2012 and 2019 and not meeting any TWILIGHT exclusion criterion (oral anticoagulation treatment, ST-segment elevation myocardial infarction [MI], cardiogenic shock, dialysis, prior stroke, or thrombocytopenia) were included. Patients were stratified into 2 groups based on whether they fulfilled the TWILIGHT inclusion criteria (high-risk) or not (low-risk). The primary outcome was all-cause death; the key secondary outcomes were MI and major bleeding at 1 year after PCI.. Out of 13,136 included patients, 11,018 (83%) were at high risk. At 1-year, these patients had an approximately 3 folds greater hazard of death (1.4% vs 0.4%, HR 3.63, 95% CI 1.70-7.77) and MI (1.8% vs 0.6%, HR 2.81, 95% CI 1.56-5.04) and a nearly 2 folds higher risk of major bleeding (3.3% vs 1.8%, HR 1.86, 95% CI 1.32-2.62) as compared to low-risk patients.. Among patients not meeting the TWILIGHT exclusion criteria from a large PCI registry, the high-risk inclusion criteria of the TWILIGHT trial were met by the majority of patients and were associated with an increased risk of mortality and MI and a moderately elevated risk of bleeding.

Topics: Drug Therapy, Combination; Hemorrhage; Humans; Patient Selection; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Registries; Ticagrelor; Treatment Outcome

Topics: Acute Coronary Syndrome; Cytochrome P-450 CYP3A; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Dual antiplatelet therapy with acetylsalicylic acid and a P2Y12 inhibitor has become a mainstay of therapy after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Although higher-potency P2Y12 inhibitors are preferred over clopidogrel in major society guidelines, recent evidence has questioned the extent of the benefit. It is important to evaluate the relative efficacy and safety of P2Y12 inhibitors in a real-world setting. This is a retrospective cohort study of all patients who underwent PCI for ACS in a Canadian province from January 1, 2015 to March 31, 2020. Baseline characteristics, including co-morbidities, medications, and bleeding risk, were obtained. Propensity matching was used to compare patients who received ticagrelor versus clopidogrel. The primary outcome was occurrence of major adverse cardiovascular events (MACEs) at 12 months, defined as death, nonfatal myocardial infarction, or unplanned revascularization. Secondary outcomes included all-cause mortality, major bleeding, stroke, and all-cause hospitalization. A total of 6,665 patients were included; 2,108 received clopidogrel and 4,214 received ticagrelor. Patients who received clopidogrel were older, had more co-morbidities, including cardiovascular risk factors, and had a higher bleeding risk. In 1.925 propensity score-matched pairs, ticagrelor was associated with a significantly lower risk of MACE (hazard ratio 0.79, 0.67 to 0.93, p <0.01) and hospitalization (hazard ratio 0.85, 0.77 to 0.95, p <0.01). No difference was observed in the risk of major bleeding. A statistically nonsignificant trend toward reduced risk of all-cause mortality was noted. In conclusion, in a real-world high-risk cohort, ticagrelor was associated with decreased risk of MACE and all-cause hospitalization compared with clopidogrel after PCI for ACS.

Topics: Acute Coronary Syndrome; Canada; Clopidogrel; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Ticagrelor; Treatment Outcome

Antithrombotic drugs, including the P2Y. We used a Markov model to analyze the cost-effectiveness and budget impact of the hemoadsorption device in three cohorts: (1) surgery within 1 day from last ticagrelor dose; (2) surgery between 1 and 2 days from last ticagrelor dose; and (3) a combined cohort. The model analyzed costs and quality-adjusted life years (QALYs). Results were interpreted as both incremental cost-effectiveness ratios and net monetary benefits (NMBs) at a cost-effectiveness threshold of $100,000/QALY. We analyzed parameter uncertainty using deterministic and probabilistic sensitivity analyses.. The hemoadsorption device was dominant for each cohort. Patients with less than 1 day of washout in the device arm gained 0.017 QALYs at a savings of $1748 (USD), for an NMB of $3434. In patients with 1-2 days of washout, the device arm yielded 0.014 QALYs and a cost savings of $151, for an NMB of $1575. In the combined cohort, device gained 0.016 QALYs and a savings of $950 for an NMB of $2505. Per-member-per-month cost savings associated with device was estimated to be $0.02 for a one-million-member health plan.. This model found the hemoadsorption device to provide better clinical and economic outcomes compared with the standard of care in patients who required surgery within 2 days of ticagrelor discontinuation. Given the increasing use of ticagrelor in patients with acute coronary syndrome, incorporating this novel device may represent an important part of any bundle to save costs and reduce harm.

Topics: Acute Coronary Syndrome; Coronary Artery Bypass; Cost-Benefit Analysis; Fibrinolytic Agents; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Ticagrelor

It remains controversial whether to extend the course of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). We conducted a study to investigate the benefits and risks of applying DAPT for different durations after PCI in acute coronary syndromes (ACS) patients in China. What's more, we explored the efficacy of extended DAPT regimen based on ticagrelor.. This single-center prospective cohort study used data obtained from the PHARM-ACS Patient Registration Database. We included all patients who were discharged between April and December 2018. All patients had at least 18 months of follow-up. Patients were divided into two groups according to the duration of DAPT: a 1-year group and a >1-year group. Potential bias between the two groups was adjusted for by propensity score matching using logistic regression. The primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE), defined as a composite of death, myocardial infarction, and stroke occurring from 12 months after discharge to follow-up visit. The safety endpoint was any significant bleeding event (BARC ≥ 2).. Of 3,205 patients enrolled, 2,201 (68.67%) had DAPT prolonged beyond one year. A total of 2,000 patients were successfully propensity score-matched; patients who received DAPT > 1-year (n = 1000), compared with DAPT = 1-year patients (n = 1000), had a similar risk of MACCE (adjusted HR 0.23, 95% CI 0.05-1.10) and significant bleeding events (adjusted HR 0.63, 95% CI 0.32-1.24). The DAPT > 1-year group had a higher risk of revascularization (adjusted HR 3.36, 95% CI 1.64-6.87).. Prolonged DAPT may not be of sufficient benefit to ACS patients within 12-18 months after the index PCI to offset the increased risk of significant bleeding events.

Topics: Acute Coronary Syndrome; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Ticagrelor; Treatment Outcome

Randomized trials have shown superiority of the novel P2Y12 inhibitors over clopidogrel in patients with acute coronary syndrome (ACS), but clinical benefit in the community remains controversial. Our objective was to compare the safety and efficacy of clopidogrel to ticagrelor and prasugrel in patients with ACS undergoing percutaneous coronary intervention (PCI) in a real-world population.. We conducted a retrospective cohort study of patients with ACS who underwent PCI and were discharged with clopidogrel, ticagrelor, or prasugrel from 2012 to 2018 within Kaiser Permanente Northern California. We used Cox proportional hazard models with propensity-score matching to evaluate the association of the P2Y12 agent with the primary outcomes of all-cause mortality, myocardial infarction (MI), stroke, and bleeding events.. The study included 15,476 patients (93.1% on clopidogrel, 3.6% on ticagrelor and 3.2% on prasugrel). Compared to the clopidogrel group, ticagrelorand prasugrel patients were younger with less comorbidities. In multivariable models with propensity-score matching, we found a lower risk of all-cause mortality in the ticagrelor vs the clopidogrel group (HR (95% CI) 0.43 (0.20-0.92)), but no differences in the other endpoints, and no difference between prasugrel and clopidogrel among any endpoints. A larger proportion of patients on ticagrelor or prasugrel switched to an alternative P2Y12 agent vs. clopidogrel (. Among patients with ACS who underwent PCI, we observed a lower risk of all-cause mortality in patients treated with ticagrelor vs clopidogrel, but no difference in other clinical endpoints nor any differences in endpoints between prasugrel vs. clopidogrel users. These results suggest that further study is needed to identify an optimal P2Y12 inhibitor in a real-world population.

Topics: Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Humans; Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Ticagrelor; Treatment Outcome

Ticagrelor is associated with a lower risk of ischemic events than clopidogrel. However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in patients who have a high bleeding risk (HBR). Therefore, this study compared ticagrelor and clopidogrel in myocardial infarction (MI) patients with HBR.. This study included all patients enrolled in the SWEDEHEART registry who were discharged with dual antiplatelet therapy using ticagrelor or clopidogrel following MI between 2010 and 2017. High bleeding risk was defined as a PRECISE-DAPT score ≥25. Information on ischemic events, major bleeding, and mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and bleeding. This study included 25 042 HBR patients, of whom 11 848 were treated with ticagrelor. Ticagrelor was associated with a lower risk of MI, stroke, and MACE, but a higher risk of bleeding compared to clopidogrel. There were no significant differences in mortality and NACE. Additionally, when examining the relationship between antiplatelet therapy and bleeding risk in 69 040 MI patients, we found no statistically significant interactions between the PRECISE-DAPT score and treatment effect.. We observed no difference in NACE when comparing ticagrelor and clopidogrel in HBR patients. Moreover, we found no statistically significant interactions between bleeding risk and the comparative effectiveness of clopidogrel and ticagrelor in a larger population of MI patients.

Topics: Clopidogrel; Hemorrhage; Humans; Ischemia; Myocardial Infarction; Platelet Aggregation Inhibitors; Stroke; Ticagrelor

Nuisance bleeding (NB) without urgent medical attention is rarely characterized despite its frequent occurrence in patients with cerebral aneurysms undergoing flow diversion (FD) who are maintained on dual antiplatelet therapy (DAPT). This study explored the risk factors for NB. Patients with unruptured cerebral aneurysms who underwent intervention using FD (July 2018 to May 2022) and had follow-up data were enrolled. Patient demographics, clinical characteristics, aneurysm features and follow-up data were analysed. Bleeding complications were classified as NB, internal bleeding and alarming bleeding. NB was characterized by easy bruising, bleeding from small cuts and nonfatal petechiae and ecchymosis. Univariate and multivariate logistic regression analyses were performed to determine risk factors for NB. This study assessed 121 patients. Of these, 52 (43.0%) patients had NB. Compared with the non-bleeding group, the NB group had more females (82.7% vs. 56.5%; p = 0.003), lower smoking rate (7.7% vs. 23.2%; p = 0.027) and smaller aneurysms (6.65 mm [4.60-9.60 mm] vs. 8.82 mm [5.65-15.65 mm]; p = 0.007) and had more patients maintained on ticagrelor-containing DAPT regimen (90.4% vs. 66.7%; p = 0.002). Multivariate logistic regression revealed that ticagrelor-containing DAPT regimen (odds ratio, 3.91; 95% confidence interval, 1.29-11.87; p = 0.016) was associated with NB. These results suggest that NB is a common bleeding complaint in patients on DAPT. In patients undergoing FD, DAPT with ticagrelor was the only independent risk factor for NB.

Topics: Female; Hemorrhage; Humans; Intracranial Aneurysm; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor; Treatment Outcome

This study evaluated the association among the plasma concentration of ticagrelor, ARC124910XX, aspirin, and salicylic acid with the risk of recent bleeding in patients with the acute coronary syndrome. To this end, we developed an accurate model to predict bleeding.. A total of 84 patients included in this study cohort between May 2021 and November 2021. The risk factors were identified by univariate and multivariate analyses, and statistically significant risk factors identified in the multivariate analysis were included in the nomogram. We used the calibration curve and the receiver operating characteristic curve to verify the accuracy of the prediction model.. Multivariable logistic analysis showed that ticagrelor concentration (odds ratio [OR]: 2.47, 95% confidence interval [CI], 1.51-4.75, P = 0.002), ST-segment elevation acute myocardial infarction (OR: 32.2, 95% CI, 2.37-780, P = 0.016), and lipid-lowering drugs (OR: 11.52, 95% CI, 1.91-110, P = 0.015) were positively correlated with bleeding. However, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (OR: 0.04, 95% CI, 0.004-0.213, P < 0.001) was negatively correlated with bleeding. The receiver operating characteristic curve analysis showed that ticagrelor concentration and these factors together predict the occurrence of bleeding (area under receiver operating characteristic curve = 0.945, 95% CI, 0.896-0.994) and that ticagrelor concentration >694.90 ng/mL is the threshold of bleeding concentration (area under receiver operating characteristic curve = 0.696, 95% CI, 0.558-0.834).. In patients with acute coronary syndrome treated with dual antiplatelet therapy, ticagrelor concentration >694.90 ng/mL was an independent risk factor for bleeding (OR: 2.47, 95% CI, 1.51-4.75, P = 0.002), but ARC124910XX and salicylic acid concentration did not affect bleeding risk ( P > 0.05).

Topics: Acute Coronary Syndrome; Aspirin; East Asian People; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Salicylic Acid; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

There has been an increase in the number of percutaneous coronary intervention (PCI) procedures performed in octogenarian patients due to increased life expectancy and developments in modern medicine. Frailty is associated with the aging process, gradual loss of multiple body functions, and poor health outcomes. We examined the association between frailty and major bleeding in octogenarian patients undergoing PCI.. We retrospectively analyzed the records of two local research hospitals in Turkey. In total, 244 patients were enrolled in this study. Patients were divided into two groups based on their Clinical Frailty Scale (CFS) score. The non-frail group included patients with CFS scores of 1 (very fit) to 4 (living with very mild frailty), while the frail group included those with CFS scores of 5 (living with mild frailty) to 9 (terminally ill).. Of the 244 patients, 131 were classified into the non-frail group and 113 into the frail group. Ticagrelor use was significantly more common in the non-frail group (31.3% vs. 20.4%, p=0.036). Major bleeding was more common in the frail than non-frail group (20.4% vs. 6.1%, p<0.001). The rates of stroke and all-cause death were higher in the frail than in non-frail group (stroke 15.9% vs. 3.8%, p<0.001, as well as all-cause mortality rate (27.4% vs. 2.3%, p<0.001).. Frailty is an independent predictor of major bleeding in patients undergoing PCI for acute coronary syndrome. Use of the P2Y12 inhibitor ticagrelor increases the risk of major bleeding in frail patients.

Topics: Aged, 80 and over; Frailty; Hemorrhage; Humans; Octogenarians; Percutaneous Coronary Intervention; Retrospective Studies; Stroke; Ticagrelor

As a part of dual antiplatelet therapy (DAPT), prasugrel or ticagrelor is prescribed along with aspirin to patients of acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We aimed to assess if the PRECISE-DAPT score, which provides prediction of bleeding during DAPT, could be used to choose between prasugrel and ticagrelor for DAPT initiation. 181 patients out of which 71 received prasugrel and 110 received ticagrelor were enrolled in this prospective cohort study. PRECISE-DAPT score was calculated for everyone and was used to dichotomize patients into two subgroups (score <25 and ≥25). After balancing potential confounders in baseline characteristics of the subgroups using propensity scores, comparison of a composite outcome of 4-point major adverse cardiovascular events (4P-MACE) (i.e., cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization due to stent thrombosis) and bleeding (any type as defined by the Bleeding Academic Research Consortium) within 1-year post-PCI was performed among the subgroups using Cox proportional hazards regression. Prasugrel was associated with lower and comparatively higher 4P-MACE events in subgroups with score ≥25 (HR: 0.17; 95% CI, 0.04-0.77) and score <25 (HR: 3.58; 95% CI, 0.62-20.70) respectively. For bleeding outcome, prasugrel trended towards more clinical benefit for scores ≥25 (HR: 0.44; 95% CI, 0.10-1.93) than <25 (HR: 0.93; 95% CI, 0.13-6.58). Therefore, prasugrel was associated with better clinical effectiveness and trended towards a lower bleeding risk compared to ticagrelor within 1-year post-PCI for those with a high PRECISE-DAPT score (≥25). This finding requires validation through larger studies.

Topics: Acute Coronary Syndrome; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Ticagrelor; Treatment Outcome

To characterize and follow patients with ST-segment elevation myocardial infarction (STEMI) at high bleeding risk (HBR) according to the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score, and to examine the use of P2Y12 inhibitors and the subsequent risk of major adverse cardiovascular events (MACE) and bleeding.. This single-centre cohort study included 6179 consecutive STEMI patients who underwent percutaneous coronary intervention (PCI) at Copenhagen University Hospital, Rigshospitalet, between 2009 and 2016. Individual linkage to nationwide registries was conducted to obtain information on diagnoses, claimed drugs, and vital status. Of the 5532 (89.5%) patients with available PRECISE-DAPT scores, 33.0% were at HBR and more often elderly and female with more comorbidities than non-HBR patients. One-year cumulative incidence rates per 100 person-years were 8.7 and 2.1 for major bleeding and 36.8 and 8.3 for MACE in HBR and non-HBR patients, respectively. Among the 4749 (85.8%) patients who survived and collected a P2Y12 inhibitor ≤7 days from discharge, 68.2% of HBR patients were treated with ticagrelor or prasugrel and 31.8% with clopidogrel, while 18.2% non-HBR patients were treated with clopidogrel. Adherence was high for all (>75% days coverage). The risk of MACE was lower in ticagrelor- and prasugrel-treated patients than in clopidogrel-treated patients without differences in major bleeding.. One-third of PCI-treated all-comer patients with STEMI were at HBR according to the PRECISE-DAPT score and were more often treated with potent P2Y12 inhibitors instead of clopidogrel. Thus, ischaemic risk may be weighted over bleeding risk in STEMI patients at HBR.

Topics: Aged; Clopidogrel; Cohort Studies; Female; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; ST Elevation Myocardial Infarction; Ticagrelor

To investigate the effect of different DAPTs in patients with ACS undergoing PCI, and to identify the most efficient DAPT to reduce the risk of ischemia and bleeding after PCI. Between March 2017 and December 2021, 1598 patients with ACS who underwent PCI were included in the study. The DAPT protocol included the clopidogrel group (aspirin 100 mg + clopidogrel 75 mg), ticagrelor group (aspirin 100 mg + ticagrelor 90 mg), de-escalation Group 1 (reduced dose of ticagrelor [from 90 mg to 60 mg]) after 3 months of oral DAPT [aspirin 100 mg + ticagrelor 90 mg]), and de-escalation Group 2 (switched from ticagrelor to clopidogrel after 3 months of oral DAPT [aspirin 100 mg + ticagrelor 90 mg]). All patients received a 12-month follow-up. The primary endpoint was net adverse clinical events (NACEs) that included the composite endpoints of cardiac death, myocardial infarction, ischemia-driven revascularization, stroke, and bleeding events. There were 2 secondary endpoints, major adverse cardiovascular and cerebrovascular events (MACCEs) and bleeding. No statistically significant difference was found in the incidence of NACEs between the 4 groups at the average 12-month follow-up (15.7% vs 19.2% vs 16.7% vs 20.4%). Cox regression analysis revealed that DAPT ticagrelor group regimen (hazard ratio [HR] 0.547; 95% confidence interval [CI]: 0.334-0.896; P  = .017) were associated with a lower risk of MACCEs. Age (HR 1.024; 95% CI: 1.003-1.046; P  = .022). DAPT de-escalation Group 2 regimen (HR 1.665; 95% CI: 1.001-2.767; P  = .049) were marginally associated with a higher risk of MACCEs. Ticagrelor group regimen (HR 1.856; 95% CI: 1.376-2.504; P  < .001) was associated with higher risk of bleeding events. Ticagrelor group regimen (HR 1.606; 95% CI: 1.179-2.187; P  = .003) were associated with a higher risk of minor bleeding events. For patients with ACS underwent PCI, there were no significant difference in the incidence of NACEs between 3 and 12 months after PCI between de-escalation and non-de-escalation therapies. Compared with ticagrelor-based 12-month DAPT, there was no significant difference in MACCEs and bleeding events in patients receiving de-escalation treatment (ticagrelor reduction from 90 to 60 mg, 3 months after PCI).

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Hemorrhage; Humans; Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

To evaluate potential gains in outcomes from ticagrelor-based strategy according to risk stratification by Global Registry of Acute Coronary Events (GRACE) score.. A total of 19,704 patients discharged alive post-acute coronary syndrome who underwent percutaneous coronary intervention and received ticagrelor or clopidogrel between March 2016 and March 2019 were included in the study. The primary endpoint was ischemic events at 12 months, composed of cardiac death, myocardial infarction, and/or stroke. Secondary outcomes included all-cause mortality and Bleeding Academic Research Consortium type 2 to 5 and 3 to 5 bleeding.. The ticagrelor group comprised 6432 (32.6%) patients and the clopidogrel group comprised 13,272 (67.4%) patients. During the follow-up period, there was a significant reduction in the incidence of ischemic events in patients treated using ticagrelor who had excessive risk of bleeding. According to the GRACE score, among low-risk patients, ticagrelor use compared with clopidogrel was not associated with decreased ischemic events (HR, 0.82; 95% CI, 0.57 to 1.17; P=.27) with excessive risk of Bleeding Academic Research Consortium type 3 to 5 bleeding (HR, 1.59; 95% CI, 1.16 to 2.17; P=.004). The risk of ischemic events (HR, 0.60; 95% CI, 0.41 to 0.89; P=.01) were lower in the intermediate- to high-risk patients treated with ticagrelor without significant difference in BARC type 3 to 5 bleeding risk (HR, 1.11; 95% CI, 0.75 to 1.65; P=.61).. There was still a gap between guideline-indicated therapy and the clinical practice in a sizable subset of patients with acute coronary syndrome who underwent percutaneous coronary intervention. The GRACE risk score could identify patients who would derive benefit from the ticagrelor-based antiplatelet strategy.

Topics: Acute Coronary Syndrome; China; Clopidogrel; Hemorrhage; Humans; Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Registries; Risk Assessment; Risk Factors; Ticagrelor; Treatment Outcome

It is unclear whether patients with different stroke/transient ischemic attack etiologies benefit differently from gene-directed dual antiplatelet therapy. This study explored the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in transient ischemic attack or minor stroke with different causes in the CHANCE-2 trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II).. This was a prespecified analysis of the CHANCE-2 trial, which enrolled 6412 patients with minor stroke or transient ischemic attack who carried. A total of 6336 patients were included in this study. In patients administered ticagrelor-aspirin and clopidogrel-aspirin, respectively, stroke recurred in 85 (9.8%) and 88 (10.7%) patients with large-artery atherosclerosis (hazard ratio, 0.86 [95% CI, 0.63-1.18];. In this prespecified analysis of the CHANCE-2 trial, the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing new stroke were consistent in patients with different causes. The influence of stroke cause on benefit of gene-guided antiplatelet therapy should be explored by further trials.. URL: https://www.. gov; Unique identifier: NCT04078737.

Topics: Aspirin; Atherosclerosis; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

Topics: Hemorrhage; Humans; Risk Assessment; Ticagrelor

The benefits of de-escalation of P2Y. We investigated the efficacy and safety of de-escalation from ticagrelor to clopidogrel after PCI by HBR status.. This is a non-prespecified post hoc analysis of the TicAgrelor Versus CLOpidogrel in Stabilized Patients with Acute Myocardial Infarction (TALOS-AMI) trial. Net adverse clinical events (a composite of cardiovascular death, myocardial infarction, stroke, or Bleeding Academic Research Consortium [BARC] bleeding type 2, 3, or 5) at 1 year post-PCI were compared between the de-escalation (clopidogrel plus aspirin) and the active control (ticagrelor plus aspirin) groups by HBR status, as defined by the modification of the Academic Research Consortium (ARC) criteria.. A total of 2,625 patients in the TALOS-AMI trial were analysed. Of these, 589 (22.4%) met the modified ARC-HBR criteria. The de-escalation group had lower primary endpoint rates than the control group in both HBR (hazard ratio [HR] 0.47, 95% confidence interval [CI]: 0.26-0.84) and non-HBR (HR 0.59, 95% CI: 0.41-0.84) patients. There were no differences in treatment effect for the primary endpoint regardless of HBR status (p for interaction=0.904). BARC bleeding type 3 or 5 was less common in the de-escalation than the control group among HBR patients only (HR 0.24, 95% CI: 0.07-0.84).. In stabilised acute myocardial infarction patients, unguided de-escalation from ticagrelor to clopidogrel was associated with a lower rate of net adverse clinical outcomes irrespective of HBR status. The effect of de-escalation of P2Y

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

It is unknown whether there are age- and gender-related differences in the safety and efficacy of potent P2Y12 inhibitors in East Asian populations with a different bleeding or ischemic propensity. Using data from the TICAKOREA (Ticagrelor Versus Clopidogrel in Asian/Korean Patients with ACS Intended for Invasive Management) trial comparing ticagrelor versus clopidogrel for 800 Korean patients with acute coronary syndrome, the safety and efficacy outcomes were compared according to age (<75 vs ≥75 years) and gender (men vs women). The primary bleeding end point was clinically significant bleeding, and the primary ischemic end point was a major adverse cardiovascular event (MACE) at 12 months. The incidences of clinically significant bleeding were significantly higher after ticagrelor than after clopidogrel in patients aged <75 years (adjusted hazard ratio [HR] 2.56, 95% confidence interval [CI] 1.40 to 4.67) but not in patients aged ≥75 years (adjusted HR 1.1, 95% CI 0.40 to 3.38). The incidences of MACEs were significantly higher after ticagrelor than after clopidogrel in patients aged ≥75 years (adjusted HR 6.14, 95% CI 1.40 to 26.90) but not in patients aged <75 years (adjusted HR 0.93, 95% CI 0.50 to 1.73). The incidences of clinically significant bleeding were significantly higher after ticagrelor than after clopidogrel in men (adjusted HR 2.69, 95% CI 1.38 to 5.24) but not in women (adjusted HR 1.49, 95% CI 0.64 to 3.46). The adjusted risks of MACEs after ticagrelor or clopidogrel were not significantly different between men and women. In conclusion, there were substantial age- and gender-related differences in bleeding and ischemic outcomes after ticagrelor or clopidogrel in Korean patients with acute coronary syndrome. Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique identifier: NCT02094963.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; East Asian People; Female; Hemorrhage; Humans; Ischemia; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

The POPular Risk Score (PRiS), a pharmacogenetic-driven algorithm consisting of CYP2C19 genotype, platelet reactivity, and clinical risk factors, is developed to evaluate ischemic risk and guide dual antiplatelet therapy (DAPT). This study aimed to evaluate the efficacy and safety of DAPT in accordance with the PRiS in patients undergoing drug-eluting stent (DES) implantation.. A total of 1757 patients recruited in this cohort study were divided into four groups according to the PRiS and type of P2Y12 receptor inhibitor treatment at discharge. The primary endpoint was major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction, stroke, definite or probable stent thrombosis, and target vessel revascularization) during 1-year follow-up. The safety endpoints were defined by Bleeding Academic Research Consortium (BARC) criteria as major bleeding (BARC 3a, 3b, 3c, and 5) and clinically relevant bleeding (BARC 2, 3a, 3b, 3c, and 5).. Among 1046 patients with PRiS < 2 and 711 patients with PRiS ≥ 2, 34.2% and 38.3% of them were treated with ticagrelor, respectively. The PRiS ≥ 2 was an independent predictor for the 1-year incidence of MACE (HR(95%CI): 2.09 (1.37-3.20), p = 0.001). Multivariable Cox regression indicated that in the PRiS ≥ 2 group, ticagrelor was superior to clopidogrel in reducing the risk of MACE (HR(95%CI): 0.53 (0.29-0.98), p = 0.042), without increasing the bleeding risk. On the other hand, in the PRiS < 2 group, clopidogrel treatment was related to a remarkably lower rate of BARC class ≥ 2 bleeding (HR(95%CI): 0.39 (0.20-0.72), p = 0.003), but comparable incidences of MACE and BARC class ≥ 3 bleeding during 1-year follow-up. Similar associations between P2Y12 receptor inhibitors and 1-year endpoints in the PRiS < 2 and PRiS ≥ 2 group could also be identified in propensity score-weighted analysis and propensity score-matched analysis.. Tailored DAPT based on the PRiS could assist in improving the prognosis of patients undergoing DES implantation. Further randomized controlled trials are required to provide more evidence for PRiS-guided DAPT.

Topics: Aged; Algorithms; Asian People; Aspirin; Cardiovascular Diseases; China; Clopidogrel; Comorbidity; Cytochrome P-450 CYP2C19; Drug-Eluting Stents; Dual Anti-Platelet Therapy; Female; Health Behavior; Hemorrhage; Humans; Male; Middle Aged; Pharmacogenetics; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk Assessment; Risk Factors; Sociodemographic Factors; Ticagrelor; Ticlopidine

We assessed the impact on periprocedural myocardial injury of a ticagrelor loading dose given <6 or >6 hours before percutaneous coronary intervention (PCI) in non-ST-elevation myocardial infarction (NSTEMI) patients at high risk. All consecutive patients pretreated with ticagrelor and undergoing PCI for a high-risk NSTEMI have been included in the present analysis. Propensity-score matching was performed to compare the outcomes between patients pretreated with ticagrelor for >6 hours or ≤6 hours. The primary outcome was the rate of periprocedural myocardial injury after PCI. We also recorded clinical outcomes, including major adverse cardiovascular events and major bleedings at 1 month. A total of 1216 patients with NSTEMI were deemed eligible for the study: 481 received a ticagrelor loading dose ≤6 hours (mean time, 4.3 ± 1.2 h) and 735 >6 hours (16.1 ± 8.4 hours) before PCI. Patients pretreated with ticagrelor for >6 hours presented more risk factors and comorbidities compared to others. In patients pretreated with ticagrelor for >6 hours, the rate of periprocedural myocardial injury was significantly lower compared to the other group, in the overall population (19.6% vs 37.8%; P < .0001) and in the matched cohort of 644 patients (18.9% vs 33.5%; P < .0001). The rate of major adverse cardiovascular events and major bleeding events did not differ between the two groups, in both unmatched and matched populations. The present study suggests that ticagrelor pretreatment reduces periprocedural myocardial injury in high-risk patients with NSTEMI undergoing PCI with expected time intervals >6 hours.

Topics: Hemorrhage; Humans; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

To establish the safety and efficacy of different dual antiplatelet therapy (DAPT) combinations in patients with acute coronary syndrome (ACS) according to their baseline ischaemic and bleeding risk estimated with a machine learning derived model [machine learning-based prediction of adverse events following an acute coronary syndrome (PRAISE) score].. Incidences of death, re-acute myocardial infarction (re-AMI), and Bleeding Academic Research Consortium 3-5 bleeding with aspirin plus different P2Y12 inhibitors (clopidogrel or potent P2Y12 inhibitors: ticagrelor or prasugrel) were appraised among patients of the PRAISE data set grouped in four subcohorts: low-to-moderate ischaemic and bleeding risk; low-to-moderate ischaemic risk and high bleeding risk; high ischaemic risk and low-to-moderate bleeding risk; and high ischaemic and bleeding risk. Hazard ratios (HRs) for the outcome measures were derived with inverse probability of treatment weighting adjustment. Among patients with low-to-moderate bleeding risk, clopidogrel was associated with higher rates of re-AMI in those at low-to-moderate ischaemic risk [HR 1.69, 95% confidence interval (CI) 1.16-2.51; P = 0.006] and increased risk of death (HR 3.2, 1.45-4.21; P = 0.003) and re-AMI (HR 2.23, 1.45-3.41; P < 0.001) in those at high ischaemic risk compared with prasugrel or ticagrelor, without a difference in the risk of major bleeding. Among patients with high bleeding risk, clopidogrel showed comparable risk of death, re-AMI, and major bleeding vs. potent P2Y12 inhibitors, regardless of the baseline ischaemic risk.. Among ACS patients with non-high risk of bleeding, the use of potent P2Y12 inhibitors is associated with a lower risk of death and recurrent ischaemic events, without bleeding excess. Patients deemed at high bleeding risk may instead be safely addressed to a less intensive DAPT strategy with clopidogrel.

Topics: Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Risk Factors; Ticagrelor; Treatment Outcome

To evaluate the effectiveness and safety of ticagrelor versus clopidogrel in patients with acute coronary syndromes (ACS) undergoing complex percutaneous coronary intervention (PCI).. It remains inconclusive whether ticagrelor is superior to clopidogrel in ACS patients undergoing complex PCI in real-world practice.. Based on an all-comers PCI registry, we compared the long-term effectiveness and safety between ticagrelor and clopidogrel in ACS patients undergoing complex PCI, defined as PCI procedures for complex lesions including bifurcation, chronic total occlusion, ostial, tortuous, calcific, diffused, thrombus-containing, and restenotic lesions. The primary ischemic outcome was a composite of cardiac death, myocardial infarction, or stroke. The safety outcome comprised Bleeding Academic Research Consortium (BARC) types 2, 3, and 5 bleeding. Propensity score matching (PSM) was performed to reduce bias.. Among ACS patients who underwent complex PCI, 4373 (35.2%) and 8065 (64.8%) received dual antiplatelet therapy based on ticagrelor and clopidogrel, respectively. The incidences of composite ischemic events (before PSM: 1.74% vs. 2.84%; after PSM: 1.50% vs. 2.65%; p < 0.01 for both) and all-cause death (before PSM: 1.23% vs. 2.12%, p < 0.01; after PSM: 1.09% vs. 1.81%, p = 0.02) were significantly lower in the ticagrelor-treated than in the clopidogrel-treated group. There was no significant difference in BARC types 2, 3, and 5 bleeding between groups.. Whilst the risk of major bleeding was comparable between the two drugs, ticagrelor was associated with a significantly lower risk of ischemic events than clopidogrel in ACS patients undergoing complex PCI.

Topics: Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Topics: Acute Coronary Syndrome; Clopidogrel; Diabetes Mellitus, Type 2; Hemorrhage; Hospitals; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

The safety and efficacy of potent P2Y12 inhibitors (Ticagrelor and Prasugrel) in dual antiplatelet therapy (DAPT) with aspirin in elderly acute coronary syndrome (ACS) patients remains unclear.. All ACS patients aged 75 years and older treated with Percutaneous Coronary Intervention (PCI) from PRAISE dataset were included. The safety and efficacy of Ticagrelor vs Clopidogrel was evaluated with inverse probability of treatment weighting (IPTW). Sensitivity analysis was performed for patients older or equal than 85 years old. All-cause mortality was the primary endpoint, while myocardial infarction (MI), Bleeding Academic Research Consortium (BARC) 3-5 bleedings and Major and Net Adverse Clinical and Cardiac Events (MACE and NACE) were the secondary ones.. 4287 patients were included, 3197 treated with Clopidogrel and 1090 with Ticagrelor. After 16 ± 3 months, Ticagrelor showed neutral effect on NACE and mortality (HR 0.98; 0.63-1.52, p = 0.94 and HR 0.38; 0.14-1.04, p = 0,06), reduced risk of MACE and MI (HR 0.82; 0.23-0.91, p = 0.03 and HR 0.43; 0.14-0.89, p = 0.04) and increased risk of BARC 3-5 bleeding (HR 2.14; 1.19-3.85, p = 0.001). In very elderly patients (≥85 years) Ticagrelor decreased risk of MI and increased risk of bleeding (HR 0.69; 0.22-0.95, p = 0.04 and HR 2.36; 1.02-5.52, p = 0.04, all 95%CI) with neutral effect on NACE and MACE.. In elderly ACS patients treated with PCI, Ticagrelor was associated with neutral effect on all-cause mortality, lower risk MACE and MI compared with Clopidogrel. Such benefit was counterbalanced by increased risk of major bleedings. These results were consistent among patients aged 85 years and older.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Clopidogrel; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Registries; Ticagrelor; Treatment Outcome

Stroke after acute coronary syndrome (ACS) can be devastating. It is uncertain whether the risks of ischaemic stroke or intracranial haemorrhage (ICH) are associated with different choices of P2Y12 inhibitors (potent P2Y12 inhibitors such as ticagrelor and prasugrel vs clopidogrel). Even though East Asians are known to have different thrombotic and haemorrhagic profiles from Caucasians, data on Chinese patients are sparse.. This was a retrospective cohort study conducting in Chinese patients with ACS who underwent first-ever percutaneous coronary intervention from 14 hospitals in Hong Kong between 2010 and 2017. The primary efficacy endpoint was ischaemic stroke. The secondary efficacy endpoint was a composite outcome of thrombotic events including all-cause mortality, non-fatal myocardial infarction and ischaemic stroke. The primary safety endpoint was ICH. The secondary safety endpoint was a composite of major bleeding events.. After adjustment of baseline characteristics by 1:1 propensity score matching, a total of 6220 patients (3110 on each group) were analysed. Compared with clopidogrel, potent P2Y12 inhibitors were associated with a lower risk of ischaemic stroke (HR 0.57; 95% CI 0.37 to 0.87; p=0.008) and a lower risk of thrombotic events (HR 0.77; 95% CI 0.66 to 0.90; p=0.001). Potent P2Y12 inhibitor was associated with similar risk of ICH (HR 0.65; 95% CI 0.34 to 1.25, p=0.20) and major bleeding (HR 0.83; 95% CI 0.68 to 1.01, p=0.069).. Potent P2Y12 inhibitors were associated with a lower adjusted risk of ischaemic stroke and thrombotic events, compared with clopidogrel. The risks of ICH and major bleeding were similar.

Topics: Acute Coronary Syndrome; Brain Ischemia; China; Clopidogrel; Hemorrhage; Hemorrhagic Stroke; Humans; Intracranial Hemorrhages; Ischemic Stroke; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Stroke; Ticagrelor

Activated coagulation factor XI (FXIa) contributes to the development and propagation of thrombosis but plays only a minor role in hemostasis; therefore, it is an attractive antithrombotic target.. To evaluate the pharmacology of asundexian (BAY 2433334), a small molecule inhibitor targeting FXIa, in vitro and in various rabbit models.. The effects of asundexian on FXIa activity, selectivity versus other proteases, plasma thrombin generation, and clotting assays were evaluated. Antithrombotic effects were determined in FeCl. Asundexian inhibited human FXIa with high potency and selectivity. It reduced FXIa activity, thrombin generation triggered by contact activation or low concentrations of tissue factor, and prolonged activated partial thromboplastin time in human, rabbit, and various other species, but not in rodents. In the FeCl. Asundexian is a potent oral FXIa inhibitor with antithrombotic efficacy in arterial and venous thrombosis models in prevention and intervention settings, without increasing bleeding.

Topics: Animals; Anticoagulants; Aspirin; Factor XIa; Fibrinolytic Agents; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Rabbits; Thrombin; Thrombosis; Ticagrelor

The THEMIS trial demonstrated that in high-risk patients with stable coronary artery disease and diabetes without previous myocardial infarction or stroke, ticagrelor, in addition to aspirin, reduced the incidence of ischemic events but increased major bleeding. Identification of patients who could derive the greatest net benefit from the addition of ticagrelor appears important. We used the CRUSADE bleeding risk score to risk stratify the THEMIS population.. The population was divided into tertiles: score ≤22, 23 to 33, and ≥34. In each tertile, primary efficacy (composite of cardiovascular death, myocardial infarction, or stroke) and safety (TIMI major bleeding) outcomes were analyzed. NACE (net adverse clinical events) was defined as the irreversible harm composite, in which all-cause death, myocardial infarction, stroke, amputations, fatal bleeds, and intracranial hemorrhage were counted.. In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, only those at the lower end of the bleeding risk spectrum according to the CRUSADE score derived net benefit from ticagrelor.

Topics: Coronary Artery Disease; Diabetes Mellitus; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Assessment; Stroke; Ticagrelor; Treatment Outcome

Despite implementation of new interventional techniques and therapeutic advances, elderly patients with acute coronary syndrome (ACS) continue to be susceptible to in-hospital bleeding compared with younger ones. Thus, we investigated the incidence of in-hospital bleeding events and associated risk factors in elderly (≥ 75°years) ACS patients. We also wanted to define the bleeding sites, characteristics, and associated mortality. Bleeding Academic Research Consortium (BARC) classification type 2, 3, or 5 was used to define bleeding events. Overall, 539 patients were included in the study (mean age: 82.5 ± 4.8°years; 282 (52.3%) females). Of these patients, 69 (12.8%) developed in-hospital bleeding. Factors that were independently related with in-hospital bleeding were age (odds ratio (OR): 1.08; 95% confidence interval (CI): 1.011.14,

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Female; Hemorrhage; Hospitals; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Tirofiban; Treatment Outcome

To evaluate the impact of perioperative P2Y12 receptor inhibitor therapy among patients undergoing cardiac surgery within 1 year of percutaneous coronary intervention (PCI).. Patients undergoing cardiac surgery in the year post-PCI at three tertiary care centres between 2011 and 2018 were stratified into those who had received at least one dose of P2Y12 inhibitor prior to surgery (within 5 days for clopidogrel or prasugrel, or within 3 days for ticagrelor) and those who had not. The outcomes of interest were major adverse cardiac and cerebrovascular events (MACCEs) and bleeding. Among 20 279 PCI patients, 359 (1.8%) underwent cardiac surgery in the ensuing year, 76.3% of whom received coronary artery bypass grafts. Overall, 33 (9.2%) MACCEs and 85 (23.7%) bleeding events occurred within 30 days post-cardiac surgery. Perioperative P2Y12 inhibition (N = 133, 37%) was not associated with the risk of MACCEs or bleeding, despite numerically lower rates of myocardial infarction or stent thrombosis (0.0% vs. 2.6%; P = 0.089). Patients who continued the P2Y12 inhibitor until the day of surgery (N = 60, 17%) had significantly higher bleeding risk [adjusted odds ratio 2.93, 95% confidence interval 1.53-5.59)]. Predictors of MACCEs included a time interval from PCI to cardiac surgery of ≤30 days and reduced ejection fraction, whereas urgent/emergent surgery predicted bleeding. Chronic kidney disease and myocardial infarction as indication for PCI predicted both MACCEs and bleeding.. Among patients undergoing cardiac surgery in the year after PCI, the perioperative risk of ischaemic and bleeding events might be influenced by P2Y12 inhibitor therapy in addition to other risk parameters, including the timing and urgency of the procedure.

Topics: Cardiac Surgical Procedures; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Purinergic P2Y Receptor Antagonists; Ticagrelor

Age is a strong predictor of adverse outcomes due both to a higher risk of bleeding and ischemia. The purpose of this study was to evaluate the safety and efficacy of ticagrelor in elderly patients.. Patients ≥75 years of age admitted to our center from January, 2015 to December, 2019 who had undergone percutaneous coronary intervention (PCI) and received dual antiplatelet therapy (DAPT) were included in our study. Eligible patients were divided into clopidogrel and ticagrelor groups according to the P2Y. Of 1505 patients enrolled in this study, 442 were assigned to ticagrelor group and 1063 were assigned to clopidogrel group. The incidence of BARC 2, 3, and 5 bleeding (HR, 2.304; 95% CI, 1.540-3.447), and any bleeding (HR, 2.476; 95% CI, 1.802-3.403) in ticagrelor group was significantly higher than clopidogrel group. There were no significant difference between the two groups with respect to BARC 3 and 5 bleeding (HR, 1.566; 95% CI, 0.767-3.198) and MACCEs (HR, 0.957; 95% CI, 0.702-1.305).. Compared with clopidogrel, DAPT with ticagrelor significantly increased the risk of BARC 2, 3, and 5 bleeding without reducing MACCEs in elderly patients who underwent PCI.. The study was retrospectively registered in

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Cohort Studies; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

The goal of this work was to investigate the short-term time-course benefit and risk of ticagrelor with aspirin in acute mild-moderate ischemic stroke or high-risk TIA in The Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and ASA for Prevention of Stroke and Death (THALES) trial.. In an exploratory analysis of the THALES trial, we evaluated the cumulative incidence of irreversible efficacy and safety outcomes at different time points during the 30-day treatment period. The efficacy outcome was major ischemic events defined as a composite of ischemic stroke or nonhemorrhagic death. The safety outcome was major hemorrhage defined as a composite of intracranial hemorrhage and fatal bleedings. Net clinical impact was defined as the combination of these 2 endpoints.. This analysis included a total of 11,016 patients (5,523 in the ticagrelor-aspirin group, 5,493 in the aspirin group) with a mean age of 65 years, and 39% were women. The reduction of major ischemic events by ticagrelor occurred in the first week (4.1% vs 5.3%; absolute risk reduction 1.15%, 95% CI 0.36%-1.94%) and remained throughout the 30-day treatment period. An increase in major hemorrhage was seen during the first week and remained relatively constant in the following weeks (absolute risk increase ≈0.3%). Cumulative analysis showed that the net clinical impact favored ticagrelor-aspirin in the first week (absolute risk reduction 0.97%, 95% CI, 0.17%-1.77%) and remained constant throughout the 30 days.. In patients with mild-moderate ischemic stroke or high-risk TIA, the treatment effect of ticagrelor-aspirin was present from the first week. The ischemic benefit of ticagrelor-aspirin outweighs the risk of major hemorrhage throughout the treatment period, which may support the use of 30-day treatment with ticagrelor and aspirin in these patients.. This study provides Class II evidence that, for patients with mild-moderate ischemic stroke or high-risk TIA, the ischemic benefit of ticagrelor-aspirin outweighs the risk of major hemorrhage throughout the 30-day treatment period.

Topics: Aged; Aspirin; Drug Therapy, Combination; Female; Hemorrhage; Humans; Ischemia; Ischemic Attack, Transient; Ischemic Stroke; Male; Platelet Aggregation Inhibitors; Stroke; Ticagrelor

Tirofiban has been used historically as a bridge to platelet inhibition with clopidogrel in ST-segment myocardial infarction (STEMI) during percutaneous coronary intervention (PCI) to prevent stent thrombosis. However, ticagrelor and prasugrel reach similar levels of platelet inhibition at 30 minutes to that of clopidogrel at 6 hours, challenging the need for long-duration tirofiban. This 1-year, retrospective cohort study compared ischemic and bleeding outcomes of short-duration versus long-duration tirofiban regimens in patients with STEMI who received ticagrelor or prasugrel at the time of PCI. The primary outcome was major adverse cardiovascular events (MACEs) including cardiovascular mortality, recurrent myocardial infarction, urgent target vessel revascularization, or stroke. Secondary outcomes included individual MACE, all-cause mortality, bleeding events defined by the International Society on Thrombosis and Hemostasis, thirty-day readmissions for MACE and bleeding, and tirofiban pharmacy cost. A total of 283 charts were reviewed and 177 included (short duration n = 57; long duration n = 120). MACE rates were similar between short-duration and long-duration groups (0 [0%] vs. 5 [4.2%]; P = 0.18), including 4 cardiovascular deaths and 1 recurrent myocardial infarction. Bleeding event rates were also similar in short-duration versus long-duration groups including major bleeds (2 [3.5%] vs. 2 [1.7%]; P = 0.60) and clinically relevant nonmajor bleeds (3 [5.3%] vs. 9 [7.5%]; P = 0.75). Cost analysis indicated lower pharmacy cost with the short-duration group. In this cohort of patients with STEMI receiving a fast-acting P2Y12 inhibitor, the length of tirofiban infusion did not affect ischemic or bleeding outcomes, yet short-duration regimens were lower cost.

Topics: Clopidogrel; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Retrospective Studies; ST Elevation Myocardial Infarction; Thrombosis; Ticagrelor; Tirofiban; Treatment Outcome

Clopidogrel in combination with aspirin after acute coronary syndromes (ACS) reduces recurrent ischaemic events compared to aspirin alone. Further reductions in events have been demonstrated when clopidogrel is replaced by ticagrelor or prasugrel albeit with increases in bleeding. There are few studies documenting the patterns of use of P2Y12 inhibitors or their association with outcomes in the Australian population.. To describe the patterns of use of each P2Y12 inhibitor and to determine the associations between initial P2Y12 inhibitor use and outcomes.. Data were extracted from Cooperative National Registry of ACS, Guideline Adherence and Clinical Events (CONCORDANCE)-a prospective database of patients presenting to 43 sites across Australia with ACS. Patients were stratified based on first antiplatelet agent received. Baseline clinical characteristics were compared between these patient groups and hospital investigations, management as well as in-hospital and 12 months outcomes (death, a composite of cardiac-related death, myocardial infarction, and stroke, and major bleeding) were compared between the three treatment cohorts after adjustment for differences in baseline characteristics.. Mean ages of the clopidogrel (n=7,537), ticagrelor (n=1,878), and prasugrel (n=347) cohorts were 65, 63, and 58 yrs respectively (p<0.0001), the mean Global Registry of Acute Coronary Events (GRACE) risk scores were 107, 104, and 102 (p=0.0016). The ticagrelor and prasugrel cohorts were more likely to receive percutaneous coronary intervention (PCI) (clopidogrel 52%, ticagrelor 66%, prasugrel 88%, p<0.0001), and evidence based medications (≥4 guideline indicated medications: clopidogrel 76%, ticagrelor 82%, prasugrel 93%, p<0.0001). Patients treated with ticagrelor and prasugrel were less likely to experience in-hospital death (clopidogrel 2.5%, ticagrelor 1.4%, prasugrel 1.2%, p=0.05), major adverse cardiac events (MACE) (clopidogrel 5.1%, ticagrelor 3.0%, prasugrel 3.5% [p=0.01]), or bleeding (clopidogrel 8.4%, ticagrelor 4.6%, prasugrel 7.5% [p<0.001]) compared to clopidogrel. These differences were no longer apparent after multivariable adjustment. There was no difference in outcomes between cohorts at 12 months.. In Australia, ticagrelor and prasugrel are used in younger patients who are more likely to undergo percutaneous coronary intervention (PCI) and receive evidence based therapy. Patients receiving clopidogrel were more likely to experience in hospital ischaemic or bleeding events but this was explained by their higher baseline risk. Selection of therapy was not associated with any difference in outcomes at 12-month follow-up, but our findings suggest there is room for improvement towards guideline-driven usage of P2Y12 inhibitors.

Topics: Acute Coronary Syndrome; Aspirin; Australia; Clopidogrel; Hemorrhage; Hospital Mortality; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

The risk of ticagrelor-related bleeding events remains a major clinical concern, especially in East Asian populations. Previous studies have reported higher ticagrelor exposure in Asian patients than in Caucasians. This prompted us to investigate the correlation between ticagrelor concentrations and bleeding events.. Patients diagnosed with acute coronary syndrome and receiving dual antiplatelet therapy (aspirin and ticagrelor) were enrolled and followed up for 12 months. Trough plasma concentrations of ticagrelor and a major active metabolite were assayed, and 10 single nucleotide polymorphisms associated with ticagrelor pharmacokinetics and safety were also identified.. A total of 631 patients were included and 133 patients had bleeding academic research consortium type 1 or 2 bleeding event. The median ticagrelor concentration (interquartile range) was significantly higher in patients with bleeding events than that in patients without bleeding events (322.6 ng/mL [196.2-458.0 ng/mL] vs. 222.1 ng/mL [140.4-341.9 ng/mL], P < .001). According to the receiver operating characteristic curve, the cut-off value for ticagrelor levels predicting bleeding events was 363.3 ng/mL (area under the curve = 0.65; P < .001, 95% Cl: 0.595-0.700). Pharmacogenomics results showed that P2Y12 (rs6787801, P = .024) and P2Y12 (rs6785930, P = .048) were statistically associated with ticagrelor levels and bleeding events, respectively.. Ticagrelor plasma concentrations were associated with bleeding events in Chinese patients with acute coronary syndrome.

Topics: Acute Coronary Syndrome; Aspirin; China; Clopidogrel; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

Low platelet reactivity levels are associated with higher risk of bleeding in patients receiving dual antiplatelet therapy relative to patients with optimal platelet blockade. This study set out to evaluate the prevalence of low platelet reactivity in patients with acute myocardial infarction treated with ticagrelor and aspirin.. Patients admitted with acute myocardial infarction who were already undergoing dual antiplatelet therapy with aspirin and ticagrelor were enrolled. Blood samples were collected 1 hour before and 2 hours after the maintenance dose of ticagrelor to investigate trough and the peak effects of the drug respectively. Platelet reactivity was measured by three methods: Multiplate®, PFA-100® with Innovance® PFA-P2Y cartridge and PFA-100® with Collagen/ADP cartridge. Platelet reactivity was assessed in the presence of peak levels of ticagrelor and defined according to previously validated cut-offs for each method (<19 AUC, >299 seconds and >116 seconds respectively). The level of significance was set at p<0.05.. Fifty patients were enrolled (44% with ST-elevation). Median duration of DAPT was 3 days (interquartile range, 2-5 days). On average, peak and trough platelet reactivity were markedly low and did not differ between different methods. Low platelet reactivity was common, but varied according to analytic method (PFA-100®/Innovance®PFA-P2Y: 86%; Multiplate®: 74%; PFA-100®/Collagen/ADP: 48%; p<0.001).. Low platelet reactivity was very common in patients with acute myocardial infarction submitted to dual antiplatelet therapy with ticagrelor and aspirin. Findings of this study justify the investigation of less intensive platelet inhibition strategies aimed at reducing the risk of bleeding in this population, such as lower dose regimens or monotherapy with P2Y12 inhibitors.

Topics: Adenosine Diphosphate; Aspirin; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

In this study, we aimed to determine whether potent agents affect in-hospital bleeding and mortality compared to clopidogrel in patients with the acute coronary syndrome in whom tirofiban and P2Y12 inhibitor are used together.. Patients who were treated interventionally between 2015 and 2020 and were using tirofiban were retrospectively screened. Clinical, laboratory, and angiographic findings were obtained from the hospital database. Patients were analyzed by dividing them into clopidogrel and prasugrel/ticagrelor groups.. Acute coronary syndrome patients (n = 227) who were treated interventionally were included in this retrospective study. Clopidogrel was given to 93 (41%), ticagrelor to 112 (49.3%), and prasugrel to 22 of the patients (9.7%). Compared to the ticagrelor/prasugrel group, the clopidogrel group was older and more were women, and the history of hypertension and previous coronary artery disease was higher (P, respectively: <.001; .001; .008; .0045). The creatinine value was higher, the basal hemoglobin was lower, and the GRACE (Global Registry of Acute Coronary Events) and CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) scores were higher (P, respectively: .026; .002; .002; <.001). The in-hospital bleeding rate was signifi- cantly higher in the clopidogrel group (P < .001). Although the in-hospital mortality rate was higher, it was not statistically significant (P = .07). Regression analysis showed that GRACE score and gender were associated with in-hospital mortality (P < .001; P=.031, respectively), and only age was associated with in-hospital bleeding (P < .001). No relationship was found with P2Y12 inhibitor.. In our study, we found that the combined use of potent P2Y12 inhibitor with tiro- fiban in acute coronary syndrome patients treated interventionally was not different from the use of clopidogrel in terms of in-hospital bleeding and mortality.

Topics: Acute Coronary Syndrome; Clopidogrel; Female; Hemorrhage; Hospitals; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Ticagrelor; Tirofiban; Treatment Outcome

To compare the effectiveness and safety of clopidogrel, ticagrelor, and prasugrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI).. Nationwide, registry-based study of STEMI patients treated with primary PCI (2011-17) and subsequently with aspirin and a P2Y12 inhibitor. The effectiveness outcome was major adverse cardiovascular events (MACE) defined as a composite of recurrent myocardial infarction, repeat revascularization, stroke, or cardiovascular death at 12 months. The safety outcome was bleeding requiring hospitalization at 12 months. Multivariable logistic regression with average treatment effect modeling was used to calculate absolute and relative risks for outcomes standardized to the distributions of demographic characteristics of all included subjects. We included 10 832 patients; 1 697 were treated with clopidogrel, 7 508 with ticagrelor, and 1,627 with prasugrel. Median ages were 66, 63, and 59 years (P < 0.001). Standardized relative risks of MACE were 0.75 for ticagrelor vs. clopidogrel (95% confidence interval [CI], 0.64-0.83), 0.84 for prasugrel vs. clopidogrel (95% CI, 0.73-0.94), and 1.12 for prasugrel vs. ticagrelor (95% CI, 1.00-1.24). Standardized relative risks of bleeding were 0.77 for ticagrelor vs. clopidogrel (95% CI, 0.59-0.93), 0.89 for prasugrel vs. clopidogrel (95% CI, 0.64-1.15), and 1.17 for prasugrel vs. ticagrelor (95% CI, 0.89-1.45).. Ticagrelor and prasugrel were associated with lower risks of MACE after STEMI than clopidogrel, and ticagrelor was associated with a marginal reduction compared with prasugrel. The risk of bleeding was lower with ticagrelor compared with clopidogrel, but did not significantly differ between ticagrelor and prasugrel.

Topics: Aspirin; Clopidogrel; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Registries; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Current guidelines recommend the use of potent antiplatelet agents in patients undergoing percutaneous coronary intervention (PCI) following an acute coronary syndrome (ACS). However, data about optimal platelet inhibition in severe renal insufficiency patients are scarce. The purpose of this study is to determine if ticagrelor is more effective than clopidogrel in patients with ACS and severe renal insufficiency treated with PCI.. We retrospectively enrolled patients with ACS and severe renal insufficiency (eGFR ≤ 30 ml/min·1.73 m. A total of 276 patients with ACS and severe renal insufficiency who were treated with PCI with ticagrelor (. Ticagrelor did not improve the major adverse cardiovascular events and all-cause mortality when compared to clopidogrel, but significantly increased the risk of bleeding in Chinese patients with ACS and severe renal insufficiency undergoing PCI.

Topics: Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Humans; Percutaneous Coronary Intervention; Renal Insufficiency; Retrospective Studies; Ticagrelor; Treatment Outcome

Taking ischemic and bleeding risks into consideration, insufficient data exist on dual antiplatelet therapy after percutaneous coronary intervention in elderly Chinese patients with coronary artery disease.. We aimed to investigate the effectiveness and safety of ticagrelor in comparison with clopidogrel on a background of aspirin for elderly Chinese patients with coronary artery disease 12 months after percutaneous coronary intervention.. A single-center retrospective cohort study was conducted. Selected from patients with coronary artery disease aged ≥ 75 years from January 2010 to July 2019, 908 eligible subjects receiving dual antiplatelet therapy after percutaneous coronary intervention for up to 12 months were consecutively enrolled in the study. The included patients received ticagrelor in combination with aspirin (n = 264) or clopidogrel in combination with aspirin (n = 644). Effectiveness endpoints were evaluated by the major adverse cardiovascular events, encompassing all-cause death, non-fatal myocardial infarction, and clinically driven revascularization. The safety endpoints were recorded as the incidence of Bleeding Academic Research Consortium bleeding.. The patients who were treated with ticagrelor were slightly younger than those who were treated with clopidogrel (79.1 ± 3.7 vs 80.7 ± 4.5 years, p < 0.01). The ticagrelor cohort contained a higher percentage of patients undergoing a prior percutaneous coronary intervention (37.9% vs 24.5%, p < 0.01), and a lower percentage of smokers (19.3% vs 27.2%, p < 0.05), compared with the clopidogrel cohort. The levels of glucose, total cholesterol, and low-density lipoprotein-cholesterol in the ticagrelor group were higher while the level of triglycerides and high-density lipoprotein-cholesterol were lower (p < 0.05) than those in the clopidogrel group. Left main percutaneous coronary intervention was performed more frequently among the ticagrelor-treated patients (23.5% vs 9.3%, p < 0.01), while patients in the clopidogrel group underwent more left circumflex percutaneous coronary intervention (34.3% vs 23.1%, p < 0.01). We found that ticagrelor was associated with a lower incidence of major adverse cardiovascular events than clopidogrel using the inverse probability of treatment weighting model (odds ratio, 0.493; 95% confidence interval 0.356-0.684). There was no difference in terms of the risk of Bleeding Academic Research Consortium bleeding between the two groups (p > 0.05).. Ticagrelor was associated with a lower incidence of major adverse cardiovascular events than clopidogrel at 12 months in elderly Chinese patients with coronary artery disease, without a significant increase of Bleeding Academic Research Consortium bleeding events.

Topics: Acute Coronary Syndrome; Aged; Aspirin; China; Cholesterol; Clopidogrel; Cohort Studies; Coronary Artery Disease; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Retrospective Studies; Ticagrelor; Treatment Outcome

The benefits of potent antithrombotic therapy usually come at the expense of a higher risk of bleeding. The efficacy and safety of ticagrelor in elderly East Asian populations remains debated due to the concerns about the imbalance of ischemic and bleeding risks. This study aimed to compare the impact of clopidogrel with ticagrelor on clinical outcomes in East Asian patients aged ≥75 years with acute coronary syndrome (ACS) using data from an institutional registry. We assessed the treatment effect of ticagrelor versus clopidogrel based on propensity scores and multivariate Cox proportional hazards models. A total of 2775 ACS patients were included, of which 235 (8.5%) were treated with ticagrelor. The primary efficacy outcome occurred in 11.9% of patients treated with ticagrelor versus 8.8% treated with clopidogrel. There was no significant association between treatment with ticagrelor and a lower risk of the primary efficacy outcome (p = .156). However, the incidences of all-cause death (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.02 to 2.79) and major bleeding (adjusted HR 2.20, 95% CI 1.06 to 4.56) were significantly higher in patients treated with ticagrelor than clopidogrel. In elderly patients with ACS from East Asia, the efficacy of clopidogrel was comparable to ticagrelor, while ticagrelor is associated with an increased risk of mortality and major bleeding.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Dimaprit; Fibrinolytic Agents; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Registries; Ticagrelor; Treatment Outcome

Aim    To study specific features of administering platelet P2Y12 receptor inhibitors to patients with myocardial infarction (MI) in real-life clinical practice; to reveal a possible inconsistency of the therapy with clinical guidelines; to evaluate the patients' compliance with the medication at the outpatient stage; and to outline major direction for improving quality of the antiplatelet treatment.Material and methods    REGION-MI is a multicenter prospective, observational study. The observational period is divided into 3 stages: during the stay in the hospital and at 3 and 12 months following the inclusion into the registry. Information about the drug therapy (used at the time of hospitalization, administered before the hospitalization, received in the hospital, and prescribed at discharge from the hospital) was recorded in the patient's individual registration card. Information about the antiplatelet treatment at 6 months following enrollment into the study was obtain by phone.Results    The study included 4 553 patients. Dual antiplatelet therapy was administered after MI to 94.4 % patients: clopidogrel was administered to 52 %, ticagrelor to 42.2 %, and prasugrel to 11 patients (0.2 %). Ticagrelor was administered significantly more frequently in ST segment elevation myocardial infarction (STEMI) than in NSTEMI, 45 % and 33 %, respectively (p<0.001); clopidogrel was also administered more frequently to patients with STEMI than with NSTEMI, 59 % and 50 %, respectively. According to ARC-HBR criteria, in MI and a high risk of bleeding, clopidogrel was administered more frequently than ticagrelor (p <0.001). Ticagrelor was significantly more frequently administered to patients with MI and a low risk of bleeding than to patients with a high risk (p<0.001). In STEMI and a low risk of bleeding, ticagrelor was administered somewhat more frequently than clopidogrel, 56 % and 44 %, respectively (р<0.05). In NSTEMI and a low risk of bleeding, clopidogrel was administered more frequently than ticagrelor, 53 % and 47 %, respectively (p<0.05). At 6 months post-MI, 94 % of patients continued taking one of the P2Y12 inhibitors.Conclusion    According to data of the REGION-MI registry, the frequency of administering P2Y12 inhibitors to patients with acute MI was high, and the patients' compliance with this therapy was high at 6 months following MI. Although ticagrelor (the most available drug of all powerful platelet P2Y12 receptor inhibitors) has be

Topics: Anticoagulants; Clopidogrel; Hemorrhage; Humans; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

This study aims to compare the effects of ticagrelor and clopidogrel on platelet function, cardiovascular prognosis, and bleeding in patients with unstable angina pectoris.. Patients with unstable angina pectoris undergoing percutaneous coronary intervention (PCI) were enrolled (January 2018-December 2019). In total, 212 patients were treated with ticagrelor (90 mg twice daily) and 210 patients were treated with clopidogrel (75 mg once daily). Thromboelastography and light transmission aggregometry were used to measure the platelet aggregation rate (PAR). High-sensitivity troponin T (hs-TnT), pro-brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (CRP), and heart-type fatty acid-binding protein (h-FABP) were measured to assess myocardial injury after PCI. Cardiovascular prognosis and bleeding events were evaluated in hospital and 12 months after discharge.. The PAR was significantly slower with ticagrelor (P < 0.001). hs-TnT, NT-proBNP, CRP, and h-FABP increased after compared with before PCI in both groups (P < 0.05). hs-TnT (P < 0.001) and h-FABP (P < 0.001) increased more significantly with clopidogrel. The in-hospital and 12-month major adverse cardiovascular event (MACE) rates were not significantly different between the two groups. The in-hospital total bleeding event rate was higher with ticagrelor (P < 0.05). Minor bleeding and total bleeding were more frequent at the 12-month follow-up in the ticagrelor group (P < 0.05).. Ticagrelor was more effective in suppressing the PAR than clopidogrel and reduced PCI-induced myocardial injury in patients with unstable angina pectoris. However, it increased in-hospital and 12-month bleeding events and had no benefit on in-hospital and 12-month MACEs.

Topics: Angina, Unstable; Clopidogrel; Fatty Acid Binding Protein 3; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prognosis; Ticagrelor; Treatment Outcome

East Asians have a higher risk of bleeding than Europeans when treated with ticagrelor. This study aimed to explore genetic indicators related to the high bleeding propensity in East Asian patients with acute coronary syndrome (ACS) using ticagrelor.. A multicenter prospective cohort study.. Four sub center hospitals participating the study.. Between March 2018 and July 2021, 208 patients with ACS were administered ticagrelor and underwent genetic testing.. Patients were enrolled and followed up for bleeding events for 12 months. Single-nucleotide polymorphisms (SNPs) were detected using whole-exome sequencing. SNPs significantly associated with cumulative bleeding events within 1-, 6-, and 12-month follow-ups were selected (p < 0.01). Among these, SNPs showing a difference of ≥2 fold in their distribution frequency among East Asians and Europeans were selected.. Among all patients, 96.60% received ticagrelor plus aspirin or cilostazol, and 42.3% suffered from bleeding events during 12-month follow-up. Furthermore, 22 SNPs of 15 genes were found to have a significant association with cumulative bleeding events within 1-, 6-, and 12-month follow-ups. Among these SNPs, FIG4 rs2295837 (A>T) variant had the strongest association with bleeding events within 1 month (p = 1.28 × 10. Fifteen genes, including PROK2, HRNR, and FIG4, were potential biomarkers of high bleeding propensity in East Asian patients with ACS using ticagrelor.

Topics: Acute Coronary Syndrome; Calcium-Binding Proteins; East Asian People; Flavoproteins; Gastrointestinal Hormones; Hemorrhage; Humans; Intermediate Filament Proteins; Neuropeptides; Phosphoric Monoester Hydrolases; Prospective Studies; Ticagrelor

In patients with prior myocardial infarction (MI) on aspirin, the addition of ticagrelor reduces ischaemic risk but increases bleeding risk. The simultaneous assessment of baseline ischaemic and bleeding risk may assist clinicians in selecting patients who are most likely to have a favourable risk/benefit profile with long-term ticagrelor.. PEGASUS-TIMI 54 randomized 21 162 prior MI patients, 13 956 of which to the approved 60 mg dose or placebo and who had all necessary data. The primary efficacy endpoint was cardiovascular death, MI, or stroke, and the primary safety outcome was TIMI major bleeding; differences in Kaplan-Meier event rates at 3 years are presented. Post-hoc subgroups based on predictors of bleeding and ischaemic risk were merged into a selection algorithm. Patients were divided into four groups: those with a bleeding predictor (n = 2721, 19%) and then those without a bleeding predictor and either 0-1 ischaemic risk factor (IRF; n = 3004, 22%), 2 IRF (n = 4903, 35%), or ≥3 IRF (n = 3328, 24%). In patients at high bleeding risk, ticagrelor increased bleeding [absolute risk difference (ARD) +2.3%, 95% confidence interval (CI) 0.6, 3.9] and did not reduce the primary efficacy endpoint (ARD +0.08%, 95% CI -2.4 to 2.5). In patients at low bleeding risk, the ARDs in the primary efficacy endpoint with ticagrelor were -0.5% (-2.2, 1.3), -1.5% (-3.1, 0.02), and -2.6% (-5.0, -0.24, P = 0.03) in those with ≤1, 2, and 3 risk factors, respectively (P = 0.076 for trend across groups). There were significant trends for greater absolute risk reductions for cardiovascular death (P-trend 0.018), all-cause mortality (P-trend 0.027), and net outcomes (P-trend 0.037) with ticagrelor across these risk groups.. In a post-hoc exploratory analysis of patients with prior MI, long-term ticagrelor therapy appears to be best suited for those with prior MI with multiple IRFs at low bleeding risk.. NCT01225562 ClinicalTrials.gov.

Topics: Adenosine; Hemorrhage; Humans; Ischemia; Myocardial Infarction; Patient Selection; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk Factors; Secondary Prevention; Ticagrelor; Treatment Outcome

Long term dual antiplatelet therapy (LTDAPT), with ticagrelor 60 mg and low-dose aspirin, is indicated after acute coronary syndrome (ACS) for the secondary prevention of atherothrombotic events in high-risk patients with a history of ACS of at least 1 year. LTDAPT had a good tolerability and safety profile, but the risk of TIMI major bleeding was increased. However, even non-significant bleeding may be important because it has an effect on the quality of life and therefore may lead to treatment discontinuation. We, therefore, evaluated patients' experiences with LTDAPT and the impact of nuisance bleeding on quality of life and treatment adherence. We retrospectively reviewed 225 patients in follow-up after ACS with at least one high-risk condition, treated with ticagrelor 60 mg twice daily (after 90 mg twice daily for 12 months). The outpatient follow-up program after hospitalization provides a visit on day 30 after discharge, then after 3 months, continuing with six-monthly checks. We assessed the presence and intensity of bleeding, as well as health-related quality of life (HRQoL), at each visit. The TIMI score was used to determine the severity of the bleeding. Any overt bleeding event that did not meet the major and minor criteria was labeled "minimal" and could be framed as "nuisance bleeding." The HRQoL was assessed by the EuroQol-5 and Dimension (EQ-5D) visual analog scale (VAS) score. Minimal bleedings were present in 49 patients (21%), but only in one case (by decision of the patient) there was a cause for discontinuation of therapy. However, 39 (79%) subjects had asked for opinions on stopping the therapy during the telephone consultation. Factors influencing LTDAPT knowledge included access to medication counselling, engaging with information communicated during medication counselling, and access to timely, relevant and expert information and advice after discharge from the hospital. All adverse events, judged to be "not serious" in trials, may have an effect on the quality of life and therefore may lead to treatment discontinuation. The authors underline the importance of careful outpatient follow-up and ongoing counselling, to check out compliance and possible adverse effect of LTDAPT.

Topics: Acute Coronary Syndrome; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Quality of Life; Referral and Consultation; Retrospective Studies; Telephone; Ticagrelor; Treatment Outcome

Clopidogrel is the most commonly prescribed P2Y. To determine which factors most greatly influence cardiology-provider and patient selection of P2Y. Single-center study assessed survey responses from 32 cardiology-providers who prescribed and 105 patients who received clopidogrel, prasugrel, or ticagrelor for ACS or stent placement. Respondents ranked factors influencing P2Y. Cardiology-providers ranked risk of bleeding, comfort/experience, and cost as most influential. Patients ranked risk of drug interaction, adverse effects, and reduction in myocardial infarction as most influential. Significant differences between cardiology-providers and patients were found for 5 of 8 factors. Cardiology-providers ranked once daily administration (p = 0.01), risk of bleeding (p = 0.002), and cost (p < 0.001) as more important than patients. Patients ranked risk of adverse effects (p = 0.007) and drug interactions (p = 0.005) as more important than cardiology-providers. Cardiology-providers prescribed ticagrelor 42.3% of the time following ACS, though 78.1% ranked it as their preferred agent. Patients were prescribed ticagrelor 9.3% of the time, though 55.7% ranked it as their preferred agent. Use of SDM was reported by 21.6% of patients and 88.5% were unaware that multiple P2Y. Significant differences exist between cardiology-providers and patients regarding factors influencing P2Y

Topics: Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Humans; Patient Preference; Patient Selection; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

Patients with atrial fibrillation undergoing coronary intervention are at higher bleeding risk due to the concomitant need for oral anticoagulation and antiplatelet therapy. The RE-DUAL PCI trial demonstrated better safety with dual antithrombotic therapy (DAT: dabigatran 110 or 150 mg b.i.d., clopidogrel or ticagrelor) compared to triple antithrombotic therapy (TAT: warfarin, clopidogrel or ticagrelor, and aspirin). We explored the impact of baseline bleeding risk based on the PRECISE-DAPT score for decision-making regarding DAT vs. TAT.. A score ≥25 points qualified high bleeding risk (HBR). Comparisons were made for the primary safety endpoint International Society of Thrombosis and Haemostasis major or clinically relevant non-major bleeding, and the composite efficacy endpoint of death, thrombo-embolic events, or unplanned revascularization, analysed by time-to-event analysis. PRECISE-DAPT was available in 2336/2725 patients, and 37.9% were HBR. Compared to TAT, DAT with dabigatran 110 mg reduced bleeding risk both in non-HBR [hazard ratio (HR) 0.42, 95% confidence interval (CI) 0.31-0.57] and HBR (HR 0.70, 95% CI 0.52-0.94), with a greater magnitude of benefit among non-HBR (Pint = 0.02). Dual antithrombotic therapy with dabigatran 150 mg vs. TAT reduced bleeding in non-HBR (HR 0.60, 95% CI 0.45-0.80), with a trend toward less benefit in HBR patients (HR 0.92, 95% CI 0.63-1.34; Pint = 0.08). The risk of ischaemic events was similar on DAT with dabigatran (both 110 and 150 mg) vs. TAT in non-HBR and HBR patients (Pint = 0.45 and Pint = 0.56, respectively).. PRECISE-DAPT score appeared useful to identify AF patients undergoing PCI at further increased risk of bleeding complications and may help clinicians identifying the antithrombotic regimen intensity with the best benefit-risk ratio in an individual patient.

Topics: Anticoagulants; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor

This study aimed to evaluate and compare the effectiveness and safety between clopidogrel and ticagrelor in acute coronary syndrome (ACS) with renal dysfunction.. We conducted a retrospective cohort study on patients on chronic dialysis and whose admission diagnosis between 1 July 2013 and 31 December 2016 included ACS. The primary effectiveness endpoint was a major adverse cardiovascular event (MACE), and the primary safety endpoint was a major bleeding event. The application of propensity scores through the inverse probability of treatment weighting (IPTW) was applied to the study groups. Cox regression was used to estimate hazard ratios (aHRs) of study endpoints. In addition, the competing risk was adjusted using the Fine and Gray competing risk model.. There were 1915 patients in the clopidogrel group and 270 patients in the ticagrelor group. At 12 months, the ticagrelor group had higher risks for MACE (aHR with IPTW: 1.29; 95% CI 1.16-1.44); death (aHR with IPTW: 1.65; 95% CI 1.47-1.86) and cardiac death (subdistribution HR [SHR] with IPTW: 1.64; 95% CI 1.41-1.91), compared with those in the clopidogrel group. For major bleeding event, the risk was significantly higher with ticagrelor than with clopidogrel (SHR with IPTW: 1.49; 95% CI 1.34-1.65). In terms of the risk for any bleeding event, there was no significant difference between the two groups (SHR with IPTW: 1.05; 95% CI 0.95-1.17).. Compared with clopidogrel, ticagrelor was associated with higher MACE, death, cardiac death and major bleeding risk within 12 months in patients with ACS and on dialysis.

Topics: Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Renal Dialysis; Retrospective Studies; Taiwan; Ticagrelor; Treatment Outcome

 This article compares the clinical outcomes of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS) without cytochrome P450 (CYP)2C19 loss-of-function (LOF) alleles and investigates whether clopidogrel could be an alternative P2Y12 inhibitor without increasing the risk of ischemic events..  Patients were divided into the clopidogrel-treated group and the ticagrelor-treated group. Inverse probability of treatment weighting (IPTW) calculated by propensity scores was used to adjust confounding covariates. The primary outcome was major adverse cardiovascular or cerebrovascular events (MACCEs) within 12 months. The secondary outcomes were MACCEs plus unstable angina, and clinically significant bleeding events..  Finally, 2,199 patients were included. Of them, 1,606 were treated with clopidogrel, and 593 were treated with ticagrelor. The mean age of the original cohort was 59.92 ± 9.81 years. During the 12-month follow-up period, MACCEs occurred in 89 patients (4.0%). No significant differences were observed in MACCEs (IPTW-adjusted hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.65-1.18), MACCEs plus unstable angina (IPTW-adjusted HR, 1.20; 95% CI, 0.91-1.59), or clinically significant bleeding events (IPTW-adjusted HR, 0.81; 95% CI, 0.53-1.23) between the clopidogrel- and ticagrelor-treated groups..  In patients with ACS without CYP2C19 LOF alleles, clopidogrel was not associated with a higher risk of MACCEs when compared with ticagrelor. The main findings of this study support use of clopidogrel in CYP2C19 LOF noncarriers as an alternative P2Y12 inhibitor, which may reduce medical expenses and adverse reactions caused by more potent P2Y12 inhibitors in these patients.

Topics: Acute Coronary Syndrome; Aged; Alleles; Angina, Unstable; Clopidogrel; Cytochrome P-450 CYP2C19; Hemorrhage; Humans; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Although ticagrelor is known to increase the bleeding risk compared to clopidogrel in East Asian patients, its clinical benefits in patients with acute myocardial infarction (AMI) without high bleeding risk (HBR) remains unknown.. A total of 7,348 patients who underwent successful percutaneous coronary intervention (PCI) from the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH), between November 2011 and December 2015, were divided into two groups according to the Academic Research Consortium for HBR criteria (KAMIR-HBR, 2,469 patients; KAMIR-non HBR, 4,879 patients). We compared in-hospital major adverse cardiovascular events (MACEs, defined as a composite of cardiac death, non-fatal myocardial infarction, or stroke), and the thrombolysis in myocardial infarction (TIMI) major bleeding between ticagrelor and clopidogrel in the KAMIR-HBR and the KAMIR-non HBR groups, respectively.. After propensity score matching, ticagrelor had a higher incidence of in-hospital TIMI major bleeding than clopidogrel in all patients (odds ratio [OR], 1.683; 95% confidence interval [CI], 1.010-2.805;. The bleeding risk of ticagrelor was attenuated in Korean patients with AMI without HBR. Appropriate patient selection could reduce in-hospital bleeding complications associated with ticagrelor in Korean patients with AMI who underwent successful PCI.

Topics: Acute Disease; Aged; Clopidogrel; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Propensity Score; Purinergic P2Y Receptor Antagonists; Registries; Republic of Korea; Risk; Ticagrelor; Treatment Outcome

Hemorrhagic complications are often reported following antiplatelet therapy; however, simultaneous multifocal hemorrhages in both legs are uncommon. The patient was a 75-year-old man diagnosed with ST elevation myocardial infarction who underwent percutaneous coronary intervention in the right coronary artery. He was prescribed oral acetylsalicylic acid and ticagrelor. Three days after initial drug treatment, he complained of bilateral leg pain that was aggravated by walking and moving his ankle across a broad range of motion. No deep vein thrombosis was detected on Doppler ultrasonography; however, muscular hemorrhage was suspected according to musculoskeletal ultrasonography. Multifocal muscular hemorrhage was confirmed in the soleus and gastrocnemius muscles on magnetic resonance imaging. To reduce the risk of bleeding, we changed the medication from ticagrelor to clopidogrel. The patient performed leg elevation exercises, compression, and applied an ice pack. He also performed range of motion exercises and gait training in addition to receiving drug treatment. With these therapies, his pain score improved from 5 to 3 on a visual analog scale, without further complications. Multifocal muscular hemorrhage rarely occurs bilaterally; however, when it does occur, an appropriate treatment plan can be developed based on musculoskeletal ultrasonography.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Hemorrhage; Humans; Leg; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Optimal dual antiplatelet therapy (DAPT) strategy in high-bleeding risk (HBR) patients presenting with acute coronary syndrome remains debated. We sought to investigate the use of clopidogrel versus ticagrelor in HBR patients with acute coronary syndrome and their impact on ischemic and bleeding events at 1 year. In the START-ANTIPLATELET registry (NCT02219984), consecutive patients with ≥ 1 HBR criteria were stratified by DAPT type in clopidogrel versus ticagrelor groups. The primary endpoint was net adverse clinical endpoints (NACE), defined as a composite of all-cause death, myocardial infarction, stroke, and major bleeding. Of 1209 patients with 1-year follow-up, 553 were defined at HBR, of whom 383 were considered eligible for the study as on DAPT with clopidogrel (174 or 45.4%) or ticagrelor (209 or 54.6%). Clopidogrel was more often administered in patients at increased ischemic and bleeding risk, while ticagrelor in those undergoing percutaneous coronary intervention. Mean DAPT duration was longer in the ticagrelor group. At 1 year, after multivariate adjustment, no difference in NACEs was observed between patients on clopidogrel versus ticagrelor (19% vs. 11%, adjusted hazard ratio 1.27 [95% CI 0.71-2.27], p = 0.429). Age, number of HBR criteria, and mean DAPT duration were independent predictors of NACEs. In a real-world registry of patients with acute coronary syndrome, 45% were at HBR and frequently treated with clopidogrel. After adjustment for potential confounders, the duration of DAPT, but not DAPT type (stratified by clopidogrel vs. ticagrelor), was associated with the risk of ischemic and bleeding events at 1 year.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Cause of Death; Clopidogrel; Female; Hemorrhage; Humans; Italy; Male; Platelet Aggregation Inhibitors; Prospective Studies; Registries; Risk; Ticagrelor

Topics: Aged; China; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Propensity Score; Prospective Studies; ST Elevation Myocardial Infarction; Ticagrelor

Despite recommendations for standardized preoperative waiting of at least 3, 5, and 7 days for ticagrelor, clopidogrel, and prasugrel, respectively, there is still substantial interinstitutional variation in preoperative discontinuation of dual antiplatelet therapy in patients needing coronary artery bypass grafting (CABG).. In 299 patients undergoing CABG with or without valve intervention less than 7 days after last P2Y. A total of 83% of patients underwent CABG less than 48 hours after last drug intake. Calculated blood loss was lower in patients taking clopidogrel as compared with prasugrel or ticagrelor (1063 mL [690 to 1394 mL] vs 1351 mL [876 to 1829 mL] vs 1330 mL [994 to 1691 mL]; P < .001). Overall, 135 (45%) patients sustained BARC-4 bleeding; the incidence differed among the groups (P = .015) and was significantly higher in prasugrel-treated patients, as compared with clopidogrel-treated patients. In multivariable linear regression analysis, European System for Cardiac Operative Risk Evaluation II (EuroSCORE II), aspirin dose, cardiopulmonary bypass time, drug withdrawal time, and type of P2Y. Exposure to prasugrel and ticagrelor 24 hours or less before CABG increases both calculated blood loss and BARC-4 bleeding as compared with clopidogrel. Although discontinuation for longer than 48 hours substantially reduced calculated blood loss and BARC-4 bleeding across all P2Y

Topics: Aged; Clopidogrel; Coronary Artery Bypass; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Preoperative Period; Prospective Studies; Purinergic P2Y Receptor Antagonists; Ticagrelor; Time Factors; Withholding Treatment

Ticagrelor improves clinical outcomes in patients with acute myocardial infarction (AMI). This study aimed to compare the efficacy and safety of ticagrelor vs. clopidogrel in East Asian patients with AMI. Between July 2013 and December 2015, patients with AMI prescribed dual antiplatelet therapy were identified from the National Health Insurance Research Database of Taiwan. Using propensity score weighting, ticagrelor was compared with clopidogrel for the primary efficacy end point (a composite of all-cause death, myocardial infarction (MI), and stroke) and bleeding. A total of 32,442 patients with AMI (ticagrelor: 10,057; clopidogrel: 22,385) were eligible for analysis. After propensity score weighting, ticagrelor was comparable to clopidogrel in the incidence rate of the primary efficacy end point (23.6 vs. 22.76/100 patient-years; hazard ratio (HR) 0.97; 95% confidence interval (CI) 0.89-1.06; P = 0.513). Ticagrelor was associated with a lower risk of stroke (1.78 vs. 2.66/100 patient-years; HR 0.64; 95% CI 0.49-0.85; P = 0.002) and higher risks of overall (21.59 vs. 18.35/100 patient-years; HR 1.16; 95% CI 1.06-1.27; P = 0.002) and Bleeding Academic Research Consortium (BARC) type 2 bleeding (18.67 vs. 15.08/100 patient-years; HR 1.22; 95% CI 1.11-1.36; P < 0.001). The risks of death, MI, and BARC 3 or 5 bleeding were comparable between ticagrelor and clopidogrel. In the present study, ticagrelor was comparable to clopidogrel in the composite of death, MI, and stroke, but had an increased risk of BARC type 2 bleeding. Ticagrelor may be beneficial in preventing post-MI stroke in East Asian patients.

Topics: Aged; Asian People; Clopidogrel; Cohort Studies; Data Management; Female; Hemorrhage; Humans; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Propensity Score; Stroke; Taiwan; Ticagrelor; Treatment Outcome

A strong association between on-thienopyridine platelet reactivity (PR) and the risk of both thrombotic and bleeding events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) has been demonstrated. However, no study has analyzed the relationship between on-ticagrelor PR and clinical outcome in this clinical setting.. We aimed to investigate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein (VASP) index, and clinical outcome in patients with ACS undergoing PCI.. We performed a prospective, multicenter, observational study of patients undergoing PCI for ACS. PR was measured using the VASP index following ticagrelor loading dose. The primary study endpoint was the rate of Bleeding Academic Research Consortium (BARC) type ≥2 at 1 year. The key secondary endpoint was the rate of major adverse cardiovascular events (MACE) defined as the composite of cardiovascular death, myocardial infarction, stroke, and urgent revascularization.. We included 570 ACS patients, among whom 33.9% had ST-elevation myocardial infarction. BARC type ≥2 bleeding occurred in 10.9% and MACE in 13.8%. PR was not associated with BARC ≥2 or with MACE (. On-ticagrelor PR measured by the VASP was not associated with bleeding or thrombotic events in ACS patients undergoing PCI. PR measured by the VASP should not be used as a surrogate endpoint in studies on ticagrelor.

Topics: Acute Coronary Syndrome; Aged; Blood Platelets; Cell Adhesion Molecules; Female; Hemorrhage; Humans; Male; Microfilament Proteins; Middle Aged; Percutaneous Coronary Intervention; Phosphoproteins; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Topics: Hemorrhage; Humans; Myocardial Infarction; Ticagrelor

Major adverse cardiac event (MACE) and bleeding risks following percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) are not well defined in individuals with heart failure (HF). We followed 1,145 individuals in the Pharmacogenomic Resource to improve Medication Effectiveness Genotype Guided Antiplatelet Therapy cohort for MACE and bleeding events following PCI for ACS. We constructed Cox proportional hazards models to compare MACE and bleeding in those with versus without HF, adjusting for sociodemographics, comorbidities, and medications. We also determined predictors of MACE and bleeding events in both groups. 370 (32%) individuals did and 775 (68%) did not have HF prior to PCI. Mean age was 61.7 ± 12.2 years, 31% were female, and 24% were African American. After a median follow-up of 0.78 years, individuals with HF had higher rates of MACE compared to those without HF (48 vs. 24 events per 100 person years) which remained significant after multivariable adjustment (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.00 to 1.72). Similarly, bleeding was higher in those with versus without HF (22 vs. 11 events per 100 person years), although this was no longer statistically significant after multivariable adjustment (HR 1.29, 95% CI 0.86 to 1.93). Diabetes and peripheral vascular disease were predictors of MACE, and end-stage renal disease was a predictor of bleeding among participants with HF. MACE risk is higher in individuals with versus without HF following PCI for ACS. However, the risk of bleeding, especially among those with end-stage renal disease , must be considered when determining post-PCI anticoagulant strategies.

Topics: Acute Coronary Syndrome; Aged; Angina, Unstable; Aspirin; Case-Control Studies; Clopidogrel; Diabetes Mellitus; Dual Anti-Platelet Therapy; Female; Heart Failure; Hemorrhage; Hospitalization; Humans; Ischemic Attack, Transient; Ischemic Stroke; Kidney Failure, Chronic; Male; Middle Aged; Mortality; Multivariate Analysis; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Proportional Hazards Models; Risk Factors; ST Elevation Myocardial Infarction; Stroke Volume; Ticagrelor; Treatment Outcome

The comparative efficacy and safety of prasugrel and ticagrelor in patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) remain unclear. We aimed to investigate the association of treatment with clinical outcomes.. In the SWEDEHEART (Swedish Web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies) registry, all patients with MI treated with PCI and discharged on prasugrel or ticagrelor from 2010 to 2016 were included. Outcomes were 1-year major adverse cardiac and cerebrovascular events (MACCE, death, MI or stroke), individual components and bleeding. Multivariable adjustment, inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were used to adjust for confounders.. We included 37 990 patients, 2073 in the prasugrel group and 35 917 in the ticagrelor group. Patients in the prasugrel group were younger, more often admitted with ST elevation MI and more likely to have diabetes. Six to twelve months after discharge, 20% of patients in each group discontinued the P2Y12 receptor inhibitor they received at discharge. The risk for MACCE did not significantly differ between prasugrel-treated and ticagrelor-treated patients (adjusted HR 1.03, 95% CI 0.86 to 1.24). We found no significant difference in the adjusted risk for death, recurrent MI or stroke alone between the two treatments. There was no significant difference in the risk for bleeding with prasugrel versus ticagrelor (2.5% vs 3.2%, adjusted HR 0.92, 95% CI 0.69 to 1.22). IPTW and PSM analyses confirmed the results.. In patients with MI treated with PCI, prasugrel and ticagrelor were associated with similar efficacy and safety during 1-year follow-up.

Topics: Aged; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Patient Discharge; Percutaneous Coronary Intervention; Postoperative Complications; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Stroke; Sweden; Ticagrelor; Treatment Outcome

The PEGASUS-TIMI 54 trial inclusion criteria effectively identified high-risk patients with recent myocardial infarction (MI) who would benefit from continuing dual antiplatelet therapy (DAPT) with ticagrelor for more than 12 months. It is unknown how many real-world patients meet these criteria during the acute phase of ST-elevation MI (STEMI), or the extent to which these criteria predict a patient's risk and prognosis. Study objectives were: (1) determine the proportion of PEGASUS-TIMI 54-like patients (PG-l) in a real-world cohort of patients hospitalized with STEMI and to assess their ischemic and hemorrhagic risk; (2) examine their ischemic and hemorrhagic in-hospital events (major adverse cardiovascular and cerebrovascular events [MACCE] and clinically relevant bleeding); (3) evaluate their long-term outcomes and the impact on the long-term prognosis of the type of DAPT prescribed at discharge.. This observational study was conducted in 1086 patients admitted to hospital with a diagnosis of STEMI between February 2011 and March 2018 and enrolled in the CARDIO-STEMI Sanremo registry. Patients' demographic and clinical characteristics, procedural variables, and individual ischemic and hemorrhagic risk scores were assessed in-hospital. Four-year survival was also analyzed.. The proportion of PG-I patients was 69.2%. Compared with non-PG-l patients, PG-l patients were older, had more multivessel disease and comorbidities, and experienced more frequent MACCE (8.3% vs. 3.6%, p = 0.005) and clinically significant bleeding events (6.7% vs. 2.7%, p = 0.008), a higher rate of in-hospital death (6.5% vs. 1.5%, p < 0.001), and higher follow-up mortality rate (14.8% vs. 7.7%; p = 0.002). Four-year survival was significantly lower in the PG-l group (83.9% vs. 91.8%; Log-rank = 0.001) and was related to the cumulative number of concurrent risk factors. In the unadjusted analysis, survival was greater in patients discharged on ticagrelor than on another P2Y. The risk of MACCE for PG-l patients increased with the number of concurrent PEGASUS-TIMI 54 risk features. Treatment with ticagrelor on discharge was associated with improved survival rates during 4 years of follow-up.

Topics: Aged; Aspirin; Clinical Decision-Making; Clinical Trials as Topic; Drug Administration Schedule; Dual Anti-Platelet Therapy; Female; Hemorrhage; Hospital Mortality; Humans; Italy; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; Registries; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Treatment Outcome

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Cause of Death; Clopidogrel; England; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Survival Rate; Ticagrelor

Higher risk of bleeding with ticagrelor over clopidogrel in elderly patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) has been suggested. We assessed the incidence of major bleedings (MB), reinfarction (re-MI), and all-cause death to evaluate safety and efficacy of ticagrelor versus clopidogrel in such population.. Real-world registries RENAMI and BleeMACS were merged. The pooled cohort was divided into two groups, clopidogrel versus ticagrelor. Statistical analysis considered patients <75 versus ≥75 years old. Endpoints were BARC 3-5 MB, re-MI, and all-cause death at 1-year follow-up. The study included 16,653 patients (13,153 < 75 and 3500 ≥ 75 years). Ticagrelor was underused in elderly patients (16.3% versus 20.8%, P < 0.001). Using propensity score matching (PSM), two treatment groups of 1566 patients were included in the final analysis.. Ticagrelor was able to prevent re-MI (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.2-0.6; P < 0.001) and all-cause death (HR, 0.60; 95% CI, 0.4-0.9; P = 0.026) irrespective of age. In patients ≥75 years, ticagrelor reduced all-cause death (HR, 0.32; 95% CI, 0.1-0.8; P = 0.012) and re-MI (HR, 0.25; 95% CI, 0.1-1.1, P = 0.072). Moreover, even with the limit of the low number of events, ticagrelor did not significantly increase the incidence of MB (HR, 1.49; 95% CI, 0.70-3.0; P = 0.257). At multiple Cox regression, age (HR, 1.03; 95% CI, 1.02-1.05; P < 0.001) resulted an independent risk factor for bleeding.. In our study, reflecting the results from two large retrospective, real-world registries, Ticagrelor did not significantly increase MB compared with clopidogrel in elderly patients with ACS treated with PCI, while significantly improving 1-year survival. Further studies on elderly patients are suggested.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Clopidogrel; Female; Hemorrhage; Humans; Male; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Propensity Score; Registries; Retrospective Studies; Ticagrelor

Ticagrelor is a part of dual antiplatelet therapy (DAPT) which has proven benefits in patients with acute coronary syndrome especially in those undergoing percutaneous coronary intervention (PCI). However, like most other drugs, it can lead to undesired and adverse effects such as dyspnoea, easy bruising and gastrointestinal bleeding. We present a case of 70-year-old woman who developed diarrhoea following initiation of DAPT comprising of aspirin and ticagrelor following PCI. After excluding more common causes, it was attributed to ticagrelor administration and completely resolved after it was replaced with another oral antiplatelet agent. On follow-up, the patient reported complete resolution of symptoms.

Topics: Acute Coronary Syndrome; Aged; Diarrhea; Female; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor

Patients on dual antiplatelet therapy following percutaneous coronary intervention often have indications for concomitant oral anticoagulation, known as triple antithrombotic therapy. Majority of literature evaluating triple antithrombotic therapy fails to adequately represent patients with ST-elevation myocardial infarction and those prescribed potent P2Y12 inhibitors, ticagrelor or prasugrel. The purpose of this study was to evaluate the safety and efficacy of triple antithrombotic regimens containing ticagrelor or prasugrel versus clopidogrel after percutaneous coronary intervention in the setting of ST-elevation myocardial infarction.. This was a single-center, retrospective cohort trial. The primary endpoint was net adverse clinical event, defined as the primary efficacy endpoint of death, myocardial infarction, or cerebrovascular accident and the primary safety endpoint of any bleeding event.. Between October 2017 and October 2019, a total of 65 patients with ST-elevation myocardial infarction were initiated on triple therapy. Forty-six patients were included in the primary analysis, of which 26 were discharged on triple antithrombotic therapy with clopidogrel and 20 discharged on potent P2Y12 inhibitors (ticagrelor or prasugrel). The primary endpoint occurred in 27% of the clopidogrel group and 40% of the potent P2Y12 inhibitor group (. This small cohort study suggests, in patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention, the net adverse clinical event rate does not differ between clopidogrel and potent P2Y12 inhibitors in the setting of triple antithrombotic therapy. The results of this exploratory analysis warrant confirmation in a larger, randomized study.

Topics: Aged; Aged, 80 and over; Clopidogrel; Cohort Studies; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Massachusetts; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Retrospective Studies; ST Elevation Myocardial Infarction; Stroke; Ticagrelor

[Figure: see text].

Topics: Acute Coronary Syndrome; Aspirin; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor

The aim of the present study was to establish the safety and efficacy profile of prasugrel and ticagrelor in real-life acute coronary syndrome (ACS) patients with renal dysfunction.. All consecutive patients from RENAMI (REgistry of New Antiplatelets in patients with Myocardial Infarction) and BLEEMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registries were stratified according to estimated glomerular filtration rate (eGFR) lower or greater than 60 mL/min/1.73 m2. Death and myocardial infarction (MI) were the primary efficacy endpoints. Major bleedings (MBs), defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety endpoint. A total of 19 255 patients were enrolled. Mean age was 63 ± 12; 14 892 (77.3%) were males. A total of 2490 (12.9%) patients had chronic kidney disease (CKD), defined as eGFR <60 mL/min/1.73 m2. Mean follow-up was 13 ± 5 months. Mortality was significantly higher in CKD patients (9.4% vs. 2.6%, P < 0.0001), as well as the incidence of reinfarction (5.8% vs. 2.9%, P < 0.0001) and MB (5.7% vs. 3%, P < 0.0001). At Cox multivariable analysis, potent P2Y12 inhibitors significantly reduced the mortality rate [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.54-0.96; P = 0.006] and the risk of reinfarction (HR 0.53, 95% CI 0.30-0.95; P = 0.033) in CKD patients as compared to clopidogrel. The reduction of risk of reinfarction was confirmed in patients with preserved renal function. Potent P2Y12 inhibitors did not increase the risk of MB in CKD patients (HR 1.00, 95% CI 0.59-1.68; P = 0.985).. In ACS patients with CKD, prasugrel and ticagrelor are associated with lower risk of death and recurrent MI without increasing the risk of MB.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Female; Glomerular Filtration Rate; Hemorrhage; Humans; Kidney; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Recurrence; Registries; Renal Insufficiency, Chronic; Retrospective Studies; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Real-life data comparing clopidogrel, prasugrel, and ticagrelor for unselected patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are lacking, as are data for the temporal distribution of ischemic and bleeding risks.. A total of 19,825 patients were enrolled from the RENAMI and BleeMACS registries. Both were multicenter, retrospective, observational registries including the data and outcomes of consecutive patients with ACS who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT). We evaluated the long-term outcome stratified by the different antiplatelet agents.. A total of 14,105 patients (71.2%) were treated with clopidogrel, 2364 patients (11.9%) with prasugrel and 3356 patients (16.9%) with ticagrelor. After propensity score matching, at 1 year, prasugrel reduced the incidence of net adverse clinical events (NACE; a composite endpoint of all-cause death, myocardial infarction [MI] and Bleeding Academic Research Consortium [BARC] 3-5 bleeding) (4.2% vs.7.6%, p = 0.002) and of major adverse cardiovascular events (MACE; a composite endpoint of death and MI) compared with clopidogrel (2.6% vs. 5.2%, p = 0.007). Ticagrelor decreased rates of MACE compared with clopidogrel (2.7% vs. 6.2%, p < 0.001), but not of NACE (6.6% vs. 8.7%, p = 0.07). Ticagrelor presented similar performance in terms of MACE compared with prasugrel (2.8% vs. 2.4%, p = 0.56), with a trend towards a reduction in MI (0.2% vs. 0.4%, p = 0.56), but with higher risk of BARC 3-5 bleedings (3.8% vs. 1.7%, p = 0.04). In the daily risk analysis, clopidogrel presented a binomial distribution with a peak of ischemic risk at 3 months, which decreased towards bleedings; prasugrel had a constant equivalence between opposite risks; and ticagrelor constantly reduced recurrent MIs despite higher risk of BARC 3-5 events.. In real life, ticagrelor is more effective in reducing ischemic events during the first year after ACS, despite an increased risk of major bleedings, while prasugrel assures a better balance between ischemic and bleeding recurrent events.

Topics: Acute Coronary Syndrome; Clopidogrel; Europe; Female; Hemorrhage; Humans; Male; Medication Therapy Management; Middle Aged; Mortality; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Registries; Risk Adjustment; Therapeutic Equivalency; Ticagrelor

Patients treated with ticagrelor and aspirin usually suffer from bleeding events, especially mild bleeding which is one of the main factors reducing patients' adherence to ticagrelor. The objective of this study is to investigate the efficacy and safety of ticagrelor combined with a lower dose of aspirin (50 mg) than that recommended by guidelines (75-100 mg). In this study, we prospectively enrolled 1220 patients who take ticagrelor in the hospital. After excluding the patients who did not take ticagrelor after discharge or lost to follow-up, the remaining 1066 patients were divided into two aspirin dose groups: 75-100 mg (

Topics: Aspirin; Coronary Artery Disease; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Ticagrelor

Use of oral antiplatelets (OAPs) is essential for preventing thrombotic events in patients with acute coronary syndrome (ACS). Effects of clopidogrel, prasugrel, and ticagrelor may be enhanced due to pharmacodynamic interactions, but as CYP substrates, they are prone to pharmacokinetic interactions too. The aim was to study polypharmacy in ACS patients following hospital discharge.. This observational drug utilization study linked patient-level data from nationwide registers. The study population consisted of adult ACS patients discharged from Finnish hospitals in 2009-2013. Logistic regression was used to model the probability of drug-drug interactions with odd ratios for predefined predictors such as age, gender, and ACS type.. In the cohort of 54,416 ACS patients, 91% of those treated with OAP received clopidogrel. Of clopidogrel-treated patients, 12% purchased warfarin at least once while on clopidogrel treatment. Old age, male sex, ST-elevation myocardial infarction as index event, and a history of previous ACS events were associated with an increased risk of warfarin-OAP interaction (p < 0.001 for all). Ibuprofen, and serotonergic drugs tramadol, citalopram, and escitalopram were the next most common drugs causing pharmacodynamic interactions. In general, concomitant use of drugs known to cause pharmacokinetic interactions was rare, but both esomeprazole and omeprazole were prescribed in more than 6% of clopidogrel-treated patients.. Warfarin and ibuprofen were the most commonly used concomitant medications causing pharmacodynamic interactions and potentially increasing the risk of bleeding in OAP-treated patients. Esomeprazole and omeprazole were used in clopidogrel-treated patients although there are alternatives available for gastric protection.

Topics: Acute Coronary Syndrome; Administration, Oral; Adult; Aged; Clopidogrel; Cohort Studies; Drug Interactions; Female; Finland; Hemorrhage; Humans; Male; Middle Aged; Outpatients; Platelet Aggregation Inhibitors; Polypharmacy; Prasugrel Hydrochloride; Retrospective Studies; Ticagrelor

The risk of recurrent ischemia and bleeding after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) may vary during the first year of follow-up according to clinical presentation, and medical and interventional strategies.. BleeMACS and RENAMI are 2 multicenter registries enrolling patients with ACS treated with PCI and clopidogrel, prasugrel, or ticagrelor. The average daily ischemic and bleeding risks (ADIR and ADBR) in the first year after PCI were the primary end points. The difference between ADBR and ADIR was calculated to estimate the potential excess of bleeding/ischemic events in a given period or specific subgroup.. A total of 19,826 patients were included. Overall, in the first year after PCI, the ADBR was 0.008085%, whereas ADIR was 0.008017% (P = .886). In the first 2 weeks ADIR was higher than ADBR (P = .013), especially in patients with ST-segment elevation myocardial infarction or incomplete revascularization. ADIR continued to be, albeit non-significantly, greater than ADBR up to the third month, whereas ADBR became higher, although not significantly, afterward. Patients with incomplete revascularization had an excess in ischemic risk (P = .003), whereas non-ST-segment elevation ACS patients and those on ticagrelor had an excess of bleeding (P = .012 and P = .022, respectively).. In unselected ACS patients, ADIR and ADBR occurred at similar rates within 1 year after PCI. ADIR was greater than ADBR in the first 2 weeks, especially in ST-segment elevation myocardial infarction patients and those with incomplete revascularization. In the first year, ADIR was higher than ADBR in patients with incomplete revascularization, whereas ADBR was higher in non-ST-segment elevation ACS patients and in those discharged on ticagrelor.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Female; Hemorrhage; Humans; Ischemia; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Prasugrel Hydrochloride; Recurrence; Registries; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors

Topics: Clopidogrel; Coronary Artery Bypass; Hemorrhage; Humans; Ticagrelor

The clinical efficacy of ticagrelor is questionable in East Asian populations. Patients with acute myocardial infarction (AMI) with multivessel disease (MVD) are considered as high risk patients who might benefit from ticagrelor treatment. The purpose of this study is to compare the clinical effect of ticagrelor and clopidogrel in AMI patients with MVD in Korea.. A total of 2275 patients between November 2011 and June 2015, diagnosed with AMI with MVD after successful percutaneous coronary intervention who were registered in the Korea Acute Myocardial Infarction Registry - National Institute of Health (KAMIR-NIH) were enrolled. Patients were divided into ticagrelor (n = 837) and clopidogrel group (n = 1438). The primary endpoint was major adverse cardiac events (MACE) defined as cardiac death, non-fatal MI, target vessel revascularization, or ischemic stroke during 2 years of clinical follow-up. Secondary endpoints were thrombolysis in myocardial infarction (TIMI) major or minor bleeding, net clinical event composed of MACE and TIMI major bleeding, any repeated percutaneous coronary intervention, heart failure requiring re-hospitalization, and stent thrombosis. After propensity score matching analysis, the primary endpoint was lower in ticagrelor group compared to the clopidogrel group (8.6 % vs. 11.9 %; HR: 0.68; 95 % CI: 0.50-0.94; p = 0.018). The risk of TIMI major or minor bleeding was higher in the ticagrelor group (10.8 % vs. 4.8 %; HR: 2.51; 95 % CI: 1.68-3.76; p < 0.001). The net clinical event was similar between ticagrelor and clopidogrel group (11.3 % vs. 13.6 %; HR 0.82; 95 % CI: 0.60-1.11; p = 0.195).. Ticagrelor significantly reduced the risk of MACE than clopidogrel for AMI patients with MVD in Korea. However, the risk of TIMI major or minor bleeding was higher and the net clinical benefit was similar. Further large-scale multi-center randomized clinical trials are needed to clarify the proper use dual antiplatelet therapy in East Asian populations.

Topics: Aged; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Registries; Republic of Korea; Thrombolytic Therapy; Ticagrelor; Treatment Outcome

Topics: Acute Coronary Syndrome; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Recurrence; Risk Assessment; Risk Factors; Stents; Ticagrelor; Treatment Outcome

The RE-DUAL PCI trial reported that dabigatran dual therapy (110/150 mg twice daily, plus clopidogrel or ticagrelor) reduced bleeding events versus warfarin triple therapy (warfarin plus aspirin and clopidogrel or ticagrelor) in patients with atrial fibrillation who underwent percutaneous coronary intervention, with noninferiority in composite thromboembolic events. In this prespecified analysis, risks of first major or clinically relevant nonmajor bleeding event and composite end point of death, thromboembolic events, or unplanned revascularization were compared between dabigatran dual therapy and warfarin triple therapy in older (≥ 75 years) and younger (< 75 years) patients, using Cox proportional hazard regression. Of 2,725 patients randomized to treatment, 1,026 (37.7%) were categorized into older and 1,699 (62.3%) into younger age groups. Dabigatran 110 mg dual therapy lowered bleeding risk versus warfarin triple therapy in older (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.51 to 0.89) and younger patients (HR 0.40; 95% CI 0.30 to 0.54); interaction p value: 0.0125. Dabigatran 150 mg dual therapy lowered bleeding risk versus warfarin triple therapy in younger patients (HR 0.57; 95% CI 0.44 to 0.74), whereas no benefit could be observed in older patients (HR 1.21; 95% CI 0.83 to 1.77); interaction p value: 0.0013. For the thromboembolic end point, there was a trend for a higher risk with dabigatran 110 mg dual therapy in older patients, compared with warfarin triple therapy, whereas the risk was similar in younger patients. For dabigatran 150 mg dual therapy, the thromboembolic risk versus warfarin triple therapy was similar in older and younger patients. In conclusion, the benefits of dabigatran dual therapy differed in the 2 age groups, which may help dose selection when using dabigatran dual therapy.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Revascularization; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Stroke; Thromboembolism; Ticagrelor; Treatment Outcome; Warfarin

Guidelines currently recommend ticagrelor over clopidogrel for patients with acute coronary syndrome (ACS) based on randomized clinical trial data in which ticagrelor reduced major adverse coronary events (MACE) vs clopidogrel but increased bleeding and dyspnea.. To compare the risk of MACE with ticagrelor vs clopidogrel in patients with ACS treated with percutaneous coronary intervention (PCI), to compare major bleeding and dyspnea, and to evaluate the association between P2Y12 inhibitor adherence and MACE.. Population-based cohort study using data of patients discharged alive after PCI for ACS from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry from April 1, 2012, to March 31, 2016, with follow-up to 1 year. Analysis began April 2018.. Outpatient prescription for ticagrelor or clopidogrel within 31 days after PCI. Adherence was defined as a medication refill adherence value of 80% or higher.. Major adverse coronary events, a composite of all-cause death, hospitalization for ACS, unplanned coronary revascularization, or stent thrombosis within 365 days after index PCI. Secondary outcomes included hospitalization for major bleeding and emergency department visit for dyspnea.. Of 11 185 individuals who underwent PCI, the median (interquartile range) age was 61 (54-71) years, and 2760 (24.7%) were women. Ticagrelor users (4076 [36.4%]) were generally younger and had fewer cardiac and noncardiac comorbidities than clopidogrel users. Ticagrelor was not associated with lower risk of MACE (adjusted hazard ratio [aHR], 0.97; 95% CI, 0.85-1.10); however, it was associated with an increased risk of major bleeding (aHR, 1.51; 95% CI, 1.29-1.78) and dyspnea (aHR, 1.98; 95% CI, 1.47-2.65). A total of 3328 ticagrelor users (81.6%) were adherent during the study vs 5256 of clopidogrel users (73.9%) (P < .001; χ2 = 86.4). In the full cohort, adherence was associated with a lower MACE risk (aHR, 0.79; 95% CI, 0.69-0.90 for adherence of ≥80% vs <80%). Differences in other secondary outcomes were not statistically significant. Sensitivity and subgroup analyses were consistent with primary analyses.. In this population-based cohort study of patients with ACS who underwent PCI, outpatient use of ticagrelor was not associated with a statistically significant reduction in MACE vs clopidogrel; however, it was associated with more major bleeding and dyspnea.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Clopidogrel; Dyspnea; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor; Treatment Outcome

Topics: Aspirin; Coronary Artery Disease; Diabetes Mellitus, Type 2; Hemorrhage; Humans; Ticagrelor

Topics: Aspirin; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor

Bleeding risk stratification is an unresolved issue in older adults. Anemia may reflect subclinical blood losses that can be exacerbated after percutaneous coronary intervention . We sought to prospectively determine the contribution of anemia to the risk of bleeding in 448 consecutive patients aged 75 or more years, treated by percutaneous coronary interventions without concomitant indication for oral anticoagulation. We evaluated the effect of WHO-defined anemia on the incidence of 1-year nonaccess site-related major bleeding. The prevalence of anemia was 39%, and 13.1% of anemic and 5.2% of nonanemic patients suffered a bleeding event (hazard ratio 2.75, 95% confidence interval 1.37 to 5.54, p = 0.004). Neither PRECISE-DAPT nor CRUSADE scores were superior to hemoglobin for the prediction of bleeding. In conclusion, anemia is a powerful predictor of bleeding with potential utility for simplifying tailoring therapies.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anemia; Angina, Unstable; Anticoagulants; Antithrombins; Aspirin; Cause of Death; Clopidogrel; Comorbidity; Coronary Artery Disease; Drug-Eluting Stents; Female; Gastrointestinal Hemorrhage; Hemorrhage; Heparin; Hirudins; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Care; Postoperative Hemorrhage; Prasugrel Hydrochloride; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Risk Assessment; Stents; Ticagrelor; Urologic Diseases

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Cause of Death; Clinical Trials, Phase IV as Topic; Clopidogrel; Hemorrhage; Humans; Multicenter Studies as Topic; Non-ST Elevated Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Patients with coronary chronic total occlusion (CTO) require effective antiplatelet therapy after percutaneous coronary intervention (PCI). Ticagrelor has more pronounced platelet inhibition than clopidogrel. However, the most appropriate dose of ticagrelor in East Asian populations remains unclear.. We compared ticagrelor (180 mg loading dose, 90 mg twice daily thereafter and 120 mg loading dose, 60 mg twice daily thereafter) and clopidogrel (300 mg loading dose, 75 mg daily thereafter) for prevention of cardiovascular events in 525patients with CTO undergoing PCI.. The rate of in-hospital major adverse cardiac and cerebral events (MACCE) was not different between the groups. At 1-year follow-up, target vessel revascularization (TVR) in both ticagrelor groups were significantly lower than that in the clopidogrel group (p = 0.047); TVR was significantly decreased in 60 mg ticagrelor compared to standard dose clopidogrel (p = 0.046). At 1-year follow-up, overall MACCE in both ticagrelor groups were significantly lower than that in the clopidogrel group (p = 0.023). Kaplan-Meier analysis showed MACCE-free survival was significantly higher in both ticagrelor groups than in the clopidogrel group (p = 0.024). During hospitalization, minor bleeding was significant increased in the 90 mg ticagrelor group (p = 0.021). At 1-year follow-up, risk of major and minor bleeding were significantly increased in the 90 mg ticagrelor group.. In East Asian patients with CTO undergoing PCI, 60 mg ticagrelor was as effective as 90 mg, at the same time significantly reduced risk of bleeding.

Topics: Aged; Asian People; China; Chronic Disease; Clopidogrel; Coronary Occlusion; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Topics: Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Topics: Clinical Decision-Making; Clopidogrel; Coronary Thrombosis; Drug Substitution; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Treatment Outcome

To compare the risk of cardiovascular events between patients with two CYP2C19 loss-of-function alleles who were prescribed ticagrelor or clopidogrel after percutaneous coronary intervention (PCI).. Patients with two loss-of-function alleles based on the CYP2C19 genotype were selected from patients enrolled in a retrospective institutional registry. Propensity score matching using logistic regression was performed to adjust for bias between patients prescribed ticagrelor or clopidogrel. Multivariate Cox regression was used to compare the risk of adverse events in the ticagrelor and clopidogrel groups. The primary outcome was the incidence of major adverse cardiac events plus any repeat target vessel revascularization within 12 months after PCI. The safety outcomes were minor and major bleeding events.. From 1518 patients carrying two loss-of-function alleles based on the CYP2C19 genotype who underwent PCI, 638 patients treated with ticagrelor or clopidogrel were successfully propensity-score matched. The primary outcome occurred in 25 patients (7.8%) in the ticagrelor group and 47 (14.7%) in the clopidogrel group. The risk of the primary outcome was significantly lower in the ticagrelor group versus the clopidogrel group (HR 0.466, 95% CI 0.286-0.759, p = 0.002). The incidence of major bleeding events did not significantly differ between the ticagrelor and clopidogrel groups (0.3% and 0.9%, respectively), while the ticagrelor group had a higher risk of minor bleeding events (HR 1.959, 95% CI 1.396-2.750, p < 0.001).. In patients with two CYP2C19 loss-of-function alleles, ticagrelor was more effective than clopidogrel in preventing cardiovascular events, while the two antiplatelet agents were associated with similar incidences of major bleeding.

Topics: Aged; Clopidogrel; Coronary Artery Disease; Coronary Thrombosis; Cytochrome P-450 CYP2C19; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Pharmacogenomic Variants; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Stents; Ticagrelor; Time Factors; Treatment Outcome

Background Ticagrelor and prasugrel are potent P2Y12 inhibitors with superior efficacy compared with clopidogrel among patients with ST-segment-elevation myocardial infarction (STEMI), though use in recent practice is not well described. In this retrospective study, we assessed trends, predictors, and variation in use of P2Y12 inhibitors in patients with STEMI in the United States. Methods and Results We identified 169 505 STEMI patients in the Chest Pain-Myocardial Infarction Registry from October 2013 through March 2017. We determined national utilization rates of P2Y12 inhibitors at discharge, patient predictors for each medication, and variation in use between hospitals. In a subset of 9655 Medicare patients ≥65 years old, we compared 1-year adjusted risks of death, myocardial infarction, stroke, and bleeding based on hospital quartile of potent P2Y12 inhibitor use. Rates of ticagrelor use increased from 18.0% to 44.0%, while rates of prasugrel and clopidogrel use decreased from 24.6% to 13.5% and 57.4% to 42.6%, respectively. Prior percutaneous coronary intervention was the strongest clinical predictor for use of ticagrelor (adjusted odds ratio, 1.13 [95% CI, 1.09-1.18]) and prasugrel (adjusted odds ratio, 1.27 [95% CI, 1.21-1.34]) compared with clopidogrel. Predictors of clopidogrel use included no insurance, insurance with Medicare or Medicaid, and features associated with higher bleeding risk. The median hospital usage rate for newer P2Y12 inhibitors was 51.3% (interquartile range, 35.0%-65.9%), with substantial variation between hospitals (adjusted median odds ratio, 2.92 [95% CI, 2.77-3.10]). Among patients ≥65 years old, there were no differences in adjusted 1-year risks of adverse outcomes across hospital quartiles of potent P2Y12 inhibitor use. Conclusions Almost one-half of STEMI patients by 2017 were discharged on ticagrelor while far fewer received prasugrel. Patient characteristics are associated with P2Y12 inhibitor selection, though substantial hospital variation exists. Identifying barriers to use of more potent P2Y12 inhibitors may improve patient-centered decision-making for STEMI patients.

Topics: Aged; Cardiologists; Cardiology Service, Hospital; Clopidogrel; Drug Utilization; Female; Hemorrhage; Humans; Male; Middle Aged; Patient Discharge; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Registries; Retrospective Studies; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Treatment Outcome; United States

Although potent P2Y12 inhibitor-based dual antiplatelet therapy (DAPT) has replaced clopidogrel-based therapy as the standard treatment in patients with acute myocardial infarction (AMI), there is a concern about the risk of bleeding in East Asian patients. We compared the efficacy and safety of cilostazol-based triple antiplatelet therapy (TAT) with potent P2Y12 inhibitor-based DAPT in Korean patients. A total of 4152 AMI patients who underwent percutaneous coronary intervention (PCI) in the Korea Acute Myocardial Infarction Registry were analyzed retrospectively. Patients were divided into two groups: the TAT group (aspirin + clopidogrel + cilostazol, n = 3161) and the potent DAPT group (aspirin + potent P2Y12 inhibitors [ticagrelor or prasugrel], n = 991). Major clinical outcomes at 30 days and 2 years were compared between the two groups using propensity score matching (PSM) analysis. After PSM (869 pairs), there were no significant differences between the two groups in the incidence of total death, cardiac death, myocardial infarction (MI), target vessel revascularization, stent thrombosis, and stroke at 30 days and 2 years. However, the Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding rates were significantly lower in the TAT group compared with the potent DAPT group at 2 years (6.4% vs. 3.6%, p = 0.006). In Korean AMI patients undergoing PCI, TAT with cilostazol was associated with lower bleeding than the potent P2Y12 inhibitor-based DAPT without increased ischemic risk. These results could provide a rationale for the use of TAT in East Asian AMI patients.

Topics: Aged; Asian People; Aspirin; Cilostazol; Clopidogrel; Databases, Factual; Dual Anti-Platelet Therapy; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Registries; Republic of Korea; Retrospective Studies; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Intensive care unit (ICU) patients with the most severe forms of acute coronary syndrome (ACS) require invasive therapies such as extracorporeal life support. The risk of bleeding in ICU patients with ACS treated with a dual antiplatelet therapy of aspirin and ticagrelor is unknown. The primary objective of this study was to compare the bleeding risk of ticagrelor and clopidogrel in ICU patients with ACS.. We conducted a retrospective study based on a propensity score and a proportional hazards model. All patients with ACS hospitalized in the ICU of a French university hospital between January 2013 and January 2017 were included in the study. Bleeding during ICU stay was defined as all Thrombolysis in myocardial infarction (TIMI) major or minor events. A total of 155 patients were included in the study. According to propensity score matching, 57 patients treated with aspirin and ticagrelor were matched with 57 patients treated with aspirin and clopidogrel. Median (first-third quartile) Simplified Acute Physiology Score II was 61.5 (41.0-85.0). Bleeding during ICU stay occurred in 12 patients (21.1%) treated with clopidogrel and in 35 patients (61.4%) treated with ticagrelor (p<0.0001). This significant association was found for both TIMI major bleeding (12.3% vs. 35.1%, p = 0.004) and TIMI minor bleeding (8.8% vs. 26.3%, p = 0.01). The relative risk of bleeding occurrence during ICU stay was 2.60 (confidence interval 95%: 1.55-4.35) for ticagrelor compared to clopidogrel. No significant difference in ICU mortality was found between the two groups (45.6% in the clopidogrel group vs. 29.8% in the ticagrelor group, p = 0.08).. Bleeding complications are frequent and serious in ICU patients with ACS. A dual antiplatelet therapy of aspirin and ticagrelor is associated with a higher risk of bleeding compared to a dual antiplatelet therapy of aspirin and clopidogrel.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Female; Hemorrhage; Hospitalization; Humans; Intensive Care Units; Male; Middle Aged; Patient Discharge; Propensity Score; Risk Factors; Ticagrelor; Treatment Outcome

Topics: Aged; Coronary Artery Disease; Diabetes Mellitus, Type 2; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Ticagrelor; Treatment Outcome

BACKGROUND The purpose of this study was to investigate factors influencing bleeding in patients with acute coronary syndrome (ACS) who are on aspirin and ticagrelor as dual antiplatelet therapy. MATERIAL AND METHODS This retrospective case-control study included 50 patients with ACS (25 with reported bleeding events and 25 without) on aspirin and ticagrelor. Adenosine diphosphate (ADP)- and arachidonic acid (ACA)-induced platelet aggregation rates were measured using light transmission aggregometry. Single-nucleotide polymorphisms (SNPs) in PEAR1, GP1BA, and GSTP1 were genotyped. RESULTS ACA-induced platelet aggregation rates were obviously lower in patients with bleeding events than in those without (13.28±8.46% vs. 24.93±9.89%, P<0.001). No significant differences in ADP-induced platelet aggregation rates were observed between the 2 groups (16.17±9.74% vs. 16.88±12.69%, P>0.05). Among those with bleeding events and among controls, 70% and 80% had an ACA-induced platelet aggregation rate of 0-18% and 18-50%, respectively. Mutation rates of rs6065 in GP1BA and rs1695, rs4891, and rs8191439 in GSTP1 also differed significantly between the 2 groups. CONCLUSIONS Lower ACA-induced platelet aggregation rates are associated with increased risk of bleeding in patients with ACS who are on aspirin and ticagrelor. An ACA-induced platelet aggregation rate of 18% may be considered the cutoff point for identifying high risk of aspirin-associated bleeding events in patients with ACS. SNP genotyping may also help predict the risk of bleeding in patients with ACS.

Topics: Acute Coronary Syndrome; Adenosine Diphosphate; Aged; Arachidonic Acid; Aspirin; Case-Control Studies; Dual Anti-Platelet Therapy; Female; Genotype; Glutathione S-Transferase pi; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIb-IX Complex; Polymorphism, Single Nucleotide; Receptors, Cell Surface; Retrospective Studies; Ticagrelor

Dabigatran etexilate (DABE) is a direct oral anticoagulant (DOAC) and may be combined with ticagrelor, a P2Y

Topics: Anticoagulants; China; Dabigatran; Drug Interactions; Hemorrhage; Humans; Models, Theoretical; Risk Factors; Ticagrelor

Prolonged dual antiplatelet therapy after 12 months in patients with previous myocardial infarction (MI) is attractive to reduce long-term ischemic complications. In the PEGASUS-TIMI 54, the use of low-dose ticagrelor (60 mg b.i.d.) plus aspirin after 12 months from MI reduced the risk of ischemic events, at the price of limited increase on bleeding complications. However, data on the use of low-dose ticagrelor in real-world practice lack. We aim at providing data on prescription/eligibility criteria and outcomes in patients receiving low-dose ticagrelor in the real-world setting. We enrolled consecutive patients eligible for ticagrelor 60 mg according to Italian national regulation in 3 high-volume centers and collected 1-year outcomes. The primary objective of the study is to generate real-world data about clinical characteristics, eligibility criteria, major adverse cardiovascular events, bleeding, and adverse event in patients receiving low-dose ticagrelor from our cohort. One hundred eighty-one patients were consecutively enrolled with a median follow-up of 18 months. The most used and the least used prescription criteria were multivessel coronary disease (72.4%) and chronic kidney disease (15.5%), respectively. At 1-year follow-up, the rate of major adverse cardiovascular events was 4.97%; of these, 3.86% of patients had a MI, and 1.1% had a stroke/transient ischemic attack, whereas no major bleeding occurred. In conclusion, in a real-world study, including patients with previous MI, low-dose ticagrelor for prolonged dual antiplatelet therapy showed to be effective and safe, with no major bleeding occurring at follow-up.

Topics: Aged; Drug Administration Schedule; Dual Anti-Platelet Therapy; Female; Hemorrhage; Humans; Italy; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Prospective Studies; Recurrence; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Coronary endarterectomy (CE) combined with coronary artery bypass grafting (CABG) can be the only option for complete revascularization in some patients with diffuse coronary artery disease. Unfortunately, CE can cause the lack of endothelium, resulting in increased risk of thrombotic events. Therefore, antithrombotic therapy is very important after surgery. However, there's no consistent protocol exists till now. The aim of this study was to compare the effectiveness and safety of dual antiplatelet therapies (DAPT) including aspirin plus clopidogrel (AC) or ticagrelor (AT) after CE + CABG.. A total of 137 continuous patients (mean age 60.0 ± 9.0 years) underwent CE + CABG from January 2016 to July 2018 in our center, and patients who received dual antiplatelet therapy (DAPT) after surgery (n = 121) were included in this study. All of the patients received aspirin 100 mg daily therapy after surgery, and 67 of the patients received extra clopidogrel 75 mg (AC) daily therapy, whereas 54 received extra ticagrelor 90 mg (AT) twice daily. All patients continued aspirin monotherapy after 1 year. Occurrence of ischemic events and bleeding events between two groups were compared. Kaplan-Meier survival was used to compare freedom from major adverse cardiovascular and cerebrovascular events (MACCE) between two groups, and log-rank test was used to confirm statistical difference.. Follow-up was completed by 99.2%, and median follow-up time was 30.0(22.5, 35.2) months. No operative death was observed, while perioperative myocardial infarction was observed in 2(1.7%) patients (AC 1.5% vs. AT 1.9%, p = ns). One patient in AC group suffered from cardiac tamponade. During the follow-up period, no death was observed. Ischemic events including nonfatal myocardial infarction, repeat revascularization and ischemic stroke were observed in 6(5.0%) patients (AC 4.5% vs. AT 5.6%, p = ns). Overt bleeding had occurred in 3(2.5%) patients (AC 3.0% vs. AT 1.9%, p = ns). Kaplan-Meier analysis indicated that MACCE-free survival of the two groups at 3 years was 97.0% in the AC group versus 94.1% in the AT group (p = ns).. In patients undergoing CE + CABG, DAPT therapy can be effective and safe with comparable results between AC and AT therapy in terms of ischemic and bleeding events. Further studies are needed.

Topics: Aged; Aspirin; Clopidogrel; Cohort Studies; Coronary Artery Bypass; Coronary Artery Disease; Dual Anti-Platelet Therapy; Endarterectomy; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

Although ticagrelor has been well-known to improve clinical outcomes in patients undergoing percutaneous coronary intervention (PCI), and its effectiveness and safety have not been well evaluated in Chinese patients. This study aimed to evaluate the effectiveness and safety of ticagrelor in Chinese patients. In order to find potential effect modifiers on the drug effects, a decision tree method was performed to detect interactions between treatment and patient characteristics in an automatic and systematic manner.. This retrospective study included acute coronary syndrome (ACS) patients who underwent PCI and received either ticagrelor (N = 250) or clopidogrel (N = 291) while hospitalized between August 2014 and August 2015. After propensity score matching, Kaplan-Meier analysis was used to study the event-free survival against major adverse cardiovascular events (MACE, primary efficacy outcome, defined as the composite of cardiac death, non-fatal myocardial infarction [MI], stroke, restenosis and target vessel revascularization [TVR]), re-hospitalization, the need for urgent re-PCI (secondary efficacy outcome) and bleeding events (safety outcome) within 12 months of the PCI date. To search for effect modifiers of the two antiplatelet therapies, a machine-learning decision tree algorithm was conducted to predict re-hospitalization status.. After propensity score matching (N = 442), ticagrelor and clopidogrel had no significant difference in MACE, re-hospitalization and bleeding. The decision tree analysis showed that the number of diseased vessels modulated the effect of ticagrelor and clopidogrel on re-hospitalization rates. In single-vessel disease (SVD) patients, ticagrelor was associated with lower hazards than clopidogrel for all efficacy outcomes: MACE (HR = 0.190, 95% CI: 0.042-0.866), re-hospitalization (HR = 0.296, 95% CI: 0.108-0.808), urgent re-PCI (HR = 0.249, 95% CI: 0.069-0.895), bleeding (HR = 1.006, 95% CI: 0.063-16.129). However, in multi-vessel disease (MVD) patients, the two treatments did not show significant difference.. In the general patient population, there was no significant difference between ticagrelor and clopidogrel on the hazard of MACE. However, ticagrelor achieved a better effectiveness than clopidogrel in patients with SVD. This pilot study provides scientific basis to call for a large-scale prospective study in this population.

Topics: Acute Coronary Syndrome; Aged; Algorithms; Asian People; Clopidogrel; Data Mining; Decision Trees; Female; Hemorrhage; Hospitalization; Humans; Machine Learning; Male; Middle Aged; Percutaneous Coronary Intervention; Pilot Projects; Platelet Aggregation Inhibitors; Retrospective Studies; Ticagrelor

Aim      To compare hemorrhagic safety of ticagrelor and clopidogrel in patients with ST-segment elevation acute coronary syndrome (STEACS) after thrombolytic therapy (TLT).Material and methods  This nonrandomized study included 183 patients followed up for 30 days. Hemorrhagic safety was compared in a group of patients with STEACS (n=71) after a thrombolytic treatment with alteplase and early ticagrelor treatment (180 mg followed by switching to 90 mg twice daily) and in a group of patients (n=112) with STEACS receiving TLT with alteplase and clopidogrel (loading dose, 600 mg followed by switching to 75 mg daily). Primary endpoint was hemorrhage associated with TLT; patients were followed up for 30 days.Results During the follow-up period, TLT-associated hemorrhages were observed in 11.3% of patients in the ticagrelor treatment group and in 10.7% of patients in the clopidogrel treatment group (p=0.9; odds ratio, 1.06 at 95 % confidence interval, from 0.41 to 2.73). Intracranial hemorrhages and fatal hemorrhages were absent in both groups.Conclusion      There were no significant differences in hemorrhagic safety between patients with STEACS after the TLT treatment with alteplase and early treatment with ticagrelor or clopidogrel.

Topics: Acute Coronary Syndrome; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Thrombolytic Therapy; Ticagrelor; Treatment Outcome

Time-to-first-event analysis considers only the first event irrespective of its severity. There are several methods to assess trial outcomes beyond time-to-first-event analysis, such as analyzing total events and ranking outcomes. In the GLOBAL LEADERS study, time-to-first-event analysis did not show superiority of ticagrelor monotherapy following one-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention to conventional 12-month DAPT followed by aspirin monotherapy in the reduction of the primary composite end point of all-cause mortality or new Q-wave myocardial infarction. This study sought to explore various analytical approaches in assessing total ischemic and bleeding events after percutaneous coronary intervention in the GLOBAL LEADERS study.. Statistical analyses considering repeated events or event severity showed that ticagrelor monotherapy consistently reduced ischemic and bleeding events by 5% to 8%, compared with conventional 1-year DAPT. Applying multiple statistical methods could emphasize the multiple facets of a trial and result in accurate and more appropriate analyses. Considering the recurrence of ischemic and bleeding events, ticagrelor monotherapy appeared to be beneficial after percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01813435.

Topics: Aspirin; Data Interpretation, Statistical; Dual Anti-Platelet Therapy; Endpoint Determination; Equivalence Trials as Topic; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Research Design; Risk Assessment; Risk Factors; Stroke; Ticagrelor; Time Factors; Treatment Outcome

Baldetti L, Melillo F, Moroni F, et al.

Topics: Acute Coronary Syndrome; Clopidogrel; Hemorrhage; Humans; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor

Gimbel M, Qaderdan K, Willemsen L, et al.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Hemorrhage; Humans; Patients; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor

Patients with both diabetes mellitus (DM) and chronic kidney disease (CKD) are a subpopulation characterized by ultrahigh ischemic and bleeding risk after percutaneous coronary intervention. There are limited data on the impact of ticagrelor monotherapy among these patients.. In this post hoc analysis of the GLOBAL-LEADERS trial, the treatment effects of the experimental (one-month dual-antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus the reference regimen (12-month DAPT followed by 12-month aspirin alone) were analyzed according to DM/CKD status. The primary endpoint was a composite endpoint of all-cause death or new Q-wave myocardial infarction at 2-years. The patient-oriented composite endpoint (POCE) was defined as the composite of all-cause death, any stroke, site-reported MI and any revascularization, whereas net adverse clinical events (NACE) combined POCE with BARC type 3 or 5 bleeding events.. At 2 years, the DM + /CKD + patients had significantly higher incidences of the primary endpoint (9.5% versus 3.1%, adjusted HR 2.16; 95% CI [1.66-2.80], p < 0.001), BARC type 3 or 5 bleeding events, stroke, site-reported myocardial infraction, all revascularization, POCE, and NACE, compared with the DM-/CKD- patients. Among the DM + /CKD + patients, after adjustment, there were no significant differences in the primary endpoints between the experimental and reference regimen; however, the experimental regimen was associated with lower rates of POCE (20.6% versus 25.9%, HR 0.74; 95% CI [0.55-0.99], p = 0.043, p. Among patients with both DM and CKD, ticagrelor monotherapy was not associated with lower rates of all-cause death or new Q-wave, or major bleeding complications; however, it was associated with lower rates of POCE and NACE. These findings should be interpreted as hypothesis-generating.. ClinicalTrials.gov (NCT01813435).

Topics: Aged; Aged, 80 and over; Asia; Australia; Brazil; Canada; Coronary Artery Disease; Diabetes Mellitus; Drug-Eluting Stents; Europe; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prevalence; Randomized Controlled Trials as Topic; Recurrence; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Secondary Prevention; Stroke; Ticagrelor; Time Factors; Treatment Outcome

Current guidelines recommend ticagrelor as the preferred P2Y12 platelet inhibitor for patients with acute coronary syndrome (ACS), primarily based on a single large randomized clinical trial. The benefits and risks associated with ticagrelor vs clopidogrel in routine practice merits attention.. To determine the association of ticagrelor vs clopidogrel with ischemic and hemorrhagic events in patients undergoing percutaneous coronary intervention (PCI) for ACS in clinical practice.. A retrospective cohort study of patients with ACS who underwent PCI and received ticagrelor or clopidogrel was conducted using 2 United States electronic health record-based databases and 1 nationwide South Korean database from November 2011 to March 2019. Patients were matched using a large-scale propensity score algorithm, and the date of final follow-up was March 2019.. Ticagrelor vs clopidogrel.. The primary end point was net adverse clinical events (NACE) at 12 months, composed of ischemic events (recurrent myocardial infarction, revascularization, or ischemic stroke) and hemorrhagic events (hemorrhagic stroke or gastrointestinal bleeding). Secondary outcomes included NACE or mortality, all-cause mortality, ischemic events, hemorrhagic events, individual components of the primary outcome, and dyspnea at 12 months. The database-level hazard ratios (HRs) were pooled to calculate summary HRs by random-effects meta-analysis.. After propensity score matching among 31 290 propensity-matched pairs (median age group, 60-64 years; 29.3% women), 95.5% of patients took aspirin together with ticagrelor or clopidogrel. The 1-year risk of NACE was not significantly different between ticagrelor and clopidogrel (15.1% [3484/23 116 person-years] vs 14.6% [3290/22 587 person-years]; summary HR, 1.05 [95% CI, 1.00-1.10]; P = .06). There was also no significant difference in the risk of all-cause mortality (2.0% for ticagrelor vs 2.1% for clopidogrel; summary HR, 0.97 [95% CI, 0.81-1.16]; P = .74) or ischemic events (13.5% for ticagrelor vs 13.4% for clopidogrel; summary HR, 1.03 [95% CI, 0.98-1.08]; P = .32). The risks of hemorrhagic events (2.1% for ticagrelor vs 1.6% for clopidogrel; summary HR, 1.35 [95% CI, 1.13-1.61]; P = .001) and dyspnea (27.3% for ticagrelor vs 22.6% for clopidogrel; summary HR, 1.21 [95% CI, 1.17-1.26]; P < .001) were significantly higher in the ticagrelor group.. Among patients with ACS who underwent PCI in routine clinical practice, ticagrelor, compared with clopidogrel, was not associated with significant difference in the risk of NACE at 12 months. Because the possibility of unmeasured confounders cannot be excluded, further research is needed to determine whether ticagrelor is more effective than clopidogrel in this setting.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Algorithms; Aspirin; Case-Control Studies; Cause of Death; Clopidogrel; Databases, Factual; Dyspnea; Female; Hemorrhage; Humans; Ischemia; Male; Middle Aged; Myocardial Infarction; Network Meta-Analysis; Percutaneous Coronary Intervention; Propensity Score; Purinergic P2Y Receptor Antagonists; Recurrence; Republic of Korea; Retrospective Studies; Stroke; Ticagrelor; United States

Although premature discontinuation of dual antiplatelet therapy (DAPT) is associated with an increased risk of ischemic complications, patients may present with an urgent need for surgery that would require interruption of DAPT. Antiplatelet bridge therapy using cangrelor, an intravenous P2Y

Topics: Acute Coronary Syndrome; Adenosine Monophosphate; Aged; Aspirin; Biopsy; Bronchoscopy; Clopidogrel; Drug Therapy, Combination; Drug-Eluting Stents; Dual Anti-Platelet Therapy; Female; Hemorrhage; Humans; Perioperative Care; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor

The benefits of short versus long-term dual antiplatelet therapy (DAPT) based on the third generation P2Y12 antagonists prasugrel or ticagrelor, in patients with acute coronary syndromes treated with percutaneous coronary intervention remain to be clearly defined due to current evidences limited to patients treated with clopidogrel.. All acute coronary syndrome patients from the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) undergoing percutaneous coronary intervention and treated with aspirin, prasugrel or ticagrelor were stratified according to DAPT duration, that is, shorter than 12 months (D1 group), 12 months (D2 group) and longer than 12 months (D3 group). The three groups were compared before and after propensity score matching. Net adverse clinical events (NACEs), defined as a combination of major adverse cardiac events (MACEs) and major bleedings (including therefore all cause death, myocardial infarction and Bleeding Academic Research Consortium (BARC) 3-5 bleeding), were the primary end points, MACEs (a composite of all cause death and myocardial infarction) the secondary one. Single components of NACEs were co-secondary end points, along with BARC 2-5 bleeding, cardiovascular death and stent thrombosis.. A total of 4424 patients from the RENAMI registry with available data on DAPT duration were included in the model. After propensity score matching, 628 patients from each group were selected. After 20 months of follow up, DAPT for 12 months and DAPT for longer than 12 months significantly reduced the risk of NACE (D1 11.6%. In unselected real world acute coronary syndrome patients treated with percutaneous coronary intervention, DAPT with prasugrel or ticagrelor prolonged beyond 12 months markedly reduces fatal and non-fatal ischaemic events, offsetting the increased risk deriving from the higher bleeding risk. On the contrary, patients >75 years old and female ones showed a less favourable risk-benefit ratio for longer DAPT due to excess of bleedings.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Drug Administration Schedule; Dual Anti-Platelet Therapy; Europe; Female; Hemorrhage; Humans; Male; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Recurrence; Registries; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Stents; Ticagrelor; Time Factors; Treatment Outcome

In patients with acute coronary syndrome (ACS), treatment using ticagrelor demonstrated significant ischemic benefits over clopidogrel; however, it was associated with increased bleeding complications leading to frequent de-escalation to clopidogrel. The objective of the present study was to investigate the efficacy and safety of de-escalation in early and late phase after percutaneous coronary intervention (PCI). We performed a retrospective study of 4678 ACS patients from March 2016 to April 2017 who initially received ticagrelor then de-escalated to clopidogrel and categorized them into Group 1: early phase (1-30 days) and Group 2: late phase (>30 days-1 year) switching groups. The primary efficacy endpoints included cardiovascular death, definite/probable stent thrombosis, myocardial infarction, unplanned revascularization, and stroke. The safety endpoint was Bleeding Academic Research Consortium classification 3 or 5 bleeding events within 1 year after PCI. The incidence of switching occurred in 1019 patients; 380 (37.3%) in Group 1 (median 14 days, interquartile range 4-30 days) versus 639 (62.7%) in Group 2 (median 180 days, interquartile range 90-270 days). The ischemic endpoints occurred in 53 (13.9%) patients in Group 1 versus 35 (5.4%) in Group 2 (HR 1.93,95%CI 1.22-3.08, p < .0001). There were no significant differences of major bleeding events (HR 0.91; 95%CI, 0.58-1.43, p = .90) seen between the groups. The main cause for switching between the two groups was due to BARC 1 or 2 bleeding types. Early de-escalation from ticagrelor to clopidogrel during the initial 30 days after ACS was associated with higher risk of ischemic events when compared with switching beyond 30 days.

Topics: Acute Coronary Syndrome; China; Clopidogrel; Drug Substitution; Electrocardiography; Follow-Up Studies; Hemorrhage; Humans; Kaplan-Meier Estimate; Magnetic Resonance Angiography; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Retrospective Studies; Ticagrelor; Tomography, X-Ray Computed; Treatment Outcome

Topics: Antifibrinolytic Agents; Clopidogrel; Coronary Artery Bypass; Hemorrhage; Humans; Ticagrelor

Many patients with acute coronary syndrome may experience recurrent myocardial infarction although they are receiving optional therapy, but they are still associated with poor clincial outcomes. The goal of this study was to assess different antiplatelet strategies in these patients.. This retrospective trial compared ticagrelor (180-mg loading dose, 90-mg BID maintenance dose) and clopidogrel (300- to 600-mg loading dose, 150-mg daily maintenance dose) for the prevention of cardiovascular events in 1083 patients with acute coronary syndrome and recurrent myocardial infarction admitted to the hospital undergoing percutaneous coronary intervention.. At the 24-month follow-up, a major adverse cardiovascular and cerebrovascular event (MACCE) occurred in 10.5% of patients receiving ticagrelor compared with 13.2% in the clopidogrel group (P = 0.023). Meanwhile, ticagrelor caused a higher rate of minor bleeding (18.1% vs 15.3%; P = 0.008). A survival analysis showed that ticagrelor decreased the incidence of MACCE (log-rank test, P < 0.001) and all-cause death (log-rank test, P = 0.001). The advantage of ticagrelor was also presented according to analysis of Seattle Angina Questionnaire scores.. In patients with recurrent myocardial infarction, the ticagrelor antiplatelet strategy significantly reduced the MACCE rate without increasing the risk of major bleeding, although patients did have a higher risk of minor bleeding.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Retrospective Studies; Survivors; Ticagrelor; Treatment Outcome

Topics: Clinical Trials, Phase IV as Topic; Coronary Artery Disease; Coronary Thrombosis; Hemorrhage; Humans; Medication Adherence; Multicenter Studies as Topic; Patient Safety; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Risk Factors; Ticagrelor; Treatment Outcome

International guidelines recommend ticagrelor over clopidogrel as preferred antiplatelet agent in patients following coronary stenting. However, no large real-life evidence is available in East Asians in general, and Chinese in particular, with regard to associated clinical outcomes. The present study aimed to assess the early and delayed outcomes after ticagrelor versus clopidogrel in post stenting Chinese patients.. We conducted the pre-specified interim analysis of Comparison Of Efficacy and Safety Between TIcagrelor and Clopidogrel In Chinese (COSTIC), the ongoing prospective, observational, single-center trial. Primary outcomes include first occurrence of myocardial infarction, stroke, vascular death and Bleeding Academic Research Consortium (BARC) scale bleeding event. Propensity score matching (PSM) was carried out to adjust for differences in baseline characteristics between treatment arms.. In total, 4,465 patients were enrolled. After PSM, the patients prescribed with ticagrelor had a lower incidence of primary efficacy endpoint relative to those with clopidogrel (0.6% vs. 1.4%, HR = 0.44, 95%CI: 0.22-0.89, p = 0.019) at 1 month, but similar at 7 days, 6 months and 12 months. Further analysis indicated that the difference only exists in the subgroup of acute myocardial infarction (AMI) patients. With regard to safety, ticagrelor consistently increased the risk of BARC type 2 bleeding compared to clopidogrel at 1 month, 6 months and 12 months.. These preliminary data indicate that ticagrelor is superior to clopidogrel with regard to major vascular thrombotic outcomes at 1 month, especially in the AMI population, but both groups are similar at 7 days, 6 months and 12 months. Ticagrelor consistently caused significantly more BARC type 2 bleeding.

Topics: Acute Coronary Syndrome; Aged; Asian People; China; Clopidogrel; Coronary Thrombosis; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Registries; Risk Assessment; Risk Factors; Stents; Ticagrelor; Time Factors; Treatment Outcome

Impact of sex-related differences in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention and treated with new P2Y12 inhibitors is not adequately characterised. We aimed to analyse gender-based differences in dual antiplatelet therapy, and adverse cardiovascular events and bleeding.. Prospective-observational study of the consecutive ACS patients treated with stent from July 2016 to January 2016, with a follow-up of 1 year.. We examined 283 patients, 75 (26.5%) women and 208 (73.5%) men. Women were older than men (71 ± 13 vs. 66,5 ± 13 years). There were 44% of women and 52% of men presenting with ST-elevation ACS (p = 0.21). Women had a higher bleeding risk (CRUSADE), without differences in the ischaemic risk (GRACE and TIMI). More women were treated with drug-eluting stent (88.9 vs. 75.5%, p = 0.04). There was a lower rate of ticagrelor prescription in women (42.6 vs. 50.9%, p = 0.29), in favour of clopidogrel. No differences were observed in prasugrel prescription. No significant differences were observed after a year of follow up, but women had a tendency towards lower mortality (1.4 vs. 6.7%, p = 0.19) and higher bleeding rates (23.3 vs. 17.4%, p = 0.27).. In our study of patients presenting with ACS treated with stent, clopidogrel was preferred in women, whereas ticagrelor was the most frequent prescription in men. No significant differences were noted in clinical outcomes, but women experienced a tendency towards less mortality and more bleeding events.. El interés sobre la influencia del sexo en pacientes con síndrome coronario agudo (SCA) tratados con stent y nuevos antiagregantes inhibidores de P2Y12 en la práctica clínica es creciente. Se analizan las diferencias en función del sexo en el tratamiento con doble antiagregación plaquetaria (DAPT) y los eventos adversos isquémicos y hemorrágicos.. Estudio prospectivo de pacientes consecutivos con diagnóstico de SCA tratados con stent coronario desde julio de 2015 hasta enero de 2016.. De un total de 283 pacientes incluidos, 75 (26.5%) correspondió a mujeres y 208 (73.5%) a hombres. La edad media fue de 71 ± 13 y 66.5 ± 13 años, respectivamente. Un 44% de mujeres se presentó como SCA con elevación del segmento ST contra un 52.4 de los hombres, p = 0.21. Las mujeres mostraron un mayor riesgo de sangrado (CRUSADE), sin diferencias en el riesgo isquémico (GRACE y TIMI). Se usaron stents farmacoactivos con más frecuencia en mujeres (88.9 vs. 75.5%, p = 0.04). Se observó una tendencia de menor prescripción del ticagrelor en mujeres (42.6 vs. 50.9%, p = 0.29) en favor de un mayor uso del clopidogrel. No se identificaron diferencias en cuanto a la prescripción del prasugrel. Las mujeres presentaron al año una menor mortalidad (1.4 vs. 6.7%, p = 0.19), aunque mayor sangrado (23.3 vs. 17.4%, p = 0.27).. En este estudio de pacientes consecutivos con SCA tratados con stent se registró una mayor prescripción de clopidogrel en las mujeres que en los hombres. Las mujeres presentaron una menor incidencia anual de mortalidad, pero mayor sangrado en comparación con los hombres, no significativo.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Clopidogrel; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Practice Patterns, Physicians'; Prognosis; Prospective Studies; Purinergic P2Y Receptor Antagonists; Sex Factors; Stents; Ticagrelor; Ticlopidine

The PARIS score allows combined stratification of ischemic and hemorrhagic risk in patients with ischemic heart disease treated with coronary stenting and dual antiplatelet therapy (DAPT). Its usefulness in patients with acute coronary syndrome (ACS) treated with ticagrelor or prasugrel is unknown. We investigated this issue in an international registry.. Retrospective multicenter study with voluntary participation of 11 centers in 6 European countries. We studied 4310 patients with ACS discharged with DAPT with ticagrelor or prasugrel. Ischemic events were defined as stent thrombosis or spontaneous myocardial infarction, and hemorrhagic events as BARC (Bleeding Academic Research Consortium) type 3 or 5 bleeding. Discrimination and calibration were calculated for both PARIS scores (PARIS. During a period of 17.2 ± 8.3 months, there were 80 ischemic events (1.9% per year) and 66 bleeding events (1.6% per year). PARIS. In patients with ACS treated with DAPT with ticagrelor or prasugrel, the PARIS model helps to properly evaluate the ischemic-hemorrhagic risk.

Topics: Acute Coronary Syndrome; Aged; Dose-Response Relationship, Drug; Drug Therapy, Combination; Europe; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Ischemia; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Registries; Retrospective Studies; Risk Assessment; Ticagrelor; Treatment Outcome

To compare the prescription rates, safety, and efficacy of contemporary P2Y. From 9684 ACS patients who underwent PCI in a nationwide, real-world registry, we compared prescription rates, bleeding, and major adverse cardiac events (MACEs: cardiac death, nonfatal myocardial infarction, or stroke) according to ticagrelor, prasugrel, or clopidogrel use.. The prescription rates of ticagrelor, prasugrel, and clopidogrel were 15.2%, 11.7%, and 73.0%, respectively. In-hospital bleeding occurred in 565 (5.8%) patients, with 108 (7.3%), 80 (7.9%), and 377 (5.3%) patients using ticagrelor, prasugrel, and clopidogrel, respectively, with significantly higher incidence in ticagrelor (p = 0.008) and prasugrel (p = 0.026) users than in clopidogrel users. Ticagrelor and prasugrel were not different in terms of in-hospital bleeding (p = 0.159). MACEs occurred in 804 patients (8.3%), with 82 (5.6%), 69 (6.1%), and 653 (9.2%) patients in ticagrelor, prasugrel, and clopidogrel, respectively (median follow-up, 468 days). Ticagrelor (p = 0.001) and prasugrel (p = 0.001) were associated with fewer MACEs than clopidogrel; the difference between ticagrelor and prasugrel for fewer MACEs was nonsignificant (p = 0.235).. In real-world ACS patients following PCI, ticagrelor and prasugrel were not prescribed at higher rates than clopidogrel, but were found to improve clinical outcomes, albeit they induced bleeding more frequently. No differences were observed in bleeding and outcomes in ticagrelor versus prasugrel.

Topics: Acute Coronary Syndrome; Cause of Death; Clopidogrel; Drug Prescriptions; Follow-Up Studies; Hemorrhage; Humans; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Prognosis; Prospective Studies; Purinergic P2Y Receptor Antagonists; Registries; Republic of Korea; Survival Rate; Ticagrelor

The safety and efficacy of prasugrel and ticagrelor in patients with diabetes mellitus presenting with acute coronary syndrome and treated with percutaneous coronary intervention remain to be assessed.. All diabetes patients admitted for acute coronary syndrome and enrolled in the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) were compared before and after propensity score matching. Net adverse cardiovascular events (composite of death, stroke, myocardial infarction and BARC 3-5 bleedings) and major adverse cardiovascular events (composite of death, stroke and myocardial infarction) were the co-primary endpoints. Single components of primary endpoints were secondary endpoints.. Among 4424 patients enrolled in RENAMI, 462 and 862 diabetes patients treated with prasugrel and ticagrelor, respectively, were considered. After propensity score matching, 386 patients from each group were selected. At 19±5 months, major adverse cardiovascular events and net adverse cardiovascular events were similar in the prasugrel and ticagrelor groups (5.4% vs. 3.4%,. Diabetes patients admitted for acute coronary syndrome seem to benefit equally in terms of major adverse cardiovascular events from ticagrelor or prasugrel use. Ticagrelor was associated with a significant reduction in all-cause death and bleedings, without differences in recurrent ischaemic events, which should be confirmed in dedicated randomised controlled trials.

Topics: Acute Coronary Syndrome; Aged; Case-Control Studies; Coronary Angiography; Diabetes Complications; Diabetes Mellitus; Hemorrhage; Hospitalization; Humans; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Propensity Score; Recurrence; Registries; Safety; Stents; Thrombosis; Ticagrelor; Treatment Outcome

The French Working Group on Perioperative Haemostasis (GIHP) and the French Study Group on Haemostasis and Thrombosis (GFHT) in collaboration with the French Society of Anaesthesia and Intensive Care Medicine (SFAR) drafted up-to-date proposals on the management of antiplatelet therapy for non-elective invasive procedures or bleeding complications. The proposals were discussed and validated by a vote; all proposals could be assigned with a high strength. Emergency management of oral antiplatelet agents (APA) requires knowledge on their pharmacokinetic/pharmacodynamics parameters, evaluation of the degree of the alteration of haemostatic competence and the associated bleeding risk. Platelet function testing may be considered. When APA-induced bleeding risk may worsen the prognosis, measures should be taken to neutralise antiplatelet therapy by considering not only the efficacy of available means (which can be limited for prasugrel and even more for ticagrelor) but also the risks that these means expose the patient to. The measures include platelet transfusion at the appropriate dose and haemostatic agents (tranexamic acid; rFVIIa for ticagrelor). When possible, postponing non-elective invasive procedures at least for a few hours until the elimination of the active compound (which could compromise the effect of transfused platelets) or if possible a few days (reduction of the effect of APA) should be considered.

Topics: Anesthesia; Critical Care; France; Hemorrhage; Hemostasis; Hemostasis, Surgical; Hemostatics; Humans; Platelet Aggregation Inhibitors; Platelet Function Tests; Platelet Transfusion; Prasugrel Hydrochloride; Prognosis; Societies, Medical; Ticagrelor

European Guidelines on Myocardial Revascularization recommend clopidogrel loading dose added to acetylsalicylic acid in elective percutaneous coronary interventions (PCIs). However, there is few evidence supporting this recommendation and other P2Y12 inhibitors have not been tested in these patients.. To evaluate the effectiveness and safety of different loading doses of clopidogrel and ticagrelor in patients without double antiplatelet therapy and stable coronary artery disease (SCAD) undergoing elective PCI.. Retrospective study of 147 consecutive patients with SCAD undergoing elective PCI. Loading P2Y12 inhibitor doses evaluated were: clopidogrel 600 mg, clopidogrel 300 mg, clopidogrel 150 mg, and ticagrelor 180 mg. We analyzed the occurrence of major adverse cardiovascular events and periprocedural myocardial infarction.. One hundred twenty-five patients were treated with clopidogrel (16 with clopidogrel 150 mg, 7 with clopidogrel 300 mg, and 93 with clopidogrel 600 mg) and 21 with ticagrelor 180 mg at the catheterization laboratory. The ticagrelor group had a significantly lower postprocedural peak of troponin-I (0.7 ± 3.4 vs. 0.3 ± 0.7 ng/mL; P = 0.02). There were no differences between groups in terms of major bleeding and hemoglobin drop after PCI (0.6 ± 0.8 vs. 4 ± 0.6; P = 0.8). The median of follow-up was 17 months (interquartile range 9-32.7). At the end of follow-up, major adverse cardiovascular event rate was not different between groups.. In patients without dual antiplatelet therapy undergoing elective PCI, the use of ticagrelor showed lower postprocedural myocardial injury without more bleeding complications.

Topics: Aged; Aged, 80 and over; Clopidogrel; Coronary Artery Disease; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Potent P2Y12 blockers are preferred in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI). However, the risk of bleeding remains a major concern. We assessed the association of potent P2Y12 blockers with ischemic and bleeding outcomes in patients with NSTEMI.. From the Korea Acute Myocardial Infarction Registry-National Institute of Health database, 4927 patients with NSTEMI receiving drug-eluting stents (DES) were divided into potent P2Y12 blocker (ticagrelor or prasugrel, n=901) and clopidogrel (n=3180) groups. Propensity-matched 12-month ischemic and bleeding events were compared. Patients who received anticoagulants or who discontinued P2Y12 blockers or switched between potent P2Y12 blockers and clopidogrel were excluded.. In the overall population, patients at higher ischemic and bleeding risks more often received clopidogrel. After propensity matching (n=901 in each group), 12-month rates of major adverse cardiac and cerebrovascular events were lower (7.3% vs. 10.1%, p=0.038), but Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding rates were higher (5.9% vs. 2.2%, p<0.001) with potent P2Y12 blockers. Twelve-month rates of death from any cause, MI, stroke, or TIMI major bleeding were not different. On multivariate analysis, 12-month risk of TIMI major or minor bleeding was higher with B2 or C lesion, potent P2Y12 blocker use, body weight <60kg, and lower with time to PCI <12h and radial artery access.. In patients with NSTEMI receiving DES, potent P2Y12 blockers were associated with reduced ischemic but increased bleeding risk with similar net clinical benefits.

Topics: Aged; Clopidogrel; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Propensity Score; Purinergic P2Y Receptor Antagonists; Registries; Republic of Korea; Stroke; Ticagrelor

Balancing ischemic and bleeding risk is an evolving framework.. Our objectives were to simulate changes in risks for adverse events and event-driven costs with use of ticagrelor or prasugrel versus clopidogrel according to varying levels of ischemic and bleeding risk. Using the validated PARIS risk functions, we estimated 1-year ischemic (myocardial infarction or stent thrombosis) and bleeding (Bleeding Academic Research Consortium types 3 or 5) event rates among PARIS study participants who underwent percutaneous coronary intervention with drug-eluting stent implantation for an acute coronary syndrome and were discharged with aspirin and clopidogrel (n=1497). Simulated changes in adverse events with ticagrelor or prasugrel were calculated by applying treatment effects from randomized trials for a 1-year time horizon. Event costs were estimated using National Inpatient Sample data. Net costs were calculated between antiplatelet therapy groups according to level of ischemic and bleeding risk. After weighting events for quality-of-life impact, we calculated event rates and costs for risk-tailored treatment versus clopidogrel under multiple drug pricing assumptions. One-year rates (per 1000 person-years) for ischemic events were 12.6, 24.1, and 66.1, respectively, among those at low (n=630), intermediate (n=536), and high (n=331) ischemic risk. Analogous bleeding rates were 11.0, 23.9, and 66.2, respectively, among low (n=728), intermediate (n=634), and high (n=135) bleeding risk patients. Mean per event costs were $22 174 (ischemic) and $12 203 (bleeding). When risks for ischemia matched or exceeded bleeding, simulated utility-weighted event rates favored ticagrelor/prasugrel, whereas clopidogrel reduced utility-weighted events when bleeding exceeded ischemic risk. One-year costs were sensitive to drug pricing assumptions, and risk-tailored treatment with either agent progressed from cost incurring to cost saving with increasing generic market share.. Tailoring antiplatelet therapy intensity to patient risk may improve health utility and could produce cost savings in the first year after percutaneous coronary intervention.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT00998127.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Clinical Decision-Making; Clopidogrel; Coronary Thrombosis; Cost Savings; Cost-Benefit Analysis; Drug Costs; Drug-Eluting Stents; Europe; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Registries; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; United States

Dual antiplatelet therapy is one of the main treatments in acute coronary syndrome (ACS). Switching antiplatelet agents may be necessary in some patients to improve efficacy or safety. The objective of this study was to determine the prevalence, predictors, and implications of clinical switching in patients during hospital admission and 1-year follow-up at discharge.. Observational, prospective, multicenter registry study in patients discharged following an admission for ACS and followed up for 1 year. We analyzed ischemic and bleeding events as well as treatment changes.. We recruited 1717 patients; in-hospital switching occurred in 425 (24.8%): 15.1% to clopidogrel and 84.9% to newer antiplatelet drugs (prasugrel or ticagrelor). Those switched to newer antiplatelets were younger, with lower scores on the GRACE and CRUSADE scales, admitted more frequently for ST-elevation myocardial infarction and underwent more invasive management and percutaneous revascularization. The clinical cardiologist was responsible for most in-hospital switching to newer antiplatelets (79.6%). The loading dose of the second antiplatelet did not affect incidence of bleeding events. Post-discharge switching was infrequent (2%) and depended mainly on clinical indications; only 30% was related to a new ACS.. In a contemporary registry with ACS, in-hospital switching of antiplatelet drugs was frequent. Those switched to newer antiplatelets were younger and admitted more frequently for ST-elevation myocardial infarction. Post-discharge switching was infrequent.

Topics: Acute Coronary Syndrome; Administration, Oral; Aged; Aged, 80 and over; Clopidogrel; Female; Hemorrhage; Hospitalization; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prevalence; Prognosis; Prospective Studies; Purinergic P2Y Receptor Antagonists; Registries; ST Elevation Myocardial Infarction; Ticagrelor

We aimed to compare the effectiveness of ticagrelor vs. clopidogrel or prasugrel on recurrence of acute coronary syndromes (ACS) in real-life conditions, as requested by regulatory authorities at the time of marketing.. We performed a cohort study in SNDS, the French national healthcare database. All patients with a hospital admission for ACS in 2013 were followed one year. Patients on ticagrelor, clopidogrel or prasugrel were matched 1:1 using age, gender, index ACS type, and high-dimensional propensity scores (hdPS). Outcomes were ACS, stroke, all-cause death, and major bleeding, compared within matched groups using Cox proportional hazards models analysis during treatment.. 54,048 ACS were hospitalized in 2013. At discharge, 19,796 were dispensed clopidogrel, 8242 prasugrel, and 13,916 ticagrelor. Per group, 9224 ticagrelor vs. clopidogrel, 6752 ticagrelor vs. prasugrel, and 4676 prasugrel vs. clopidogrel patients were matched. Compared to clopidogrel, ticagrelor was associated with a lower hazard ratio of death 0.73 [0.59-0.90] and composite criterion (0.88, 95% CI [0.79-0.99] but not ACS 0.92 [0.80-1.06], stroke (0.96 [017-5.53]) or major bleeding (1.02 [0.82-1.26]). Prasugrel was not different from ticagrelor or clopidogrel for any outcome, in matched patients.. Ticagrelor in real-life conditions in matched populations was associated with a lower risk of all-cause death than clopidogrel, and a lower risk of composite outcome, as in the main pivotal clinical trial. Ticagrelor and prasugrel were not different, nor were prasugrel and clopidogrel.

Topics: Acute Coronary Syndrome; Administrative Claims, Healthcare; Aged; Clopidogrel; Comparative Effectiveness Research; Databases, Factual; France; Hemorrhage; Humans; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Recurrence; Risk Factors; Secondary Prevention; Ticagrelor; Time Factors; Treatment Outcome

This study investigated the efficacy and safety of ticagrelor compared with clopidogrel in patients with end-stage renal disease (ESRD) and acute myocardial infarction (AMI).. We retrospectively enrolled patients who had received regular dialysis and had undergone percutaneous coronary intervention (PCI) for AMI at our hospital between January 2013 and December 2016. Outcomes analyzed included cardiovascular death, death from any cause, MI, stroke, and bleeding events.. Patients were allocated to the ticagrelor group (N = 74) or the clopidogrel group (N = 116) according to the treatment they had received. No statistically significant differences were found between the groups in terms of in-hospital primary endpoint (composite of cardiovascular death, MI, and stroke: 12.2% and 15.5% for ticagrelor and clopidogrel, respectively; p = 0.518), secondary endpoint, or any bleeding events (39.2 vs. 34.5%; p = 0.511). No statistically significant differences were found for the 1-year primary endpoint (p = 0.424), secondary endpoint, and any bleeding events (p = 0.663). Risk factors for in-hospital cardiovascular death were shock and cardiopulmonary resuscitation at initial AMI presentation, lack of beta-blocker use, and in-hospital gastrointestinal bleeding. Risk factors for 1-year cardiovascular death were shock at initial AMI presentation and lack of beta-blocker use. Only respiratory failure was a risk factor for in-hospital and 1-year gastrointestinal bleeding.. In patients with ESRD and AMI, ticagrelor resulted in numerically fewer but statistically nonsignificant rates of in-hospital and 1-year cardiovascular events with no significant increase in bleeding events compared with clopidogrel.

Topics: Aged; Clopidogrel; Female; Hemorrhage; Humans; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Stroke; Ticagrelor; Treatment Outcome

Ticagrelor has been widely accepted in clinical practice for treatment of acute myocardial infarction (AMI), however its clinical safety and efficacy have not been revealed sufficiently in Asian populations.. Among a total 20,270 patients (age <75 years) with AMI undergoing percutaneous coronary intervention who received dual antiplatelet therapy for at least 30 days, clinical outcomes at 1 year were assessed from the database of Health Insurance Review and Assessment Service in Korea between 2013 and 2014. Ticagrelor showed a significant effect on reduction of all-cause death [stabilized inverse probability of treatment weighted (sIPTW)-adjusted odds ratio (aOR) 0.57, 95% confidence interval (CI) 0.42-0.77, p<0.001]. Stroke was also reduced by using ticagrelor (sIPTW-aOR 0.58, 95% CI 0.41-0.82, p=0.002). Bleeding risk was not increased by ticagrelor use. There were nearly 30% of patients who switched from ticagrelor to different P2Y12 inhibitors. Switching P2Y12 inhibitors was associated with clinical adverse events including MI, stroke, and bleeding.. Among patients aged younger than 75 years, ticagrelor was associated with lower incidence of all-cause mortality. Stroke risk was also reduced in patients with a prescription for ticagrelor without an increase in bleeding risk.

Topics: Aged; Cause of Death; Clopidogrel; Combined Modality Therapy; Drug Substitution; Female; Hemorrhage; Humans; Incidence; Insurance, Health; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Republic of Korea; Stroke; Ticagrelor; Treatment Outcome

Pretreatment of patients with ST-elevation myocardial infarction (STEMI) with P2Y12 receptor antagonists is supported by guidelines and is a common practice despite the lack of definite evidence for its benefit.. Using data from the Swedish Coronary Angiography and Angioplasty Registry on procedures between 2005 and 2016, we stratified all patients who underwent primary percutaneous coronary intervention due to STEMI in Sweden by whether or not they were pretreated with P2Y12 receptor antagonists. We investigated associations between pretreatment with P2Y12 receptor antagonists and the risk of adverse outcomes using propensity score-adjusted mixed-effects logistic regression, which accounted for clustering of patients within hospitals. The primary endpoint was all-cause death within 30 days. Secondary endpoints were infarct-related artery (IRA) occlusion, 30-day stent thrombosis, in-hospital bleeding, neurological complications, and cardiogenic shock. In total, 44 804 patients were included. They were treated with clopidogrel (N = 26 136, 58.3%), ticagrelor (N = 15 792, 35.3%), or prasugrel (N = 2352, 5.3%); 37 840 (84.5%) were pretreated, and 30 387 (67.8%) had IRA occlusion. At 30 days, there were 2488 (5.6%) deaths and 267 (0.6%) stent thrombosis. Pretreatment was not associated with better survival at 30 days [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.95-1.24; P = 0.313], reduced IRA occlusion (OR 0.98, 95% CI 0.92-1.05; P = 0.608), decreased stent thrombosis (OR 0.99, 95% CI 0.69-1.43; P = 0.932), higher risk of in-hospital bleeding (OR 1.05, 95% CI 0.89-1.26; P = 0.526), or neurological complications (OR 0.72, 95% CI 0.43-1.21; P = 0.210).. Pretreatment of STEMI patients with P2Y12 receptor antagonists was not associated with improved clinical outcomes.

Topics: Aged; Aged, 80 and over; Angioplasty; Clopidogrel; Coronary Angiography; Female; Hemorrhage; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Registries; ST Elevation Myocardial Infarction; Stents; Survival Rate; Sweden; Thrombosis; Ticagrelor

Topics: Clopidogrel; Coronary Artery Bypass; Hemorrhage; Humans; Ticagrelor

Percutaneous treatment of coronary bifurcation lesions can potentially lead to higher risk of ischemic events than the nonbifurcation ones, thus calling for further optimization of dual antiplatelet therapy (DAPT). This study aimed to compare the clinical outcomes from ticagrelor and clopidogrel in bifurcation lesions patients undergoing percutaneous coronary intervention (PCI).. We performed a retrospective cohort study in patients with coronary bifurcation lesions. A total of 553 patients discharged on ticagrelor or clopidogrel combined with aspirin were recruited for 1-year follow-up. The incidences of primary endpoint (major adverse cardiovascular event [MACE]: a composite of cardiac death, myocardial infarction [MI] or stroke), secondary endpoints (the individual component of the primary endpoint or definite/probable stent thrombosis), and major bleeding (Bleeding Academic Research Consortium [BARC]≥3 bleeding events) were evaluated. To minimize the selection bias, a propensity score-matched population analysis was also conducted.. The risks of both primary endpoint (8.15% and 12.01% for the ticagrelor and clopidogrel groups, respectively; adjusted hazards ratio [HR]: 0.488, 95% confidence interval [CI]: 0.277-0.861, P=0.013) and MI (4.44% and 8.48% for the ticagrelor and clopidogrel groups, respectively; adjusted HR: 0.341, 95% CI: 0.162-0.719, P=0.005) were significantly reduced in the ticagrelor group as compared with those of the clopidogrel counterpart, whereas the risk of major bleeding was comparable (2.96% and 2.47% for the ticagrelor and clopidogrel groups, respectively; adjusted HR: 0.972, 95% CI: 0.321-2.941, P=0.960). Propensity score-matched analysis confirmed such findings.. For patients with bifurcation lesions after PCI, ticagrelor treatment shows lower MACE and MI rates than the clopidogrel one, along with comparable major bleeding.

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Propensity Score; Retrospective Studies; Stroke; Ticagrelor

Patients with acute coronary syndrome (ACS) and previous cardiovascular disease (CVD) (stroke, peripheral arterial disease [PAD] or coronary artery disease [CAD]) are at high risk of serious events and mortality. Current clinical guidelines recommend new antiplatelet drugs (NADs) for high cardiovascular risk patients with ACS; however, these drugs are underused in different scenarios.. This study included 1717 ACS patients from 3 tertiary hospitals. Of them, 641 (37.33%) suffered from previous CVD: 149 patients with stroke, 154 patients with PAD and 541 patients with CAD. Bleeding, mortality and major adverse cardiac events (MACE) at 1 year of follow-up after hospital discharge were analyzed.. NADs administration during hospital stay and at discharge was less frequent in patients with previous CVDs (P<0.001, for both). Cox analysis in this cohort of patients showed that clopidogrel prescription at discharge was independently associated with MACEs (HR: 1.59 [95% CI: 1.03-2.45]; P=0.036) and with death (HR: 1.99 [95% CI: 1.00-3.98]; P=0.049) in multivariate analysis. More specifically, when ticagrelor prescription at discharge was compared with clopidogrel, a significant death reduction was found in both, the univariate and the multivariate Cox analysis (HR: 4.54 [95% CI: 2.26-9.13]; P<0.001 and HR: 2.61 [95% CI: 1.16-5.90]; P=0.021, respectively).. New antiplatelet drugs, especially ticagrelor, showed lower rates of mortality in patients with CVD without differences for bleeding. Despite the recommendations of current clinical guidelines for high risk patients with ACS, the use of NADs is very low in "real-life" patients with previous CVD.

Topics: Acute Coronary Syndrome; Aftercare; Clopidogrel; Comorbidity; Coronary Disease; Drug Utilization; Female; Follow-Up Studies; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Metabolic Syndrome; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proportional Hazards Models; Prospective Studies; Smoking; Spain; Stroke; Tertiary Care Centers; Ticagrelor

Ticagrelor is an oral, reversible, direct-acting P2Y. YINGLONG, a single-arm, phase-IV, 1-year, non-interventional study, described the safety of ticagrelor 90 mg twice daily in Chinese patients (≥ 18 years) with ACS treated with ≥ 1 dose of ticagrelor. Primary outcomes were the incidence of adverse events (AEs), in particular, PLATelet inhibition and patient Outcomes (PLATO)-defined bleeding AEs, and other serious AEs during the 1-year follow-up. Key secondary outcomes were the incidence of major cardiovascular events.. Patients (n = 1041, median age 61.0 years) had started ticagrelor and had post-dose data. Median duration of ticagrelor treatment was 357 days; 577 patients (55.4%) completed 1-year ticagrelor treatment; 973 patients (93.5%) completed 1-year follow-up. Overall, 38.7% of patients reported an AE during treatment. The most common AEs were dyspnea (n = 37, 3.6%), petechiae (n = 30, 2.9%), and chest discomfort (n = 28, 2.7%). Serious AEs, excluding bleeding, were reported in 9.8% of patients during treatment. Incidence of PLATO-defined major bleeding events was 1.1% (n = 11). Of the 21 deaths that occurred during the study (8 post-treatment), 1 was a fatal bleed. Major cardiovascular events were reported in 37 patients (3.6%).. Ticagrelor was well tolerated with a low rate of PLATO-defined major bleeding events in Chinese ACS patients. Safety results were consistent with the known ticagrelor profile.. ClinicalTrials.gov identifier, NCT02430493.. AstraZeneca Investment (China) Co., Ltd.

Topics: Acute Coronary Syndrome; China; Cohort Studies; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors; Ticagrelor; Treatment Outcome

Topics: Aged; Alleles; Aspirin; Clopidogrel; Cytochrome P450 Family 4; Female; Genotype; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Postoperative Complications; Stents; Ticagrelor

Aim of the present study was to investigate the frequency and predictors of premature discontinuation or switch of ADP receptor blockers and its association with serious adverse events. For this purpose 571 consecutive ACS patients receiving ticagrelor (n = 258, 45%) or prasugrel (n = 313, 55%) undergoing PCI were enrolled in this prospective, observational, multicenter ATLANTIS-SWITCH substudy. Predictors of premature discontinuation or switch of antiplatelet therapy and their association with major adverse cardiovascular events and TIMI bleeding events were evaluated. Premature stop/switch was found in 72 (12.6%) patients: 34 (5.9%) stopped and 38 (6.7%) switched the ADP blocker. Ticagrelor treated patients were significantly more likely to stop/switch therapy as compared to prasugrel (15.9% vs. 9.2%, p = 0.016). We identified 4 independent predictors for stop/switch of ADP blocker: major surgery, need for oral anticoagulation (OAC), TIMI major bleeding and drug intolerance. TIMI major bleeding was a driver of stop/switch actions and occurred in 4.3% vs 0.2% in patients with vs without stop/switch (p = 0.001). The majority of stop/switch actions (75%) were physicians driven decisions. Importantly, stop/switch of therapy was not associated with increased risk of MACE (p = 0.936). In conclusion premature switch/stop of ADP blockers appears to be safe when mainly driven by physician's decision and clinical indication.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Drug Administration Schedule; Drug Substitution; Drug-Eluting Stents; Female; Hemorrhage; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prognosis; Prospective Studies; Purinergic P2Y Receptor Antagonists; Registries; Risk Factors; Ticagrelor

In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15-16% in stable patients with a prior myocardial infarction (MI) 1-3 years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60 mg b.i.d. initiated up to 2 years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment.. Of the 21 162 patients enrolled in PEGASUS-TIMI 54, 10 779 patients were included in the primary analysis for this study, randomized to ticagrelor 60 mg (n = 5388) or matching placebo (n = 5391). The cumulative proportions of patients with events at 36 months were calculated by the Kaplan-Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70-0.91; P = 0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67-0.96; P = 0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65-3.39; P < 0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68-2.01; P = 0.58).. In PEGASUS-TIMI 54, treatment with ticagrelor 60 mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60 mg in this population.. http://www.clinicaltrials.gov NCT01225562.

Topics: Aged; Aspirin; Drug Approval; Drug Labeling; Drug Therapy, Combination; Europe; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Recurrence; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Despite great advances with the introduction of ticagrelor and prasugrel in the treatment of acute coronary syndromes (ACS), the risk of thrombosis and bleeding remains significant and affects the choice of clinicians in the treatment of the single patient. Large registries are effective tools to explore patterns of drug administration and adherence to guideline recommendations in real-world clinical practice.. START- antiplatelet is a prospective, observational registry carried out by seven Italian cardiology institutions on patients admitted for ACS aimed to document the real world treatment of ACS patients, adding also data on 12-month follow-up. We present data on the first 1050 patients who have completed 1-year follow-up on a total of 1537 patients. Primary end-points were: 1) MACCE (Major Adverse Cardiovascular and Cerebrovascular Events) including all-cause and cardiovascular mortality, non fatal MI, urgent revascularization, TIA and ischemic stroke; 2) Major and minor bleeding according to TIMI, GUSTO and ISTH classifications.. The dual antiplatelet treatment most prescribed was aspirin plus ticagrelor (47.9%) and aspirin plus clopidogrel (32.1%). At a mean follow-up was 335±131 days, both ticagrelor and prasugrel are associated with a statistically significant reduced total and cardiovascular mortality. Both prasugrel and ticagrelor do not show a significant increased incidence of major and minor bleedings with respect to clopidogrel. Patients with monotherapy had significantly higher incidence of both ischemic stroke and major bleedings.. The analysis of the register has documented that both ticagrelor and prasugrel are associated with a statistically significant reduced total and cardiovascular mortality but both do not show a significant increased incidence of major and minor bleedings with respect to clopidogrel.

Topics: Acute Coronary Syndrome; Aged; Cardiovascular Diseases; Cerebrovascular Disorders; Female; Follow-Up Studies; Hemorrhage; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Registries; Risk; Stroke; Thrombosis; Ticagrelor; Treatment Outcome

Background Prior reports indicate that the effect of P2Y

Topics: Acute Coronary Syndrome; Aged; Angina, Unstable; Asian People; Cardiovascular Diseases; Cause of Death; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Prasugrel Hydrochloride; Proportional Hazards Models; Purinergic P2Y Receptor Antagonists; Recurrence; Republic of Korea; Stroke; Ticagrelor; Treatment Outcome

To compare the effectiveness and safety of ticagrelor versus prasugrel in preventing recurrent cardiovascular disease (CVD) and major bleeding events in patients with acute coronary syndrome (ACS).. Retrospective cohort analysis.. Truven Commercial and Medicare Supplemental claims database (2011-2016).. Study consisted of adults with ACS who newly initiated ticagrelor or prasugrel within 7 days of their first ACS diagnosis and had no prior use for at least 12 months; after propensity score matching, 10,073 patients were in each group.. The primary study outcomes, first occurrence of a recurrent nonfatal CVD event (composite of myocardial infarction and stroke) and occurrence of a major bleeding event, were compared between the ticagrelor and prasugrel groups. Secondary outcomes included occurrence of minor bleeding events, defined based on the presence of bleeding events in outpatient claims. Cox proportional hazards models after propensity score matching were used to obtain the hazard ratio (HR) and 95% confidence interval (CI). In the Cox proportional hazards model, the use of ticagrelor was associated with a decreased risk of recurrent nonfatal CVD events (HR 0.80, 95% CI 0.70-0.92) and major bleeding events (HR 0.54, 95% CI 0.41-0.70) compared with prasugrel. Additionally, the use of ticagrelor was associated with a lower risk of minor bleeding events compared with prasugrel (HR 0.71, 95% CI 0.65-0.78).. In this population-based cohort of incident ACS patients, ticagrelor was associated with a reduced rate of recurrent nonfatal CVD events, major and minor bleeding events compared with prasugrel.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Comorbidity; Female; Hemorrhage; Humans; Insurance Claim Review; Male; Medicare; Middle Aged; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Propensity Score; Proportional Hazards Models; Retrospective Studies; Secondary Prevention; Sex Factors; Ticagrelor; United States

Ticagrelor induces more potent platelet reactivity (PR) inhibition with reduced interindividual variability compared to clopidogrel. Although on-clopidogrel PR was shown to correlate with ischemia and bleeding events, no study has investigated the relationship between on-ticagrelor PR and outcome.. We aimed to evaluate the relationship between on-ticagrelor PR, assessed by the vasodilator-stimulated phosphoprotein index (VASP), and thrombotic and bleeding events in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI).. We performed a prospective, multicenter observational study on patients treated with PCI for ACS. The VASP index was used to assess PR after ticagrelor loading dose (LD). The primary endpoint was the link between major adverse cardiovascular events (MACE) and PR.. Among the 530 patients with ACS included, 183 (34.5%) were admitted for ST elevation myocardial infarction. We observed high potency and limited interindividual variability after the ticagrelor LD (VASP 19.1% ± 16.6%). At 1 month, 21 (3.8%) MACE and 29 (5.5%) bleedings ≥ 2 according to the Bleedings Academic Research Consortium (BARC) scale were recorded. Neither MACE nor bleeding was associated with PR (P = .34 and P = .78, respectively). However, there was a strong association between PR and the occurrence of definite acute stent thrombosis (P = .03). Platelet reactivity was the only factor associated with acute definite stent thrombosis.. In patients receiving a ticagrelor LD while undergoing PCI for ACS, PR using the VASP did not predict MACE or bleeding, but it was significantly associated with the occurrence of definite acute stent thrombosis.

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Blood Platelets; Cell Adhesion Molecules; Coronary Thrombosis; Female; France; Hemorrhage; Humans; Male; Microfilament Proteins; Middle Aged; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention; Phosphoproteins; Platelet Activation; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors; ST Elevation Myocardial Infarction; Stents; Ticagrelor; Time Factors; Treatment Outcome

Topics: Acute Coronary Syndrome; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Labeling; Drug Monitoring; Dual Anti-Platelet Therapy; Genotype; Hemorrhage; Humans; Percutaneous Coronary Intervention; Pharmacogenomic Testing; Platelet Aggregation Inhibitors; Platelet Function Tests; Practice Guidelines as Topic; Prasugrel Hydrochloride; Ticagrelor

We compared the clinical outcome of diabetic versus nondiabetic patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in the GReek AntiPlatElet (GRAPE) registry.. GRAPE is a prospective observational study, focusing on contemporary antiplatelet use in moderate-risk to high-risk ACS patients receiving PCI. Major adverse cardiovascular events (MACE), (composite of death, nonfatal myocardial infarction, urgent revascularization, and stroke) and bleeding events (Bleeding Academic Research Consortium definition) at 1 year of follow-up were analyzed using propensity score adjustment. A subanalysis according to diabetes mellitus (DM) status was performed.. Out of 2047 registered patients, 469 (22.9%) were diabetic. Complete 1-year follow-up was available in 95.1% of patients. MACE occurred in 12.2 and 7.2% of those patients with and without DM, respectively [adjusted hazard ratio (HR), 95% confidence interval (CI)=1.27 (0.89-1.79), P=0.2]. Observed BARC type ≥3 bleeding risk was not higher in diabetic patients: adjusted HR (95% CI)=1.20 (0.79-1.84). In the subgroup of clopidogrel-treated patients (N=238), MACE rate was significantly higher in diabetic compared with nondiabetic cohort [13.4 vs. 9%, adjusted HR (95% CI)=1.68 (1.07-2.64), P=0.03]. In the subgroup of ticagrelor-treated or prasugrel-treated patients (N=228), MACE rate did not differ significantly between diabetic and nondiabetic patients: 9.6 versus 5%, adjusted HR (95% CI)=1.35 (0.77-2.37), P=0.38.. In 'real-life' ACS undergoing PCI, diabetic patients have higher - although not significantly - MACE rate and no difference in bleeding events. This difference in MACE was significant among clopidogrel-treated patients, whereas when newer antiplatelet agents were used the negative impact of DM on ischemic events was eliminated.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Case-Control Studies; Clopidogrel; Cohort Studies; Comorbidity; Diabetes Mellitus; Female; Greece; Hemorrhage; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Myocardial Revascularization; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Propensity Score; Proportional Hazards Models; Prospective Studies; Stroke; Ticagrelor; Ticlopidine

There are few data on ticagrelor in Asian patients. This study evaluated clinical outcomes with ticagrelor and clopidogrel in Taiwanese patients with acute myocardial infarction (AMI).Methods and Results:We used the Taiwan National Health Insurance Research Database to identify 27,339 AMI patients aged ≥18 years between January 2012 and December 2014, and only patients who survived greater than or equal to 30 days after AMI and took dual antiplatelet therapy were included. Cohorts of ticagrelor and clopidogrel were matched 1:8, based on propensity score matching, to balance baseline covariates. The primary efficacy endpoints were death from any cause, AMI, or stroke. The safety endpoints consisted of major gastrointestinal bleeding or intracerebral hemorrhage. Following propensity matching, the primary efficacy endpoint rate was 22% lower in the ticagrelor group than in the clopidogrel group (10.6% and 16.2%, respectively; adjusted HR, 0.779; 95% CI: 0.684-0.887). The safety endpoint rate was similar between the ticagrelor and clopidogrel groups (3.2% and 4.1% respectively; adjusted HR, 0.731; 95% CI: 0.522-1.026).. In real-world AMI Taiwanese patients, ticagrelor seemed to offer better anti-ischemic protection than clopidogrel, without an increase in the rate of major bleeding. A large-scale randomized trial is needed to assess the efficacy and safety of ticagrelor in East Asian AMI patients.

Topics: Aged; Asian People; Cardiovascular Diseases; Clopidogrel; Hemorrhage; Humans; Ischemia; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Propensity Score; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Risk; Taiwan; Ticagrelor; Treatment Outcome

Acute coronary syndrome (ACS) guidelines recommend the use of newer P2Y. Retrospective analysis of a multicenter ACS registry; 3515 consecutive patients were included. The association between risk scores and prescription of newer P2Y. A total of 1021 patients (29%) were treated with prasugrel or ticagrelor. On multivariate analyses, both GRACE (OR per 10 points, 0.89; 95%CI, 0.86-0.92; P < .001) and CRUSADE (OR per 10 points, 0.96; 95%CI, 0.94-0.98; P < .001) risk scores were inversely associated with the use of newer P2Y. New P2Y

Topics: Acute Coronary Syndrome; Adenosine; Aged; Drug Prescriptions; Female; Hemorrhage; Hospitalization; Humans; Male; Myocardial Ischemia; Patient Discharge; Practice Patterns, Physicians'; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Registries; Retrospective Studies; Risk Assessment; Ticagrelor

No direct comparisons of ticagrelor and prasugrel with 1-year clinical follow-up have been reported.. Our objective was to compare 1-year clinical outcomes among patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with either ticagrelor or prasugrel in a real-world setting.. This retrospective study included patients from a payer database who were aged ≥18 years and had ACS managed with PCI with no history of transient ischemic attack (TIA)/stroke. Data were propensity matched for prasugrel use with a 3:1 prasugrel:ticagrelor ratio. Post-discharge net adverse clinical event (NACE) rate at 1 year was evaluated for noninferiority using a pre-defined 20% margin. NACE was a composite of major adverse cardiovascular events (MACE) or rehospitalization for bleeding.. In total, 15,788 ACS-PCI patients were included (prasugrel 12,797; ticagrelor 2991). Prasugrel-treated patients were younger; less likely to be female, have prior myocardial infarction (MI), diabetes, or non-ST-segment elevation MI (NSTEMI); and more likely to have unstable angina (UA) than ticagrelor-treated patients. Prior to matching, NACE and MACE (P < 0.01) were lower, with no difference in bleeding with prasugrel compared with ticagrelor. After matching, there was no significant difference in baseline characteristics. Noninferiority was demonstrated for NACE, MACE, and bleeding between prasugrel and ticagrelor. NACE and MACE were significantly lower with prasugrel use, primarily driven by heart failure, with no significant difference in all-cause death, MI, UA, revascularization, TIA/stroke, or bleeding.. In this retrospective study, physicians preferentially used prasugrel rather than ticagrelor in younger ACS-PCI patients with lower risk of bleeding or comorbidities. After propensity matching, clinical outcomes associated with prasugrel were noninferior to those with ticagrelor.

Topics: Acute Coronary Syndrome; Adenosine; Databases, Factual; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Propensity Score; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Ticagrelor; Treatment Outcome

The objective of this study is to evaluate the effects of cytochrome P450 2C19 (CYP2C19) polymorphism on adverse cardiovascular events (MACE) in Hakka patients with acute coronary syndrome (ACS) receiving clopidogrel who had undergone coronary drug-eluting stent placement after percutaneous coronary intervention (PCI) in southern China.. Genotyping of CYP2C19 and MACE of 934 ACS patients with PCI on clopidogrel maintenance therapy were analyzed. Patients who carried loss-of-function CYP2C19 were treated with a 150-mg maintenance dose of clopidogrel or 90 mg of ticagrelor antiplatelet therapy, and patients who were non-carriers received clopidogrel therapy daily at a maintenance dose of 75 mg and the patients were followed-up for at least 12 months. The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, and target vessel revascularization and stroke.. The allelic frequency of CYP2C19*2 and CYP2C19*3 of Hakka patients in the current study was 31.64 and 5.19%, respectively. The CYP2C19 wild-type homozygotes (*1/*1) were the most predominant among the patients (40.36%), followed by the CYP2C19*2 heterozygotes (*1/*2) (40.26%). The distribution of CYP2C19 phenotypes was divided into extensive metabolizers (EM; 40.36%), intermediate metabolizers (IM; 45.61%), and poor metabolizers (PM; 14.03%). Based on the genotype-guided antiplatelet therapy, there was no significant association between the carrier status and the clinical outcome at 1, 6, and 12 months. In addition, no significant difference in the rates of bleeding was found among the three groups. After logistic regression analysis, hypertension was the only independent predictor of cardiovascular events (relative risk, 1.501; 95% CI, 1.011 to 2.229; P = 0.044).. Our results shed new light on the important benefit of testing CYP2C19 polymorphisms before prescribing clopidogrel in patients treated with drug-eluting stent implantation after PCI. The testing may help to optimize pharmacotherapy effectiveness by providing individualized treatment to the Chinese population. Our findings mandate further studies aimed at initiating genome-based personalized antiplatelet therapy in a Hakka population in southern China.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Asian People; Chi-Square Distribution; China; Clinical Decision-Making; Clopidogrel; Cytochrome P-450 CYP2C19; Drug-Eluting Stents; Female; Gene Frequency; Genetic Predisposition to Disease; Hemorrhage; Heterozygote; Homozygote; Humans; Hypertension; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Pharmacogenetics; Pharmacogenomic Variants; Phenotype; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Precision Medicine; Retrospective Studies; Risk Factors; Stroke; Ticagrelor; Ticlopidine; Treatment Outcome

The HEAT-PPCI trial compared bivalirudin and unfractionated heparin in patients undergoing primary percutaneous coronary intervention (PPCI). The aim of this study was to report pre-specified, secondary analyses comparing the effects of P2Y12 inhibiting agents on platelet reactivity and clinical events.. All patients received preprocedural oral antiplatelet therapy. During the early stages of the trial, the P2Y12 inhibitor of choice was prasugrel with some use of clopidogrel. Later, routine therapy switched to ticagrelor. For cases performed during working hours, multiple electrode aggregometry (MEA) was used to assess ADP-induced platelet aggregation at the end of the index procedure. The effect of P2Y12 inhibitors on the primary efficacy (major adverse cardiac events [MACE]) and safety (major bleeding) outcomes was assessed in all patients. Multiple logistic regression was used to adjust for differences in baseline characteristics. With MEA data from 469 patients, prasugrel therapy resulted in significantly greater suppression of ADP-induced platelet aggregation at 40 U (23, 78) (median; interquartile range [IQR]) when compared against ticagrelor 75 U (41, 100.75); p<0.001 or clopidogrel 79 U (56, 96); p<0.001. In the entire study population (N=1,803), prasugrel therapy was associated with significantly fewer MACE (26/497; 5.2%) in comparison to ticagrelor (83/1,123; 7.4%) or clopidogrel (18/183; 9.8%); odds ratio (OR) 0.64, confidence interval (CI): 0.41-0.99, p=0.045. For major bleeding, there were no significant differences among the three groups - clopidogrel (3/183; 1.6%), prasugrel (13/497; 2.6%) and ticagrelor (43/1,123; 3.8%); OR 0.73, CI: 0.39-1.35, p=0.31. Patients treated with clopidogrel had more high-risk features and clopidogrel use was more common as an alternative to prasugrel. After adjustment, there were no significant differences in the rates of MACE (OR 0.70, CI: 0.41-1.21, p=0.20) or major bleeding (OR 0.80, CI: 0.41-1.60, p=0.53).. In HEAT-PPCI, patients who received prasugrel (rather than clopidogrel or ticagrelor) had significantly greater suppression of ADP-induced platelet aggregation at the end of the procedure. After adjustment for differences in baseline characteristics, there were no significant differences in ischaemic or bleeding outcomes among the antiplatelet therapies.

Topics: Anticoagulants; Clopidogrel; Coronary Thrombosis; Hemorrhage; Humans; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

This study aims to evaluate outcomes associated with different P2Y12 agents in Saphenous Vein graft (SVG) percutaneous coronary intervention (PCI).. SVG PCI is associated with greater risks of ischemic complications, compared with native coronary PCI. Outcomes associated with the use of potent P2Y12 blocking drugs, Prasugrel and Ticagrelor, in SVG PCI are unknown.. Patients included in the study underwent SVG PCI in the United Kingdom between 2007 and 2014 for acute coronary syndrome and were grouped by P2Y12 antiplatelet use. In-hospital major adverse cardiac events, major bleeding and 30-day and 1-year mortality were examined. Multiple imputations with chained equations to impute missing data were used. Adjustment for baseline imbalances was performed using (1) multiple logistic regression (MLR) and (separately) (2) propensity score matching (PSM).. Data weres analyzed from 8,119 patients and most cases were treated with Clopidogrel (n = 7,401), followed by Ticagrelor (n = 497) and Prasugrel (n = 221). In both MLR and PSM models, there was no significant evidence to suggest that either Prasugrel or Ticagrelor was associated with significantly lower 30-day mortality compared with Clopidogrel. The odds ratios reported from the multivariable analysis were 1.22 (95% CI: 0.60-2.51) for Prasugrel vs. Clopidogrel and 0.48 (95% CI: 0.20-1.16) for Ticagrelor vs. Clopidogrel. No significant differences were seen for in-hospital ischemic or bleeding events.. Our real world national study provides no clear evidence to indicate that use of potent P2Y12 blockers in SVG PCI is associated with improved clinical outcomes.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Clopidogrel; Coronary Artery Bypass; Databases, Factual; Female; Graft Occlusion, Vascular; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Registries; Retrospective Studies; Risk Factors; Saphenous Vein; Ticagrelor; Time Factors; Treatment Outcome; United Kingdom

Preload with clopidogrel, ticagrelor, or prasugrel in the setting of ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) is frequently applied. Limited data are available regarding the outcome impact of pretreatment with these drugs in the real world.. The outcome of 760 STEMI patients treated by primary PCI receiving clopidogrel, prasugrel, or ticagrelor (n = 269, 327, 164, respectively) was evaluated. Patients in the clopidogrel group were older, whereas those in the ticagrelor group had less hypertension but were more active smokers. Angiographic characteristics were comparable among the three groups. At 1 month, more events were observed in the clopidogrel group (11.1%) than in the ticagrelor and prasugrel groups (7.1 vs. 5.1%, P = 0.025), whereas the number of events in the ticagrelor and prasugrel groups did not differ. At 1 year, similar differences existed, mainly driven by a higher rate of death (19.5%, P = 0.008) or stent thrombosis (2 vs. 1.3% for ticagrelor, P = 0.132; vs. 0.3% for prasugrel, P = 0.07) in the clopidogrel group. In-hospital and 1-year bleeding rates were similar between groups.. In real-world practice, pretreatment with prasugrel or ticagrelor in ongoing STEMI treated by primary PCI seems to be a well tolerated alternative strategy compared with clopidogrel but provides superior benefit in terms of outcomes.

Topics: Aged; Belgium; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Multivariate Analysis; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Preoperative Care; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Stents; Survival Analysis; Thrombosis; Ticagrelor; Time Factors; Treatment Outcome

We aimed to analyse outcomes of ticagrelor and clopidogrel stratified by estimated glomerular filtration rate (eGFR) in a large unselected cohort of patients with acute myocardial infarction (MI).. We used follow-up data in MI survivors discharged on ticagrelor or clopidogrel enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry. The association between ticagrelor versus clopidogrel and the primary composite outcome of death, MI or stroke and the secondary outcome rehospitalisation with bleeding diagnosis at 1 year, was studied using adjusted Cox proportional hazards models, stratifying after eGFR levels.. In total, 45 206 patients with MI discharged on clopidogrel (n=33 472) or ticagrelor (n=11 734) were included. The unadjusted 1-year event rate for the composite endpoint of death, MI or stroke was 7.0%, 18.0% and 48.0% for ticagrelor treatment and 11.0%, 33.0% and 64.0% for clopidogrel treatment in patients with eGFR. Treatment with ticagrelor as compared with clopidogrel in patients with MI was associated with lower risk for the composite of death, MI or stroke and a higher bleeding risk across all strata of eGFR. Of caution, bleeding events were more abundant in patients with eGFR

Topics: Aged; Clopidogrel; Female; Glomerular Filtration Rate; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Outcome Assessment, Health Care; Platelet Aggregation Inhibitors; Registries; Risk Assessment; Stroke; Sweden; Ticagrelor

Elderly patients with acute coronary syndrome (ACS) are at high risk for ischemic and bleeding events. This study aimed to evaluate the clinical effectiveness and safety of dual loading antiplatelet therapy for patients 75 years and older undergoing percutaneous coronary intervention for ACS.. The Improving Care for Cardiovascular Disease in China-ACS project was a collaborative study of the American Heart Association and Chinese Society of Cardiology. A total of 5887 patients 75 years and older with ACS who had percutaneous coronary intervention and received dual antiplatelet therapy with aspirin and P2Y. A dual loading dose of antiplatelet therapy was associated with increased major bleeding risk but not with decreased major adverse cardiovascular events risk among patients 75 years and older undergoing percutaneous coronary intervention for ACS in China.. URL: http://www.ClinicalTrials.gov. Unique identifier: NCT02306616.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Aged, 80 and over; Aspirin; China; Clopidogrel; Databases, Factual; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Quality Improvement; Registries; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Although ticagrelor has improved clinical outcomes among patients with acute coronary syndrome compared with clopidogrel, adherence to this new antiplatelet agent in real-world practice has not been fully investigated.. Premature ticagrelor cessation in routine clinical practice occurred in 1 of 6 patients and was primarily related to adverse effects among which bleeding and dyspnea were the most frequent. Although premature ticagrelor cessation was not associated with adverse cardiovascular outcomes, this finding requires careful interpretation in view of the modest sample size.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02241291.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Clopidogrel; Drug Administration Schedule; Drug Substitution; Dyspnea; Female; Hemorrhage; Humans; Male; Medication Adherence; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Registries; Switzerland; Tertiary Care Centers; Ticagrelor; Time Factors; Treatment Outcome

Dual antiplatelet therapy (DAPT) is recommended in patients receiving drug-eluting stents (DES). However, bleeding risk should be weighed against ischemic risk. Utility of GRACE risk score and ACUITY-HORIZONS bleeding risk score was assessed in patients with acute myocardial infarction (MI) according to use of P2Y12 blocker.. From the Korea Acute Myocardial Infarction Registry-National Institute of Health database, 7791 patients with acute MI receiving DES were divided into ticagrelor (n=1554) and clopidogrel (n=6237) groups. Propensity-matched 12-month mortality and bleeding event rates were compared according to GRACE and ACUITY-HORIZONS scores. Patients who received thrombolysis, prasugrel or anticoagulants, or who discontinued or switched DAPT were excluded.. In all patients, high-risk patients more often received clopidogrel. After propensity score matching (n=1553 in each group), 12-month mortality was not different, but TIMI major bleeding rate was higher with ticagrelor (2.8% vs. 1.4%, p=0.007). On subgroup analysis, 12-month mortality was lower with ticagrelor in patients with high (>140) compared to low-to-moderate risk GRACE score (5.1% vs. 7.9%, p=0.04). When combined with ACUITY-HORIZONS bleeding score, 12-month mortality was lower with ticagrelor in patients with high GRACE score but without very high (≥20) ACUITY-HORIZONS score (2.4% vs. 5.3%, p=0.03).. In patients with acute MI receiving DES, GRACE and ACUITY-HORIZONS scores may help guide DAPT. In patients with high GRACE score, a more potent P2Y12 blocker may be considered, particularly in the subset not at very high risk of bleeding.

Topics: Aged; Clopidogrel; Decision Support Techniques; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Propensity Score; Registries; Republic of Korea; Risk Assessment; Ticagrelor

The effects of ticagrelor pretreatment in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI) is debated. This study investigated the effects of ticagrelor pretreatment on clinical outcomes in this patient group.. Patients with ST-segment-elevation myocardial infarction undergoing primary PCI were included from October 2010 to October 2014 in Sweden. Screening was done using the SWEDEHEART register (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies). A total of 7433 patients were included for analysis with 5438 patients receiving ticagrelor pretreatment and 1995 patients with ticagrelor given only in the catheterization laboratory. The primary end point of the study was 30-day event rates of a composite of all-cause mortality, myocardial infarction (MI), and stent thrombosis. Secondary end points were mortality, MI, or stent thrombosis alone and major in-hospital bleeding. Crude event rates showed no difference in 30-day composite end point (6.2% versus 6.5%;. Ticagrelor pretreatment versus ticagrelor given in the catheterization laboratory in patients with ST-segment-elevation myocardial infarction undergoing primary PCI did not improve the composite end point of all-cause mortality or MI or stent thrombosis or its individual components at 30 days.

Topics: Aged; Coronary Thrombosis; Drug Administration Schedule; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recurrence; Registries; Risk Factors; ST Elevation Myocardial Infarction; Sweden; Ticagrelor; Time Factors; Treatment Outcome

Little is known about the adherence to dual antiplatelet therapy with ticagrelor and reasons for discontinuation in real life. Therefore, we evaluated the 12-month course of patients with acute coronary syndromes (ACS) treated with percutaneous coronary intervention (PCI) and ticagrelor during the acute phase.. A total of 614 patients included into the prospective ALKK-PCI Registry between 2014 and 2015 surviving for at least 12 months after discharge provided informations about duration of ticagrelor therapy. In total, 133 patients (21.7%) discontinued ticagrelor prematurely: nine patients before discharge and 124 (20.2%) at a mean 131 days after PCI. Independent baseline predictors for early discontinuation were age >75 years, atrial fibrillation, and prior stroke. Side effects such as dypnoea or bradycardias and bleeding leading to a premature discontinuation of ticagrelor were reported in less than 3% and less than 2% of the total patient population, respectively. In 50% of patients, there was no replacement with another platelet inhibitor after early discontinuation of ticagrelor, while in 28.2% it was replaced by clopidogrel. Bleeding events were observed more often (10.4% vs. 2.7%, P < 0.001) and coronary artery bypass grafting (CABG) (5.3% vs. 0, 4%, P < 0.001) was performed more often in patients with early discontinuation.. In this real-life experience of ticagrelor in patients with ACS 22% of patients discontinued ticagrelor early. Side effects were the cause for discontinuation in only 3%, while age >75 years, prior stroke, atrial fibrillation, CABG, and bleeding during follow-up were associated with premature discontinuation.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Drug Substitution; Drug Therapy, Combination; Female; Germany; Hemorrhage; Humans; Male; Medication Adherence; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Registries; Retrospective Studies; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Topics: Chest Pain; Diagnosis, Differential; Hemorrhage; Humans; Lung Diseases; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; ST Elevation Myocardial Infarction; Ticagrelor; Tomography, X-Ray Computed

Prasugrel and ticagrelor are recommended over clopidogrel in patients with ST-elevation myocardial infarction (STEMI). In this registry analysis, we compared efficacy and safety of ticagrelor and prasugrel P2Y12 inhibition in patients with STEMI. We included 318 patients in this single-center analysis. Twelve-month follow-up was conducted during ambulatory care at our department. Patients were on dual antiplatelet therapy with aspirin and ticagrelor or prasugrel during the follow-up period. Prescription of prasugrel or ticagrelor, respectively, was according to the preference of the treating physician. Major adverse cardiac and cerebrovascular events (MACCE) [death, myocardial infarction (MI), stroke, and unplanned reintervention] and thrombolysis in myocardial infarction (TIMI) bleeding (major/minor) were registered during hospitalization and follow-up. TIMI bleeding events were more frequent in ticagrelor-treated patients [17 vs. 5 patients, hazard ratio (HR) 2.85, 95% confidence interval (CI) 1.2-6.6; log-rank P value = 0.01]. Prasugrel-treated patients were significantly younger (ticagrelor 63 ± 12 years vs. prasugrel 57 ± 10; P < 0.0001). Besides that, patients' characteristics were similar in both groups. Multivariate analysis revealed that ticagrelor medication was independently associated with bleeding risk after adjustment for age, percutaneous coronary intervention approach (femoral vs. radial), diabetes mellitus, and kidney function (HR 3.01; 95% CI 1.0-7.4; P = 0.043). In patients treated with ticagrelor, 35 MACCE were detected. There was no difference as compared to prasugrel-treated patients (24 events, HR 1.24, 95% CI 0.79-2.09; log-rank P value = 0.41). TIMI bleeding events were more frequent in ticagrelor-treated patients with STEMI during 12-month follow-up. There were no differences in MACCE between groups in this registry analysis.

Topics: Aged; Aspirin; Drug Therapy, Combination; Female; Germany; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Pilot Projects; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Recurrence; Registries; Risk Factors; ST Elevation Myocardial Infarction; Stroke; Ticagrelor; Time Factors; Treatment Outcome

There was still conflict on the antithrombotic advantage of ticagrelor versus clopidogrel among East Asian population with acute coronary syndrome (ACS). We considered that the baseline bleeding risk might be an undetected key factor that significantly affected the efficacy of ticagrelor.. A total of 20,816 serial patients who underwent percutaneous coronary intervention (PCI) from October 2011 to August 2014 in the General Hospital of Shenyang Military Region were enrolled in the present study. Patients receiving ticagrelor or clopidogrel were further subdivided according to basic bleeding risk. The primary outcome was net adverse clinical events (NACEs) defined as major adverse cardiac or cerebral events (MACCE, including all-cause death, myocardial infarction, ischemia-driven target vessel revascularization, or stroke) and any bleeding during 1-year follow-up. Comparison between ticagrelor and clopidogrel was adjusted by propensity score matching (PSM).. Among the 20,816 eligible PCI patients who were included in this study, there were 1578 and 779 patients in the clopidogrel and ticagrelor groups, respectively, after PSM, their clinical parameters were well matched. Patients receiving ticagrelor showed comparable NACE risk compared with those treated by clopidogrel (5.3% vs. 5.1%, P = 0.842). Furthermore, ticagrelor might reduce the MACCE risk in patients with low bleeding risk but increase MACCE in patients with moderate-to-high bleeding potential (ticagrelor vs. clopidogrel, low bleeding risk: 2.5% vs. 4.9%, P = 0.022; moderate-to-high bleeding risk: 4.8% vs. 3.0%, P = 0.225; interaction P = 0.021), with vast differences in all bleeding (low bleeding risk: 1.5% vs. 0.8%, P = 0.210; moderate-to-high bleeding risk: 4.8% vs. 3.0%, P = 0.002; interaction P = 0.296).. Among real-world Chinese patients with ACS treated by PCI, ticagrelor only showed superior efficacy in patients with low bleeding risk but lost its advantage in patients with moderate-to-high bleeding potential.

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Ticlopidine; Treatment Outcome

To evaluate "real life" incidence and independent predictors of major bleeding defined in ACS patients treated with PCI and current standard antithrombotic therapy with prasugrel or ticagrelor.. The RENAMI project is a multicenter retrospective observational registry enrolling 4424 patients with ACS treated with PCI and prasugrel or ticagrelor plus aspirin. Primary endpoint was MACE (major adverse cardiovascular events). Secondary endpoints included each component of MACE, cardiovascular death (CV death), recurrence of ACS (reACS) and stroke. Eighty three (1.8%) patients developed out of hospital major bleedings after 14.1 ± 6.2 months. These patients had higher rates of MACE (14.5% vs 4.4%; p = 0.001) and of all-cause death (11% vs 2.1%; p < 0.001). Independent predictors of major bleeding were age >75 years (OR 2.00; 95% CI 1.18-3.41; p = 0.010) and female sex (OR 1.66; 95% CI 1.02-2.70; p = 0.041). BARC 3-5 bleeding was independently associated with all-cause mortality (OR 3.46; 95% CI 1.64-7.31; p 0.001).. In ACS patients treated with PCI and ticagrelor or prasugrel, BARC 3-5 bleedings despite being uncommon negatively impacted on prognosis. Old and female patients are at increased risk, offering clinical indications for tailoring dual antiplatelet therapy.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Cohort Studies; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Predictive Value of Tests; Registries; Retrospective Studies; Risk Factors; Ticagrelor; Treatment Outcome

Comparative outcomes of treatment with antiplatelet drugs in patients with acute coronary syndrome (ACS) and co-morbid diabetes mellitus (DM) are not well studied.. We performed a cohort study using US commercial claims data (2009-2015) and conducted the following pairwise comparisons in ACS patients with DM: prasugrel vs clopidogrel, ticagrelor vs clopidogrel, and prasugrel vs ticagrelor. Outcomes of interest included (1) a composite effectiveness endpoint including myocardial infarction, ischemic stroke, or inpatient mortality; (2) a composite safety endpoint including major bleeding events requiring hospitalization; and (3) pneumonia hospitalizations as a negative control endpoint. We used calendar time-specific propensity score matching to account for confounding and applied Cox proportional hazard models to calculate hazard ratios (HR) with 95% confidence intervals (CI).. Comparative risk of the effectiveness endpoint was lower among prasugrel initiators compared to clopidogrel initiators (HR 0.82, 95% CI 0.68-0.99, N = 7011 matched pairs), but no different between ticagrelor and clopidogrel (HR 1.02, 95% CI 0.76-1.37, N = 3013 pairs) or prasugrel and ticagrelor (HR 0.83, 95% CI 0.58-1.18, N = 2207 pairs). Bleeding risk was higher among prasugrel initiators when compared to clopidogrel initiators within the first month of treatment (HR 1.85, 95% CI 1.03-3.35); no other comparison indicated any difference. No differences in the negative control outcomes were noted after PS matching for all comparisons, indicating adequate confounding control.. Prasugrel was associated with superior cardiovascular outcomes and a higher risk of short-term bleeding compared to clopidogrel in patients with ACS and DM. Comparative outcomes were similar between ticagrelor and clopidogrel or prasugrel and ticagrelor.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Cohort Studies; Comorbidity; Comparative Effectiveness Research; Diabetes Mellitus; Female; Hemorrhage; Hospital Mortality; Hospitalization; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Stroke; Ticagrelor; Treatment Outcome; United States

Dual antiplatelet therapy (DAPT) helps prevent ischemic events after coronary stenting but comes with an increased risk of bleeding. Several risk scores have been proposed for the management of patients receiving DAPT, but no standardized tool exists for the purpose. We sought to compare the performance of the new PRECISE-DAPT (Predicting Bleeding Complication in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy), CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines), and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) scores for the prediction of bleeding in Korean patients receiving DAPT.. Nine hundred and four consecutive patients who underwent stent implantation received DAPT. One-year bleedings were assessed using TIMI (Thrombolysis in Myocardial Infarction), GUSTO (Global Use of Strategies to Open Occluded Arteries), and BARC (Bleeding Academic Research Consortium). Bleeding events occurred in 154 patients (17.0%) by BARC type ≥3a criteria, 119 patients (13.2%) by the TIMI minor or major criteria, and 80 patients (8.8%) by the GUSTO moderate or severe criteria. In the C statistic analysis, CRUSADE, ACUITY, and PRECISE-DAPT scores showed high area under the curve values for 1-year bleeding (area under the curve 0.73, 0.75, and 0.75 for TIMI minor or major bleeding; area under the curve 0.81, 0.79, and 0.82 for GUSTO moderate to severe; and area under the curve 0.79, 0.81, and 0.81 for BARC type ≥3a, respectively). The discriminate ability of PRECISE-DAPT was similar to CRUSADE and ACUITY in bleeding complications. However, the PRECISE-DAPT score was better at reclassifying the risk of 1-year bleeding compared with ACUITY for the 3 bleeding criteria.. The PRECISE-DAPT score is a simple 5-item risk score that represents a standardized tool for the prediction of 1-year bleeding in Korean patients receiving DAPT, regardless of bleeding definition.

Topics: Aged; Aspirin; Clopidogrel; Decision Support Techniques; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Predictive Value of Tests; Purinergic P2Y Receptor Antagonists; Republic of Korea; Retrospective Studies; Risk Assessment; Risk Factors; Stents; Ticagrelor; Treatment Outcome

Essentials MEDI2452 is a specific antidote of the platelet P2Y. Background Ticagrelor, a P2Y

Topics: Adenosine; Adenosine Diphosphate; Animals; Antibodies, Neutralizing; Antidotes; Aspirin; Biotinylation; Blood Pressure; Broadly Neutralizing Antibodies; Hemorrhage; Hemostasis; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Swine; Ticagrelor; Time Factors

We sought to describe trends in the use of preprocedural P2Y12 inhibitors and their clinical impact in patients undergoing percutaneous coronary intervention (PCI).. Oral P2Y12 inhibitors are ubiquitously used medications; however, the specific timing of initial P2Y12 inhibitor administration remains intensely debated.. Our study population comprised 74,053 consecutive patients undergoing PCI at 47 hospitals in Michigan from January 2013 through June 2015. In-hospital outcomes included stent thrombosis, bleeding, need for transfusion, and death. Hierarchical logistic regression, propensity matching, and targeted maximum likelihood estimation were used to adjust for baseline patient differences and clustering, and to minimize bias.. Of 24,733 patients who received a preprocedural P2Y12 inhibitor, 82% received clopidogrel, 8% prasugrel, and 10% ticagrelor. Preprocedural administration of P2Y12 inhibitors declined during the study (49.3% to 24.8%; P<.001), and varied greatly across hospitals (14.5%-95.9%). No significant differences in outcomes were observed between patients receiving preprocedural clopidogrel and a matched cohort of those not receiving any preprocedural P2Y12 inhibitor (stent thrombosis: adjusted odds ratio [OR], 1.55; 95% confidence interval [CI], 0.30-7.84; bleeding: OR, 0.96; 95% CI, 0.63-1.46; transfusion: OR, 1.03; 95% CI, 0.69-1.55; and death: OR, 0.95; 95% CI, 0.38-2.37). Similar findings were demonstrated for preprocedural ticagrelor and prasugrel. Results from a subgroup analysis of patients with non-ST segment elevation acute coronary syndrome (n = 28,072) were consistent with the overall findings.. There was a substantial decline in the rate of preprocedural P2Y12 inhibitor administration during the study. Furthermore, there were no significant differences in outcomes between patients treated with preprocedural P2Y12 inhibitors and those who were not.

Topics: Adenosine; Aged; Blue Cross Blue Shield Insurance Plans; Clopidogrel; Drug Utilization Review; Ethnicity; Female; Graft Occlusion, Vascular; Hemorrhage; Hospital Mortality; Humans; Male; Michigan; Middle Aged; Outcome and Process Assessment, Health Care; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Preoperative Period; Purinergic P2Y Receptor Antagonists; Stents; Ticagrelor; Ticlopidine; Time Factors

Dual antiplatelet therapy is a mainstay of care for percutaneous coronary intervention (PCI) patients; however, uncertainty exists in real-world practice about comparative effectiveness and safety outcomes.. To evaluate outcomes of different oral P2Y12 inhibitors in PCI patients.. We retrospectively studied patients treated between July 1, 2010, and December 31, 2013. Patients received clopidogrel, prasugrel, ticagrelor, or more than 1 antiplatelet (switch) during PCI. Outcomes were evaluated for major adverse cardiovascular events (MACE) and bleeding at 1 year. Propensity score matching with Cox proportional hazards analysis was used to determine predictors of MACE and bleeding.. A total of 8127 patients were included: clopidogrel (n = 6872), prasugrel (n = 605), ticagrelor (n = 181), and switch (n = 469). Treatment with prasugrel was associated with the lowest risk of MACE using multivariate regression (odds ratio [OR] = 0.57; 95% CI = 0.36-0.92; P = 0.02). In the propensity score-matched analysis, only the prasugrel group was associated with a lower risk of MACE compared with the clopidogrel group. Clopidogrel was associated with the lowest risk of major bleeding using multivariate regression (OR = 0.64; 95% CI = 0.42-0.98; P = 0.042). Both ticagrelor (hazard ratio [HR] = 2.00; 95% CI = 1.11-3.59) and the switch groups (HR = 1.65; 95% CI = 1.09-2.50) were associated with a greater risk of major bleeding compared with clopidogrel. However, no differences were found in the propensity score-matched analysis.. Dual antiplatelet therapies differed in both MACE and bleeds in a real-world setting of PCI. Prasugrel was associated with fewer MACE, whereas clopidogrel had fewer major bleeding events.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Delivery of Health Care, Integrated; Female; Hemorrhage; Humans; Male; Middle Aged; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Propensity Score; Proportional Hazards Models; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Retrospective Studies; Safety; Ticagrelor; Ticlopidine

Evaluation of antithrombotic treatments for acute coronary syndromes (ACS) requires balancing ischemic and bleeding risks to assess net benefit. We sought to compare the relative effects of ischemic and bleeding events on mortality.. In the PLATelet inhibition and patient Outcomes (PLATO) trial, we compared spontaneous ischemic events (myocardial infarction or stroke) with spontaneous major bleeding events (PLATO major, Thrombolysis In Myocardial Infarction [TIMI] major, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO] severe) with respect to risk of mortality using time-dependent Cox proportional hazards models. The comparison was performed using ratio of hazard ratios for mortality increase after ischemic vs bleeding events.. A total of 822 patients (4.4%) had ≥1 spontaneous ischemic event; 485 patients (2.6%), ≥1 spontaneous PLATO major bleed, 282 (1.5%), ≥1 spontaneous TIMI major bleed; and 207 (1.1%), ≥1 spontaneous severe GUSTO bleed. In patients who had both events, bleeding occurred first in most patients. Regardless of classification, major bleeding events were associated with increased short- and long-term mortality that were not significantly different from the increase associated with spontaneous ischemic events: ratio of hazard ratios (95% CIs) for short- and long-term mortality after spontaneous ischemic vs bleeding events: 1.46 (0.98-2.19) and 0.92 (0.52-1.62) (PLATO major); 1.26 (0.80-1.96) and 1.19 (0.58-2.24) (TIMI major), 0.72 (0.47-1.10) and 0.83 (0.38-1.79) (GUSTO severe) (all P>0.05) CONCLUSIONS: In patients with ACS on dual antiplatelet therapy, spontaneous major bleeding events seem "prognostically equivalent" to spontaneous ischemic complications. This result allows quantitative comparisons between both actual and predicted bleeding and ischemic risks. Our findings help to better define net clinical benefit of antithrombotic treatments and more accurately estimate mortality after ischemic and bleeding events in patients with ACS.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Risk Factors; Streptokinase; Stroke; Ticagrelor; Ticlopidine; Tissue Plasminogen Activator

The incorporation of the new antiplatelet agents (NAA) prasugrel and ticagrelor into routine clinical practice is irregular and data from the "real world" remain scarce. We aimed to assess the time trend of NAA use and the clinical safety and efficacy of these drugs compared with those of clopidogrel in a contemporary cohort of patients with acute coronary syndromes (ACS).. A multicenter retrospective observational study was conducted in patients with ACS admitted to coronary care units and prospectively included in the ARIAM-Andalusia registry between 2013 and 2015. In-hospital rates of major cardiovascular events and bleeding with NAA vs clopidogrel were analyzed using propensity score matching and multivariate regression models.. The study included 2906 patients: 55% received clopidogrel and 45% NAA. A total of 60% had ST-segment elevation ACS. Use of NAA significantly increased throughout the study. Patients receiving clopidogrel were older and were more likely to have comorbidities. Total mortality, ischemic stroke, and stent thrombosis were lower with NAA (2% vs 9%, P < .0001; 0.1% vs 0.5%, P = .025; 0.07% vs 0.5%, P = .025, respectively). There were no differences in the rate of total bleeding (3% vs 4%; P = NS). After propensity score matching, the mortality reduction with NAA persisted (OR, 0.37; 95%CI, 0.13 to 0.60; P < .0001) with no increase in total bleeding (OR, 1.07; 95%CI, 0.18 to 2.37; P = .094).. In a "real world" setting, NAA are selectively used in younger patients with less comorbidity and are associated with a reduction in major cardiac events, including mortality, without increasing bleeding compared with clopidogrel.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Coronary Care Units; Female; Hemorrhage; Humans; Male; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Propensity Score; Purinergic P2Y Receptor Antagonists; Registries; Retrospective Studies; Ticagrelor; Treatment Outcome

To determine clinically significant factors which may alter the effect of dual antiplatelet therapy with aspirin and ticagrelor or clopidogrel in patients who had undergone percutaneous coronary intervention and stent implantation.. The study included 378 patients. All the patients had undergone percutaneous coronary intervention and stent implantation. Platelet aggregation and genotyping for CYP2C19 *2 (rs4244285) and CYP4F2 (rs2108622, rs1558139, rs3093135 and rs2074902) was performed.. Significantly lower platelet aggregation values (%. Results of the current study showed that CYP4F2 rs3093135 TT variant carriers had a higher antiplatelet effect of ticagrelor, and more frequently had nonprocedural bleeding during ticagrelor therapy, as compared with AA and AT variant carriers.

Topics: Adenosine; Aged; Clopidogrel; Cytochrome P450 Family 4; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Pharmacogenomic Variants; Platelet Aggregation; Platelet Aggregation Inhibitors; Ticagrelor; Ticlopidine; Time Factors

To this day, there is no data concerning guideline adherence on P2Y12-inhibitors in Austria. Prasugrel and ticagrelor have been shown to be superior to clopidogrel in the treatment of acute coronary syndromes (ACS). However, recent data from European registries showed a reluctant prescription policy with rates of clopidogrel at discharge ranging from 35 to 55%.. In this prospective, multi-centre registry we assessed prescription rates of P2Y12-inhibitors in patients with ACS in four Austrian PCI centres. Parameters associated with the use of clopidogrel have been evaluated in multivariate logistic regression.. Between January and June 2015, 808 patients with ACS undergoing PCI were considered for further analysis. 416 (51.5%) presented with STEMI and 392 (48.5%) with NSTE-ACS. Mean age was 65.7 ± 12.4 and 240 (30.9%) were female. Twenty-eight (3.5%) died during the hospital stay. At discharge, 212 (27.2% of all patients) received clopidogrel, 260 (32.2%) prasugrel and 297 (36.8%) ticagrelor, while 11 (1.4%) did not receive any P2Y12-inhibitor. Of those patients, who were discharged with clopidogrel, 117 (55.2%) had no absolute contraindication against a more potent P2Y12-inhibitor. Diagnosis of NSTE-ACS (p<0.001), COPD (p = 0.049), and age (p<0.001) next to factors contributing to absolute contraindication were positively associated with the use of clopidogrel.. Despite a high level of care, a considerable number of patients were not treated with the more potent P2Y12-inhibitors. Parameters associated with a presumably higher risk of bleeding and side-effects against the more effective P2Y12 inhibitors were the most prominent factors for the prescription of clopidogrel.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aspirin; Austria; Clopidogrel; Female; Hemorrhage; Hospital Mortality; Humans; Male; Middle Aged; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prescription Drugs; Prospective Studies; Purinergic P2Y Receptor Antagonists; Registries; Ticagrelor; Ticlopidine

Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH).. An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population.. A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor.. Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.

Topics: Adenosine; Aged; Aspirin; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Purinergic P2Y Receptor Antagonists; Risk; Stroke; Ticagrelor; Treatment Outcome

According to the Italian National Report on drug use, thienopyridines (ticlopidine, clopidogrel and prasugrel) and ticagrelor represent the most prescribed antiplatelet agents, beside aspirin. The aim of this study was to analyse the safety profile of these drugs using data from spontaneous reporting of suspected adverse reactions (ADRs).. Suspected ADRs for ticlopidine, clopidogrel, prasugrel and ticagrelor, reported on the Italian National Pharmacovigilance Network between January 2009 and December 2016, were included in the analysis. All suspected ADRs were classified by frequency, seriousness, outcome, age and system organ class.. Clopidogrel showed the highest absolute number of suspected ADRs, followed by ticlopidine. However, these data need to be contextualized in view of the differences in marketing authorization dates, prescription rates and a characterization of the relative seriousness of ADRs per each drug. After the correction for prescription rate, ticagrelor showed the highest reporting trend and ticlopidine the lowest. Most ADRs occurred in the elderly, in particular for ticlopidine. Bleeding represents one of the most reported events (ticlopidine 40%, clopidogrel 26%, prasugrel 42%, ticagrelor 30%) and aspirin was the most frequently associated suspected drug. The majority of ADRs had complete recovery and were non-serious, except for ticlopidine (serious ADRs 53%). Prasugrel showed the highest percentage of 'life-threatening' events and 'death'.. Based on the analysis conducted on spontaneous ADRs reporting system in Italy, the safety profile of antiplatelet drugs seems favourable. However, the overall risk-benefit ratio of these drugs needs to be reassessed taking into account the appropriateness of use in particular populations at risk, such as the elderly. Based on this information, we believe that more attention from clinicians and/or an implementation of regulatory measures could be useful for clinical practice.

Topics: Adenosine; Adult; Aged; Aged, 80 and over; Aspirin; Female; Hemorrhage; Humans; Italy; Male; Middle Aged; Pharmacovigilance; Platelet Aggregation Inhibitors; Pyridines; Ticagrelor

We studied clinical outcomes and discontinuation rates in a 'real-world' population presenting with myocardial infarction treated with ticagrelor or clopidogrel.. Between January 2012 and May 2015, 992 patients with acute myocardial infarction undergoing invasive management and adequately pre-treated with dual antiplatelet therapy were prospectively enrolled. Platelet aggregation was measured using the Multiplate analyser. Baseline characteristics, in-hospital outcomes and 1-year outcomes were collected.. Patients treated with ticagrelor were younger and less likely to be diabetic, have a previous myocardial infarction or present with a ST-elevation myocardial infarction (all P < 0.05). Those treated with ticagrelor also had lower CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines; 20 ± 9.4 vs 23 ± 10.1, P < 0.0001) and GRACE (119 ± 28 vs 126 ± 32, P = 0.002) scores. High platelet reactivity was greatly reduced with ticagrelor compared to clopidogrel (16.1% vs 37.0%, respectively; P < 0.0001). Non-coronary artery bypass grafting-related thrombolysis in myocardial infarction major and minor bleeding occurred at similar rates in those treated with ticagrelor and clopidogrel. Rates of drug discontinuation in those treated with ticagrelor and clopidogrel were similar in hospital (20.2% vs 16.2%, P = 0.18) and between discharge and 1 year (29.9% vs 27.9%, P = 0.63). However, discontinuation due to dyspnoea, (3.3% vs 0%, P < 0.0001) and discontinuation due to any possible drug-related adverse event (9.3% vs 2.2%, P = 0.0001) was more common in those treated with ticagrelor compared to clopidogrel CONCLUSION: Ticagrelor is paradoxically being used in lower-risk patients rather than those most likely to benefit. Ticagrelor was associated with similar rates of bleeding but higher discontinuation rates due to adverse effects compared to clopidogrel.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Cohort Studies; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; Treatment Outcome; Withholding Treatment

Ticagrelor has become one of the first-line antiplatelet agents in acute coronary syndrome (ACS) patients recommend by the guideline due to its more potent and predictable antiplatelet effect. However, bleeding is still a severe drug adverse reaction of ticagrelor therapy. We report a first case on ticagrelor-induced life-threatening bleeding via the cyclosporine-mediated drug interaction.. A 58-year-old Chinese male who received cyclosporine 200 mg daily 5 years after renal transplantation. Ticagrelor was added for treating ACS. Unfortunately, gum bleeding and life-threatening bloody stool appeared 8 days later, accompanied with the sudden drop of blood pressure.. Ticagrelor was replaced with clopidogrel. Intravenous injection of proton pump inhibitor and agkistrodon snake venom hemocoagulase were used to stop the bleeding. Meanwhile, packed red blood cells and plasma were continuously transfused to maintain adequate blood volume.. The patient's bloody stool was well controlled after treatment.. The present case demonstrates that a potential drug-drug interaction (DDI) may lead to a life-threatening drug adverse reaction especially in special subjects. Therefore, regarding DDI, optimizing antiplatelet treatment should be considered for the efficacy and safety of P2Y12 receptor antagonist in this fragile population.

Topics: Adenosine; Cyclosporine; Drug Interactions; Hemorrhage; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Purinergic P2Y Receptor Antagonists; Ticagrelor

The performance of the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) and ACUITY (Acute Catheterization and Urgent Intervention Triage strategy) risk scores for the prediction of major bleeding in ticagrelor-treated acute coronary syndrome (ACS) patients who underwent percutaneous coronary intervention (PCI) is unknown. The aim of the present study is to validate the performance of both scores in a contemporary Chinese cohort of ACS patients hospitalized for PCI and administrated with ticagrelor. From January 2013 to December 2014, a total of 629 ticagrelor-treated ACS patients who underwent PCI were recruited consecutively. The overall rate of major bleeding defined by the BARC (Bleeding Academic Research Consortium) criteria was 1.7%. This incidence increased with the risk category of both the CRUSADE (very low, 0.6%; low, 1.3%; moderate, 1.1%; high, 7.0%; and very high, 13.0%;

Topics: Acute Coronary Syndrome; Adenosine; Aged; Area Under Curve; China; Decision Support Techniques; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prospective Studies; Purinergic P2Y Receptor Antagonists; Reproducibility of Results; Risk Assessment; Risk Factors; ROC Curve; Ticagrelor; Time Factors; Treatment Outcome

With this study, we sought to identify patient characteristics associated with clopidogrel prescription and its relationship with in-hospital adverse events in an unselected cohort of ACSs patients.. We studied all consecutive patients admitted at our institution for ACSs from 2012 to 2014. Patients were divided into two groups based on clopidogrel or novel P2Y12 inhibitors (prasugrel or ticagrelor) prescription and the relationship between clopidogrel use and patient clinical characteristics and in-hospital adverse events was evaluated using logistic regression analysis.. The population median age was 68 years (57-77 year) and clopidogrel was prescribed in 230 patients (46%). Patients characteristics associated with clopidogrel prescription were older age, female sex, non-ST-elevation ACS diagnosis, the presence of diabetes mellitus and anemia, worse renal and left ventricular functions and a higher Killip class. Patients on clopidogrel demonstrated a significantly higher incidence of in-hospital mortality (4.8%) than prasugrel and ticagrelor-treated patients (0.4%), while a nonstatistically significant trend emerged considering bleeding events. However, on multivariable logistic regression analysis female sex, the presence of anemia and Killip class were the only variables independently associated with in-hospital death.. Patients treated with clopidogrel showed a higher in-hospital mortality. However, clinical variables associated with its use identify a population at high risk for adverse events and this seems to play a major role for the higher in-hospital mortality observed in clopidogrel-treated patients.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aged, 80 and over; Chi-Square Distribution; Clopidogrel; Drug Prescriptions; Drug Therapy, Combination; Drug Utilization Review; Female; Hemorrhage; Hospital Mortality; Humans; Italy; Logistic Models; Male; Middle Aged; Multivariate Analysis; Non-ST Elevated Myocardial Infarction; Patient Selection; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Risk Factors; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Acute coronary syndrome (ACS) guidelines have been changed, favouring more potent antiplatelet drugs. We aimed to evaluate the safety and efficacy of a ticagrelor- instead of a clopidogrel-based primary dual antiplatelet (DAPT) regimen in ACS patients treated with newer-generation drug-eluting stents (DES).. CHANGE DAPT (clinicaltrials.gov: NCT03197298) assessed 2,062 consecutive real-world ACS patients, treated by percutaneous coronary intervention (PCI), the primary composite endpoint being net adverse clinical and cerebral events (NACCE: all-cause death, any myocardial infarction, stroke or major bleeding). In the clopidogrel (CP; December 2012-April 2014) and ticagrelor periods (TP; May 2014-August 2015), 1,009 and 1,053 patients were treated, respectively. TP patients were somewhat older, underwent fewer transfemoral procedures, and received fewer glycoprotein IIb/IIIa inhibitors. In the TP, the one-year NACCE rate was higher (5.1% vs. 7.8%; HR 1.53 [95% CI: 1.08-2.17]; p=0.02). Assessment of non-inferiority (pre-specified margin: 2.7%) was inconclusive (risk difference: 2.64 [95% CI: 0.52-4.77]; pnon-inferiority=0.48). TP patients had more major bleeding (1.2% vs. 2.7%; p=0.02) while there was no benefit in ischaemic endpoints. Propensity score-adjusted multivariate analysis confirmed higher NACCE (adj. HR 1.75 [95% CI: 1.20-2.55]; p=0.003) and major bleeding risks during TP (adj. HR 2.75 [95% CI: 1.34-5.61]; p=0.01).. In this observational study, the guideline-recommended ticagrelor-based primary DAPT regimen was associated with an increased event risk in consecutive ACS patients treated with newer-generation DES.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aged, 80 and over; Aspirin; Clopidogrel; Coronary Artery Disease; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Ticlopidine

A 54-year-old man underwent percutaneous coronary intervention (PCI) and two stents were placed on left anterior coronary artery and circumflex artery. Low molecular weight heparin (LMWH) together with ticagrelor 90 mg twice a day and acetylsalicylic acid (Aspirin) were started after PCI due to high risk of stent thrombosis. On the fourth day of patient's follow-up in the intensive care unit (ICU), bloody secretion was started from endotracheal tube. Hemoglobin dropping, bilateral infiltration on the chest X-ray and bleeding from lung were diagnosed as diffuse alveolar hemorrhage (DAH). Apart from LMWH and antiplatelet therapies with aspirin and ticagrelor, there were no other identified risk factors for DAH. As far as we know, our report is the first case of DAH caused by LMWH and dual anti-platelet therapy including ticagrelor.

Topics: Adenosine; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Drug Therapy, Combination; Fatal Outcome; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Pulmonary Alveoli; Purinergic P2Y Receptor Antagonists; Risk Factors; Stents; Thrombosis; Ticagrelor

Definition of the optimal duration of dual anti-platelet therapy (DAPT) is an important clinical issue, given the large number of patients having percutaneous coronary intervention (PCI), the costs and risks of pharmacologic therapy, the consequences of stent thrombosis, and the potential benefits of DAPT in preventing ischaemic outcomes beyond stent thrombosis. Nowadays, the rationale for a prolonged duration of DAPT should be not only the prevention of stent thrombosis, but also the prevention of ischaemic events unrelated to the coronary stenosis treated with index PCI. A higher predisposition to athero-thrombosis may persist for years after an acute myocardial infarction, and even stable patients with a history of prior myocardial infarction are at high risk for major adverse cardiovascular events. Recently, results of pre-specified post-hoc analyses of randomized clinical trials, including the PEGASUS-TIMI 54 trial, have shed light on strategies of DAPT in various clinical situations, and should impact the next rounds of international guidelines, and also routine practice. Accordingly, the 2015 to 2016 the Board of the Italian Society of Cardiology addressed newer recommendations on duration of DAPT based on most recent scientific information. The document states that physicians should decide duration of DAPT on an individual basis, taking into account ischaemic and bleeding risks of any given patient. Indeed, current controversy surrounding optimal duration of DAPT clearly reflects the fact that, nowadays, a one size fits all strategy cannot be reliably applied to patients treated with PCI. Indeed, patients usually have factors for both increased ischaemic and bleeding risks that must be carefully evaluated to assess the benefit/risk ratio of prolonged DAPT. Personalized management of DAPT must be seen as a dynamic prescription with regular re-evaluations of the risk/benefit to the patient according to changes in his/her clinical profile. Also, in order to derive more benefit than harm from new treatments, a multi-parametric approach using several risk scores of the ischaemic and bleeding risks might improve the process of risk factor characterization. In patients with high ischaemic risk, particularly those with a history of myocardial infarction, the benefits of extended DAPT (particularly with ticagrelor up to 3 years) are likely to outweigh the risks.

Topics: Adenosine; Aspirin; Cardiology; Drug Administration Schedule; Drug-Eluting Stents; Hemorrhage; Humans; Italy; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Societies, Medical; Thrombosis; Ticagrelor

The reasons for postdischarge adenosine diphosphate receptor inhibitor (ADPri) switching among patients with myocardial infarction (MI) are unclear. We sought to describe the incidence and patterns of postdischarge ADPri switching among patients with acute MI treated with percutaneous coronary intervention.. We used TRANSLATE-ACS (2010-2012) data to assess postdischarge ADPri switching among 8,672 MI patients discharged after percutaneous coronary intervention who remained on ADPri therapy 1 year post-MI. We examined patient-reported reasons for switching, GUSTO moderate or severe bleeding, major adverse cardiovascular events (MACEs), and definite stent thrombosis events around the time of the switch.. Among patients still on ADPri therapy 1 year post-MI, 663 (7.6%) switched ADPri during that year. Switching occurred at a median of 50 days postdischarge and most frequently in patients discharged on ticagrelor (64/226; 28.3%), followed by prasugrel (383/2,489; 15.4%) and clopidogrel (216/5,957; 3.6%) (P < .001). Among patients discharged on prasugrel, 97.3% of switches were to clopidogrel and 87.5% of ticagrelor switches were to clopidogrel; both of these groups most often cited cost as a reason for switching (43.6% and 39.1%, respectively), whereas 60.7% who switched from clopidogrel cited physician decision as a reason. In the 7 days preceding the switch from clopidogrel, 40 (18.5%) had a MACE and 12 (5.6%) had a definite stent thrombosis event, whereas that from prasugrel or ticagrelor, a GUSTO moderate or severe bleeding event occurred in 1 (0.3%) and 0 patients, respectively.. Postdischarge ADPri switching occurred infrequently within the first year post-MI and uncommonly was associated with MACEs or bleeding events.

Topics: Adenosine; Adenosine Diphosphate; Aged; Cardiovascular Diseases; Clopidogrel; Drug Substitution; Female; Hemorrhage; Humans; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Patient Discharge; Patient Preference; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P1 Receptor Antagonists; Ticagrelor; Ticlopidine

This study is a real world, observational study evaluating the treatment persistence of oral antiplatelet (OAP) therapy during a one-year follow-up in patients after an acute coronary syndrome (ACS).. Data on diagnosis, comorbidities, follow-up, OAP treatment, reasons, and decision maker for treatment discontinuation in patients who were discharged from a hospital in Belgium after an ACS between 1 July 2012 and 1 June 2013 were collected by cardiologists from 18 centres, up to 360 days from discharge. Out of the 671 patients surveyed, 295 patients were included in the persistence analysis. The remainder was excluded from the analysis due to the lack of precise information on OAP stopping date. The proportion of patients still using OAPs after 90, 180, 270, and 360 days was 92, 89, 83, and 73%, respectively. OAP persistence was higher for patients treated with prasugrel or ticagrelor. At 360 days, 79% of patients with a ST-segment elevation myocardial infarction (STEMI) and 66% of patients with a non-STEMI were still adhering to the prescribed course of treatment. Among the 79 patients with early treatment discontinuation, the mean treatment duration was 197.0 ± 125.18 days. The main decision taker in premature treatment cessation was the cardiologist (31% of cases), while the most frequently cited reasons included surgery (25%) and perceived high bleeding risk (19%).. Treatment persistence with OAPs after ACS in Belgium is high throughout the recommended period. Discontinuation was observed more often in patients treated with clopidogrel and was mainly initiated by the cardiologist.

Topics: Acute Coronary Syndrome; Administration, Oral; Aged; Belgium; Cardiologists; Clopidogrel; Drug Administration Schedule; Female; Hemorrhage; Humans; Male; Medication Adherence; Middle Aged; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Prasugrel Hydrochloride; Retrospective Studies; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

In 'real life' acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) and receiving contemporary antiplatelet treatment, data on dyspnea occurrence and impact on persistence with treatment are scarce. In a prospective, multicenter, cohort study, ACS patients undergoing PCI were recruited into the GReekAntiPlatElet (GRAPE) registry. During 1-year follow up, overall, 249/1989 (12.5%) patients reported dyspnea, more frequently at 1-month and decreasing thereafter. Multivariate analysis showed that ticagrelor administration (n = 738) at discharge was associated with the occurrence of dyspnea: Odds ratio 2.46 (95% confidence interval, CI, 1.87-3.25), p < 0.001. Older age, lower hematocrit, and prior bleeding event were also associated with dyspnea reports. Persistence, switching, and cessation rates were 68.3%, 20.9%, and 10.8% vs 76.7%, 12.5%, and 10.9% among patients reporting dyspnea compared with those who did not, p for trend = 0.002. In conclusion, in ACS patients undergoing PCI and treated with a P2Y

Topics: Acute Coronary Syndrome; Adenosine; Dyspnea; Female; Greece; Hematocrit; Hemorrhage; Humans; Male; Middle Aged; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Registries; Risk Factors; Ticagrelor; Ticlopidine

Management of ticagrelor-induced bleeding is challenging as platelet transfusion is ineffective. An effective strategy is needed. This study aimed to investigate. Blood was spiked with ticagrelor then supplemented by either HD or control. Several assays were performed: ADP-induced platelet aggregation measured by impedance aggregometry, light transmission and two global assays, thrombolastography with the platelet mapping device (TEG-PM) and a platelet-dependent thrombin generation assay (TGA).. Ticagrelor inhibited ADP-induced platelet aggregation and decreased the clot strength maximum amplitude (MA) in TEG-PM. Whereas none of the HDs corrected ticagrelor-induced platelet inhibition, rFVIIa shortened coagulation times, Fib increased clot firmness and FXIII decreased fibrinolysis. Consequently, they may bypass ticagrelor effects by acting on fibrin formation or fibrinolysis. Further studies are needed to confirm these data

Topics: Adenosine; Blood Coagulation; Blood Platelets; Dose-Response Relationship, Drug; Factor VIIa; Fibrinogen; Fibrinolysin; Hemorrhage; Hemostatics; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Recombinant Proteins; Thrombelastography; Ticagrelor; Time Factors; Tranexamic Acid

Triple antithrombotic therapy is used in patients who require systemic anticoagulation and undergo percutaneous coronary intervention (PCI) requiring dual antiplatelet therapy. Bleeding with this combination is significant; however, few studies have described outcomes with the use of newer oral P2Y. We aimed to compare outcomes among patients prescribed triple therapy with prasugrel or ticagrelor compared to triple therapy with clopidogrel in patients who underwent PCI and required warfarin.. We retrospectively evaluated 168 patients who received either prasugrel (n = 32) or ticagrelor (n = 10) and were matched (1:3) to those who received clopidogrel (n = 126) at the time of discharge from the index PCI visit. Matching was performed based on age ±10 years, sex, and indication for PCI. The primary outcome was the incidence of any bleeding during the 12-month follow-up. We also evaluated major adverse cardiovascular and cerebrovascular events (MACCEs).. Patient baseline characteristics were similar between groups. There was a significant excess of bleeding in patients who received prasugrel or ticagrelor compared to clopidogrel as part of triple therapy (28.6% vs 12.7%; odds ratio, 3.3; 95% confidence interval, 1.38-8.34). No differences were seen between groups in MACCEs.. The use of prasugrel or ticagrelor as part of triple antithrombotic therapy among patients who underwent PCI and received warfarin was associated with significantly more bleeding compared to patients who received clopidogrel. Therefore, higher potency P2Y

Topics: Adenosine; Aged; Aspirin; Cohort Studies; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Ticagrelor; Warfarin

Delivery of crushed ticagrelor via a nasogastric tube is a widely spread off-label use in unconscious patients following out-of-hospital cardiac arrest (OHCA). Notwithstanding the importance of a potent dual antiplatelet therapy in these patients, the efficacy of crushed ticagrelor after OHCA has not been established yet.. In a prospective, single-center, observational trial, 38 consecutive MI patients after OHCA were included. 27 patients (71.1 %) underwent mild induced hypothermia. The primary outcome was platelet inhibition at 24h measured by impedance aggregometry.. There was sufficient platelet inhibition in most patients after OHCA. In all hypothermic patients, there was an adequate platelet inhibition by ticagrelor at 24 h (p < 0.001). 15 patients (39.5 %) had significant gastroesophageal reflux and one patient with significant reflux had inadequate platelet inhibition at 24 h. There were no stent thrombosis or recurrent atherothrombotic events in these patients.. Administration of crushed ticagrelor via a nasogastric tube reliably inhibited platelet function in vitro and in vivo regardless of the presence of hypothermia in MI patients. Thus, platelet inhibition can be reliably achieved in MI patients during neuroprotective hypothermia following OHCA.

Topics: Adenosine; Administration, Oral; Adult; Aged; Aged, 80 and over; Female; Germany; Hemorrhage; Humans; Hypothermia, Induced; Intubation, Gastrointestinal; Male; Middle Aged; Out-of-Hospital Cardiac Arrest; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Ticagrelor; Time Factors; Treatment Outcome

The 30-day clinical outcomes with prasugrel or ticagrelor were compared using a US payer database in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).. Prasugrel and ticagrelor demonstrated superior efficacy with increased non-coronary artery bypass graft major bleeding compared with clopidogrel in randomized clinical trials. No direct randomized or observational studies have compared clinical outcomes between prasugrel and ticagrelor.. Patients hospitalized for ACS-PCI between August 1, 2011 and April 30, 2013 and prescribed prasugrel or ticagrelor were selected. Drug treatment cohorts were propensity matched based upon demographic and clinical characteristics. The primary objective compared 30-day net adverse clinical events (NACE) in prasugrel- and ticagrelor-treated patients using a prespecified 20% noninferiority margin. Secondary objectives included comparisons of major adverse cardiovascular events (MACE) and major bleeding.. Data were available for 16,098 patients (prasugrel, n = 13,134; ticagrelor, n = 2,964). In unmatched cohorts, prasugrel-treated patients were younger with fewer comorbidities than ticagrelor-treated patients, and 30-day NACE rates were 5.6 and 9.3%, respectively (P < 0.001). Following propensity matching, NACE was noninferior (P < 0.001) and 22% lower in prasugrel-treated than in ticagrelor-treated patients (RR, 0.78; 95% CI, 0.64-0.94). A 30-day adjusted MACE (RR, 0.80; 95% CI, 0.64-0.98) and major bleeding (RR, 0.65; 95% CI, 0.45-0.95) were also lower in prasugrel-treated patients compared with ticagrelor-treated patients.. In this "real-world," retrospective, observational study, physicians appear to preferentially use prasugrel in younger patients with lower risk of bleeding or comorbidities compared with ticagrelor. Following adjustment, clinical outcomes associated with prasugrel use appear as good, if not better, than those associated with ticagrelor in ACS-PCI patients. © 2015 Wiley Periodicals, Inc.

Topics: Acute Coronary Syndrome; Adenosine; Age Factors; Aged; Chi-Square Distribution; Comorbidity; Databases, Factual; Female; Hemorrhage; Hospitalization; Humans; Male; Middle Aged; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Prasugrel Hydrochloride; Propensity Score; Retrospective Studies; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; United States

To compare the clinical effects between individual antiplatelet therapy guided by CYP2C19 genetic testing and conventional dual antiplatelet therapy in patients with coronary artery disease after percutaneous coronary intervention.. In total of 628 coronary artery disease patients who had undergone successful percutaneous coronary intervention were included in this study. Patients were consecutively divided into routine group (n = 319) and individual group (n = 309) because of weather received CYP2C19 genetic testing. The individual group was divided again into extensive metabolizer group, intermediate metabolizer group, and poor metabolizer group according to CYP2C19 genotype. Then extensive metabolizer group received 75 mg daily of clopidogrel, intermediate metabolizer group received 150 mg daily of clopidogrel, and poor metabolizer group received ticagrelor 90 mg twice daily. Routine group was treated with clopidogrel 75 mg daily conventionally. The primary end points were defined as major adverse cardiovascular events (MACE), namely a composite of death from any cause, myocardial infarction, or target vessel revascularization. Safety end points were bleeding events classified by GUSTO.. All the 628 patients were followed for an average of 12 months and clinical outcomes were analyzed at 1, 6, and 12 months after discharge. The morbidity rates of MACE in individual group were all lower than those in routine group at 1, 6, and 12 months (1.3% vs. 5.6%, P = 0.003; 3.2% vs. 7.8%, P = 0.012; 4.2% vs. 9.4%, P = 0.010). No significant difference in the rates of bleeding was found between the 2 groups (P > 0.05). Even performed a multivariate logistic regression analysis, the benefit of individual antiplatelet therapy remained.. Individual antiplatelet therapy guided by CYP2C19 genetic testing significantly reduced the rate of MACE without an increase in the rate of bleeding in the near term in this Chinese population.

Topics: Adenosine; Aged; Aged, 80 and over; Asian People; Biotransformation; Chi-Square Distribution; China; Clopidogrel; Coronary Artery Disease; Cytochrome P-450 CYP2C19; Drug Monitoring; Female; Genotype; Hemorrhage; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Percutaneous Coronary Intervention; Pharmacogenomic Testing; Phenotype; Platelet Aggregation Inhibitors; Platelet Function Tests; Polymorphism, Genetic; Risk Factors; Ticagrelor; Ticlopidine; Treatment Outcome

Topics: Acute Coronary Syndrome; Adenosine; Aged; Arrhythmias, Cardiac; Clinical Trials as Topic; Drug Therapy, Combination; Dyspnea; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

Patients on dual antiplatelet therapy following percutaneous coronary intervention often have indications for concurrent oral anticoagulation or triple antithrombotic therapy (TT). Although TT may decrease ischemic complications, it may confer increased bleeding risk.. We hypothesize that the use of ticagrelor in TT is associated with higher risk of complications; accordingly, we sought to determine predictors of complications in patients on TT.. Patients discharged on TT after percutaneous coronary intervention were followed prospectively for 12 months. The primary endpoint was a composite of ischemic (death, myocardial infarction, stroke) and major bleeding complications or net adverse clinical event (NACE). A major secondary endpoint was BARC (Bleeding Academic Research Consortium) types 2, 3, or 5 bleeding. Outcomes were compared between ticagrelor- and clopidogrel-treated patients. Multivariable analyses were performed to elucidate predictors of complications.. Twenty-seven of 152 patients discharged on TT were on ticagrelor. NACE occurred in 52% of patients and BARC 2, 3, or 5 bleeding occurred in 18%. There was no difference in the primary or secondary outcome between ticagrelor vs clopidogrel subgroup. On logistic regressions, use of TT in patients with acute coronary syndrome (P = 0.002) and bridging in with ticagrelor (P = 0.02) were associated with increased NACE. Low estimated glomerular filtration rate was an independent predictor of bleeding (P = 0.03).. The risk of bleeding and ischemic complications among patients on TT is similar between those on ticagrelor and clopidogrel. However, caution with use of bridging anticoagulation should be taken when using ticagrelor.

Topics: Adenosine; Chi-Square Distribution; Clinical Trials as Topic; Clopidogrel; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Logistic Models; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Stroke; Ticagrelor; Ticlopidine; Treatment Outcome

The aim of this study was to evaluate access-site complications in patients with ST-segment elevation myocardial infarction treated with a transradial primary percutaneous coronary intervention relative to three different P2Y12 platelet inhibitors.. We enrolled 334 consecutive patients (76.9% men, age: 59.4±9.1 years) treated by one of the following: clopidogrel (n=118), prasugrel (n=102), and ticagrelor (n=114). The use of the IIb/IIIa inhibitor, abciximab, was left to the operators' discretion. The time needed to achieve patent hemostasis, compression time, and local complications were analyzed.. The baseline characteristics were similar in all three P2Y12 platelet inhibitor groups. Abciximab was used in 72 (21.6%) patients. Administration of abciximab was associated with a higher incidence of grade II and III hematomas (23.6 vs. 5.0%, P<0.0001, and 5.6 vs. 1.1%, P=0.041, respectively). Among different platelet P2Y12 receptor inhibitor groups, the incidences of hematomas grade II and III were similar in patients who did (P≥0.14) and did not (P≥0.31) receive abciximab. There were no grade IV or V hematomas in any of the groups. Patent hemostasis was achieved faster (24.5±13.4 vs. 43.5±30.0 min, P<0.0001) and compression time was shorter (113.2±53.6 vs. 217.8±115.5 min, P<0.0001) when abciximab was not used. Radial artery occlusion occurred in one (0.3%) patient.. After transradial primary percutaneous coronary intervention, early patent hemostasis and short artery compression times were associated with a higher incidence of local hematomas. The incidence of hematomas was dependent on the use of abciximab, but unrelated to the type of P2Y12 inhibitor used. All hematomas were without clinical consequences.

Topics: Abciximab; Adenosine; Aged; Antibodies, Monoclonal; Catheterization, Peripheral; Clopidogrel; Female; Hematoma; Hemorrhage; Hemostatic Techniques; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Punctures; Purinergic P2Y Receptor Antagonists; Radial Artery; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Guidelines recommend prasugrel or ticagrelor instead of clopidogrel in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary interventions (PCI).. We sought to describe the trends in uptake of the newer agents and analyse the clinical characteristics and short-term outcomes of patients treated with clopidogrel, prasugrel or ticagrelor.. We analysed the temporal trends of antiplatelet use since the availability of prasugrel (2009-2013) in patients with ACS from the Melbourne Interventional Group registry. To assess clinical characteristics and outcomes, we included 1850 patients from 2012 to 2013, corresponding to the time all three agents were available. The primary outcome was major adverse cardiovascular events (MACE). The safety end-point was in-hospital bleeding.. For the period of 2009-2013, the majority of patients were treated with clopidogrel (72%) compared with prasugrel (14%) or ticagrelor (14%). There was a clear trend towards ticagrelor by the end of 2013. Patients treated with clopidogrel were more likely to present with non-ST-elevation ACS, be older, and have more comorbidities. There was no difference in unadjusted 30-day mortality (0.9 vs 0.5 vs 1.0%, P = 0.76), myocardial infarction (2 vs 1 vs 2%, P = 0.52) or MACE (3 vs 3 vs 4%, P = 0.57) between the three agents. There was no difference in in-hospital bleeding (3 vs 2 vs 2%, P = 0.64).. Prasugrel and ticagrelor are increasingly used in ACS patients treated with PCI, predominantly in a younger cohort with less comorbidity. Although antiplatelet therapy should still be individualised based on the thrombotic and bleeding risk, our study highlights the safety of the new P2Y12 inhibitors in contemporary Australian practice.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aged, 80 and over; Australia; Clopidogrel; Comorbidity; Female; Hemorrhage; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Registries; Ticagrelor; Ticlopidine; Treatment Outcome

Secondary prevention in myocardial infarction patients is paramount to prevent recurrences. Dual antiplatelet therapy has been shown to reduce the risk of subsequent events up to 1 year and beyond in the PEGASUS-TIMI 54 trial. This study aimed to estimate the annual number of myocardial infarction patients with PEGASUS characteristics in Spain and to analyze short- and long-term outcomes in these patients.. The number of myocardial infarction patients was estimated assuming a Poisson distribution. Myocardial infarction incidence and mortality rates obtained from population registries (IBERICA and REGICOR) were properly adjusted. The proportion of myocardial infarction patients with PEGASUS characteristics was estimated with a REGICOR cohort of consecutive patients from 2003-2009 (n=1391). This cohort follow-up was used to compare the occurrence of reinfarction and death at 1 year and at the end of the follow-up (4.7 years) in patients with and without PEGASUS characteristics by Cox regression.. The estimated annual number of stable myocardial infarction patients aged ≥ 50 years and without bleeding events was 41 311. Of these, 22 493 had at least 1 PEGASUS characteristic (diabetes, previous myocardial infarction, or chronic kidney disease). At 4.7 years of follow-up, having any PEGASUS characteristic or age ≥ 65 years was associated with a higher risk of cardiovascular and all-cause death in adjusted analyses (hazard ratio=3.44 and 2.21, 95% confidence interval, 1.22-9.74 and 1.11-4.42, respectively).. In Spain, more than 50% of the stable myocardial infarction patients aged ≥ 50 years are estimated to have at least 1 PEGASUS characteristic, which substantially increases the long-term risk of cardiovascular and all-cause death.

Topics: Adenosine; Age Factors; Aged; Aged, 80 and over; Aspirin; Diabetes Mellitus; Drug Therapy, Combination; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Patient Selection; Platelet Aggregation Inhibitors; Prevalence; Prognosis; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Assessment; Secondary Prevention; Spain; Ticagrelor; Time Factors

Although ticagrelor has been well-known to improve clinical outcomes in patients with acute myocardial infarction (AMI) without increased bleeding risk, its clinical impacts have not been well established in East Asian patients.. Between November 2011 and June 2015, a total of 8010 patients (1377 patients were prescribed ticagrelor and 6633 patients clopidogrel) undergoing successful revascularization were analyzed from Korea Acute Myocardial Infarction Registry-National Institute of Health. The patients who discontinued or occurred in-hospital switching between two antiplatelet agents were excluded.. After propensity score matching (1377 pairs), no difference in the composite of cardiac death, MI, stroke, or target vessel revascularization at 6months was observed between two groups (4.2% vs. 4.9%, p=0.499). However, the incidences of in-hospital Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding were higher in ticagrelor than clopidogrel (2.6% vs. 1.2%, p=0.008; 3.8% vs. 2.5%, p=0.051). The in-hospital mortality was higher in patients with than those without TIMI major bleeding (11.3% vs. 0.9%, p<0.001). In a subgroup analysis, a higher risk for in-hospital TIMI major bleeding with ticagrelor was observed in patients≥75years or with body weight<60kg (odd ratio [OR]=3.209; 95% confidence interval [CI]=1.356-7.592) and in those received trans-femoral intervention (OR=1.996; 95% CI=1.061-3.754).. Our study shows that ticagrelor did not reduce ischemic events yet, however, was associated with increased risk of bleeding complications compared with clopidogrel. Further large-scale, long-term, randomized trials should be required to assess the outcomes of ticagrelor for East Asian patients with AMI.

Topics: Adenosine; Clopidogrel; Female; Hemorrhage; Hospitalization; Humans; Male; Myocardial Infarction; Percutaneous Coronary Intervention; Propensity Score; Registries; Republic of Korea; Ticagrelor; Ticlopidine; Treatment Outcome

PEGASUS trial reported reduction of composite primary endpoint after conventional 180mg/daily ticagrelor (CT), and lower 120mg/daily dose ticagrelor (LT) at expense of extra bleeding. Following approval of CT and LT for long-term secondary prevention indication, recent FDA review verified some bleeding outcomes in PEGASUS. To compare the risks after CT and LT against placebo by seven TIMI scale variables, and 9 bleeding categories considered as serious adverse events (SAE) in light of PEGASUS drug discontinuation rates (DDR). The DDR in all PEGASUS arms was high reaching astronomical 32% for CT. The distribution of some outcomes (TIMI major, trauma, epistaxis, iron deficiency, hemoptysis, and anemia) was reasonable. However, the TIMI minor events were heavily underreported when compared to similar trials. Other bleedings (intracranial, spontaneous, hematuria, and gastrointestinal) appear sporadic, lacking expected dose-dependent impact of CT and LT. Few SAE outcomes (fatal, ecchymosis, hematoma, bruises, bleeding) paradoxically reported more bleeding after LT than after CT. Many bleeding outcomes were probably missed in PEGASUS potentially due to massive non-compliance, information censoring, or both. The FDA must improve reporting of trial outcomes especially in the sponsor-controlled environment when DDR and incomplete follow-up rates are high.

Topics: Adenosine; Censorship, Research; Drug Administration Schedule; Hemorrhage; Humans; Myocardial Infarction; Randomized Controlled Trials as Topic; Ticagrelor

Topics: Adenosine; Aged; Female; Fibrinolytic Agents; Hemorrhage; Humans; Stroke; Thrombolytic Therapy; Ticagrelor; Tissue Plasminogen Activator

 To estimate the potential magnitude in unselected patients of the benefits and harms of prolonged dual antiplatelet therapy after acute myocardial infarction seen in selected patients with high risk characteristics in trials..  Observational population based cohort study..  PEGASUS-TIMI-54 trial population and CALIBER (ClinicAl research using LInked Bespoke studies and Electronic health Records)..  7238 patients who survived a year or more after acute myocardial infarction..  Prolonged dual antiplatelet therapy after acute myocardial infarction..  Recurrent acute myocardial infarction, stroke, or fatal cardiovascular disease. Fatal, severe, or intracranial bleeding..  1676/7238 (23.1%) patients met trial inclusion and exclusion criteria ("target" population). Compared with the placebo arm in the trial population, in the target population the median age was 12 years higher, there were more women (48.6% v 24.3%), and there was a substantially higher cumulative three year risk of both the primary (benefit) trial endpoint of recurrent acute myocardial infarction, stroke, or fatal cardiovascular disease (18.8% (95% confidence interval 16.3% to 21.8%) v 9.04%) and the primary (harm) endpoint of fatal, severe, or intracranial bleeding (3.0% (2.0% to 4.4%) v 1.26% (TIMI major bleeding)). Application of intention to treat relative risks from the trial (ticagrelor 60 mg daily arm) to CALIBER's target population showed an estimated 101 (95% confidence interval 87 to 117) ischaemic events prevented per 10 000 treated per year and an estimated 75 (50 to 110) excess fatal, severe, or intracranial bleeds caused per 10 000 patients treated per year. Generalisation from CALIBER's target subgroup to all 7238 real world patients who were stable at least one year after acute myocardial infarction showed similar three year risks of ischaemic events (17.2%, 16.0% to 18.5%), with an estimated 92 (86 to 99) events prevented per 10 000 patients treated per year, and similar three year risks of bleeding events (2.3%, 1.8% to 2.9%), with an estimated 58 (45 to 73) events caused per 10 000 patients treated per year..  This novel use of primary-secondary care linked electronic health records allows characterisation of "healthy trial participant" effects and confirms the potential absolute benefits and harms of dual antiplatelet therapy in representative patients a year or more after acute myocardial infarction.

Topics: Adenosine; Aged; Aged, 80 and over; Aspirin; Cardiovascular Diseases; Cause of Death; Clinical Trials as Topic; Cohort Studies; Coronary Disease; Drug Therapy, Combination; Electronic Health Records; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Risk Factors; Secondary Prevention; Stroke; Ticagrelor; Time Factors

The American Urological Association (AUA) guidelines state that continuing anticoagulation and antiplatelet agents in routine ureteroscopy (URS) is safe and without increased risk of complications. However, these recommendations are based on small case series; thus, we sought to analyze bleeding-related complications among patients on antiplatelet therapy (APT).. Overall, 4799 URS procedures performed at our institution between June 2009 and February 2016 were identified. Records were then retrospectively reviewed to confirm APT use and to identify periprocedural complications. Antiplatelet agents evaluated included aspirin (low dose and full dose) and P2Y12 receptor antagonists (clopidogrel, prasugugrel, ticagrelor). Patients were excluded if they were taking a concurrent anticoagulant agent or if additional non-URS procedures were performed.. Of 4799 URS procedures, 314 (6.5%) were performed on patients taking APT, of which 234 (74.5%) held APT, 63 (20.1%) continued APT, and 17 (5.4%) continued dual APT. The mean age was 70.1 years, and the majority of patients (69.6%) underwent a stone procedure with a stone-free rate of 80.2%. The overall bleeding-related complication rate was 1.9%, whereas the significant bleeding-related event rate was 1.6% and this did not differ among the groups (p = 0.3). The power to detect a 3% difference in bleeding between the groups was 0.95.. Continuing APT in patients on chronic therapy does not appear to pose an increased risk of bleeding-related complications. Our findings support the current AUA guidelines as they relate to APT.

Topics: Adenosine; Adult; Aged; Anticoagulants; Aspirin; Blood Platelets; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Risk; Ticagrelor; Ticlopidine; Ureteroscopy

Pre-hospital ticagrelor, given less than 1h before coronary intervention (PCI), failed to improve coronary reperfusion in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary PCI. It is unknown whether a longer interval from ticagrelor administration to primary PCI might reveal any improvement of coronary reperfusion.. We retrospectively compared 143 patients, pre-treated in spoke centers or ambulance with ticagrelor at least 1.5h before PCI (Pre-treatment Group), with 143 propensity score-matched controls treated with ticagrelor in the hub before primary PCI (Control Group) extracted from RENOVAMI, a large observational Italian registry of more than 1400 STEMI patients enrolled from Jan. 2012 to Oct. 2015 (ClinicalTrials.gov id: NCT01347580). The median time from ticagrelor administration and PCI was 2.08h (95% CI 1.66-2.84) in the Pre-treatment Group and 0.56h (95% CI 0.33-0.76) in the Control Group. TIMI flow grade before primary PCI in the infarct related artery was the primary endpoint.. The primary endpoint, baseline TIMI flow grade, was significantly higher in Pre-treatment Group (0.88±1.14 vs 0.53±0.86, P=0.02). However in-hospital mortality, in-hospital stent thrombosis, bleeding rates and other clinical and angiographic outcomes were similar in the two groups.. In a real world STEMI network, pre-treatment with ticagrelor in spoke hospitals or in ambulance loading at least 1.5h before primary PCI is safe and might improve pre-PCI coronary reperfusion, in comparison with ticagrelor administration immediately before PCI.

Topics: Adenosine; Aged; Ambulances; Chi-Square Distribution; Coronary Angiography; Coronary Thrombosis; Electrocardiography; Emergency Medical Services; Female; Hemorrhage; Hospital Mortality; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Propensity Score; Proportional Hazards Models; Registries; Retrospective Studies; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Stents; Ticagrelor; Time Factors; Time-to-Treatment; Transportation of Patients; Treatment Outcome

Topics: Adenosine; Clinical Decision-Making; Drug Approval; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Recurrence; Risk Assessment; Risk Factors; Secondary Prevention; Ticagrelor; Time Factors; Treatment Outcome; United States; United States Food and Drug Administration

Contemporary use of dual antiplatelet therapy and consistency with guideline recommendations in acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI) have not been well characterized.. The COAPT was a prospective, observational, multicenter, longitudinal study of patients with myocardial infarction (MI) undergoing PCI. Baseline characteristics, treatment patterns, processes of care, factors associated with switching to and from novel adenosine diphosphate receptor inhibitors (ADPris), and in-hospital outcomes are described.. Among 2,179 MI patients undergoing PCI during their index hospitalization, 1,328 (60.9%) had ST elevation. Initial ADPri use included clopidogrel in 1,812 (83.2%), prasugrel in 125 (5.7%), and ticagrelor in 242 (11.1%). At discharge, 1,597 patients (73.4%) were prescribed clopidogrel, 220 (10.1%) prasugrel, and 358 (16.5%) ticagrelor. Switching between ADPri therapies during the index hospitalization occurred in 15.3%, 22.4%, and 25.2% of patients initially started on clopidogrel, prasugrel, and ticagrelor, respectively. Most switches over the 15-month study period occurred during the index admission (16.8% of patients vs 4.4% switches postdischarge). Major adverse cardiovascular events occurred in 7.5% of patients during the index hospitalization. In-hospital bleeding events occurred in 6.0% of patients and most were mild.. Despite randomized trial evidence and guideline recommendations, only a minority of Canadian MI patients undergoing PCI initially received or were discharged on one of the newer ADPri agents. These findings suggest an opportunity to improve upon the appropriate selection of the ADPris at index hospitalization and discharge in Canadian MI patients undergoing PCI.

Topics: Adenosine; Adult; Aged; Aged, 80 and over; Canada; Clopidogrel; Drug Substitution; Emergency Medical Services; Emergency Service, Hospital; Female; Hemorrhage; Hospitalization; Humans; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Ticlopidine; Young Adult

Topics: Adenosine; Aged; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Percutaneous Coronary Intervention; Purinergic P2Y Receptor Antagonists; Ticagrelor

Treatment with warfarin in combination with clopidogrel has been shown to reduce the incidence of major bleeding as compared to triple antithrombotic therapy (TT; warfarin, clopidogrel and aspirin). However, there are uncertainties regarding the risk for thrombosis since poor-responsiveness to clopidogrel is common. Ticagrelor is a more potent platelet inhibitor, but data supporting concurrent use of ticagrelor and warfarin (dual antithrombotic therapy, DT) is limited. This study therefore sought to evaluate the risk of bleeding and thrombosis associated with DT after an acute coronary syndrome (ACS).. We identified all ACS patients on DT upon discharge from Helsingborg Hospital and Skåne University Hospital in Malmö and Lund, Sweden, during 2013. Patients on DT were compared with historical controls discharged with TT. Major bleeding was defined in accordance with the HAS-BLED derivation study. Patients were retrospectively followed for three months.. In total, 107 DT patients were identified and compared with 159 controls on TT. Mean HAS-BLED bleeding risk score and duration of treatment were similar between the groups (HAS-BLED 2.2+/-0.8 vs 2.2+/-1.0 units, p=NS; duration 2.7+/-0.8 vs 2.5+/-0.9months, p=NS; DT vs TT). The incidence of spontaneous major bleeding was similar between the groups, as was a composite of all thrombotic events, i.e. peripheral embolism, stroke/TIA and acute coronary syndrome (bleeding 8/106 (7.5%) vs 11/157 (7.0%), p=NS; thrombosis 5/106 (4.7%) vs 5/157 (3.2%), p=NS; DT vs TT).. Rates of thrombotic and bleeding events were similar in patients with TT and patients with ticagrelor and warfarin.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aged, 80 and over; Aspirin; Atrial Fibrillation; Clopidogrel; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Thrombosis; Ticagrelor; Ticlopidine; Treatment Outcome; Warfarin

Ticagrelor is a direct-acting reversibly binding P2Y12 antagonist and is widely used as an antiplatelet therapy for the prevention of cardiovascular events in acute coronary syndrome patients. However, antiplatelet therapy can be associated with an increased risk of bleeding. Here, we present data on the identification and the in vitro and in vivo pharmacology of an antigen-binding fragment (Fab) antidote for ticagrelor. The Fab has a 20 pM affinity for ticagrelor, which is 100 times stronger than ticagrelor's affinity for its target, P2Y12. Despite ticagrelor's structural similarities to adenosine, the Fab is highly specific and does not bind to adenosine, adenosine triphosphate, adenosine 5'-diphosphate, or structurally related drugs. The antidote concentration-dependently neutralized the free fraction of ticagrelor and reversed its antiplatelet activity both in vitro in human platelet-rich plasma and in vivo in mice. Lastly, the antidote proved effective in normalizing ticagrelor-dependent bleeding in a mouse model of acute surgery. This specific antidote for ticagrelor may prove valuable as an agent for patients who require emergency procedures.

Topics: Adenosine; Animals; Antibodies; Antibodies, Neutralizing; Antibody Specificity; Antidotes; Broadly Neutralizing Antibodies; CHO Cells; Cricetinae; Cricetulus; Crystallography, X-Ray; Hemorrhage; Humans; Immunoglobulin Fab Fragments; Mice; Models, Molecular; Platelet Aggregation; Protein Engineering; Ticagrelor

ADP-induced platelet activation via P2Y12 receptor plays a pivotal role in the pathophysiology of arterial thrombosis and acute coronary syndrome. The value of dual antiplatelet therapy with the addition of the thienopyridine clopidogrel to aspirin has been widely established. Prasugrel, another thienopyridine, has demonstrated more potent platelet inhibition and efficacy than clopidogrel, although this drug requires metabolic activation and is associated with increased risk of bleedings.. In this article, we discuss the role of ticagrelor in the management of non-ST elevation acute coronary syndromes treatment. We describe the unique pharmacokinetic and pharmacodynamic properties of this drug and the extensive data obtained by preclinical and Phase II and III clinical studies.. Current guidelines recommend ticagrelor, in addition to aspirin, for patients with non-ST-segment elevation acute coronary syndromes at moderate to high-risk regardless of initial therapeutic strategy. Benefit of ticagrelor, as regard mortality, may be related to off-target effects of the drug, especially those involving the metabolism of adenosine. Ticagrelor represents a cost-effective alternative in the spectrum of P2Y12 inhibitors; however, further studies are required to enable the physician to choose the most appropriate antiplatelet agent for each patient.

Topics: Acute Coronary Syndrome; Adenosine; Animals; Aspirin; Drug Therapy, Combination; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Purinergic P2Y Receptor Antagonists; Ticagrelor

To compare healthcare resource utilization (HCRU) and healthcare costs in patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with prasugrel or ticagrelor.. Hospital charge master data were used to identify ACS-PCI patients aged ≥ 18 years with ≥ 1 in-hospital claim for prasugrel or ticagrelor between August 1, 2011-April 30, 2013. Treatment groups were propensity matched for baseline and index hospitalization characteristics. HCRU and costs were assessed through 90-days post-discharge. Costs were determined based on hospital-specific cost-to-charge ratios and adjusted to 2013 US dollars.. Before matching, ticagrelor patients were older, more-often female, and had increased cardiovascular (CV) and bleeding risks compared with prasugrel patients. Propensity-matched length of index hospital stay (4.7 vs 4.9 days, p = 0.23) and risk for all-cause [30-day: relative risk (RR) = 0.86; 95% CI = 0.73-1.0; 90-day: RR = 0.90; 95% CI = 0.80-1.0, and CV-related (30-day: RR = 0.77; 95% CI = 0.59-1.0; 90-day: RR = 0.89; 95% CI = 0.73-1.1) re-hospitalizations did not significantly differ between prasugrel and ticagrelor, respectively. Compared to ticagrelor, the propensity-matched risk of re-hospitalization for myocardial infarction (MI) (30-day: RR = 0.39; 95% CI = 0.21-0.75; 90-day: RR = 0.53; 95% CI = 0.34-0.81) and an outpatient medical encounter for dyspnea (30-day: RR = 0.49; 95% CI = 0.33-0.74; 90-day: RR = 0.60; 95% CI = 0.46-0.80) were significantly lower for prasugrel patients, with no significant differences in bleeding encounters between groups (30-day: RR =  0.87; 95% CI = 0.54-1.40; 90-day: RR = 1.0; 95% CI = 0.71-1.50). Matched total healthcare costs were not significantly different between groups during the index hospitalization ($36,011 vs $37,247, p = 0.21), 30-days post-discharge ($2007 vs $2522, p = 0.48), 90-days post-discharge ($4564 vs $5242, p = 0.49), and aggregate of the index hospitalization through 90-day follow-up ($40,576 vs $42,494, p = 0.09) timeframes.. Re-hospitalization for MI and outpatient encounters for dyspnea were lower in prasugrel treated than in ticagrelor treated ACS-PCI patients up to 90-days post-index hospitalization discharge, with no difference in bleeding encounters or healthcare costs between the two populations. This data supports the utility of prasugrel in routine clinical practice. These findings should be considered within limitations of observational research.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Dyspnea; Female; Health Services; Hemorrhage; Humans; Length of Stay; Male; Middle Aged; Patient Readmission; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Propensity Score; Ticagrelor

After the successful PLATO, failed both PHILO and ATLANTIC, PEGASUS trial assessed efficacy and safety of ticagrelor (120 mg/day and 180 mg/day) on top of aspirin versus aspirin alone beyond 1 year in patients with stable coronary disease. Similar to PLATO, PEGASUS revealed reduction of composite primary endpoint after ticagrelor at expense of extra bleeding. However, there were major fundamental differences between the trial outcomes. Hence, the shift of evidence with ticagrelor from PLATO to PEGASUS trials has been comprehended. In contrast to PLATO, in PEGASUS there were more premature permanent ticagrelor discontinuations (PPTD): RR=1.35; 95%CI 1.29-1.42, p<0.0001; significant excess of cancer deaths (RR=1.46; 95%CI 1.02-2.06,p=0.034), trend to more sepsis deaths (RR=1.29; 95%CI 0.76-2.20), and most importantly identical all-cause mortality (RR=1.00; 95%CI 0.86-1.16, p=0.99) versus placebo. Applied conservative TIMI bleeding classification in PEGASUS did not correspond with PPTD rate, with potential heavy underreporting of hemorrhagic events. Finally, unexplained late addition of 198 primary events in PEGASUS is concerning. PEGASUS failed to confirm ticagrelor mortality benefit reported in PLATO, but rather discover additional shortcomings.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Clopidogrel; Follow-Up Studies; Hemorrhage; Humans; Mortality; Neoplasms; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Sepsis; Ticagrelor; Ticlopidine

Newer P2Y12 inhibitors, such as prasugrel and ticagrelor, have greater antiplatelet efficacy but may increase the risk of bleeding. In this study, we compared the pharmacodynamic efficacy of prasugrel and ticagrelor in East Asian patients with acute coronary syndrome (ACS).. We selected 83 ACS patients undergoing percutaneous coronary intervention who were discharged with 90 mg ticagrelor twice daily (n = 24), 10 mg prasugrel daily (n = 39) or 5 mg prasugrel daily (n = 20). After 2 to 4 weeks, on-treatment platelet reactivity (OPR) was assessed in terms of P2Y12 reaction units (PRUs) using the VerifyNow P2Y12 assay (Accumetrics). We compared East Asian (85 < PRU ≤ 275) and Caucasian (85 < PRU ≤ 208) criteria for assessing the therapeutic window of OPR.. OPR was lowest in the ticagrelor group, followed by the 10 mg prasugrel and 5 mg prasugrel groups (49.1 ± 29.9 vs. 83.7 ± 57.1 vs. 168.5 ± 60.8, respectively; p < 0.001). The 5 mg prasugrel group had the highest proportion of patients with OPR values within the therapeutic window, followed by the 10 mg prasugrel and ticagrelor groups (90.0% vs. 46.2% vs. 12.5%, respectively; p < 0.001 for East Asian criteria; 60.0% vs. 43.6% vs. 12.5%, respectively; p < 0.001 for Caucasian criteria).. Short-term administration of 5 mg prasugrel facilitated maintenance within the therapeutic window of OPR compared with the 10 mg prasugrel and ticagrelor groups. Thus, 5 mg prasugrel daily may be the optimal antiplatelet regimen for stabilized East Asian ACS patients.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Asian People; Blood Platelets; Drug Administration Schedule; Drug Monitoring; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Pilot Projects; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Republic of Korea; Retrospective Studies; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; White People

Our objective was to compare 1-year real-world healthcare resource utilization (HRU), associated charges, and antiplatelet treatment patterns among patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with ticagrelor or prasugrel.. Using the ProMetis-Lx database, adult ACS-PCI patients treated with ticagrelor or prasugrel post-discharge were identified between 1 August 2011 and 31 May 2013 and propensity matched to adjust for baseline differences.. Before matching, ticagrelor-treated patients (n = 2991) were older with increased baseline ischemic and bleeding risks compared with prasugrel-treated patients (n = 12,797). After matching, ticagrelor patients had higher all-cause HRU (2.5 vs. 2.4 per patient per month; P = 0.012) and cardiovascular (CV) HRU (0.4 vs. 0.3 per patient per month; P = 0.026), with the difference in CV rehospitalizations (17.7 vs. 15.7 %; P = 0.011) primarily driven by congestive heart failure (CHF) (4.9 vs. 3.8 %; P = 0.02). All-cause charges within 1 year did not significantly differ between groups ($US5456 vs. 4844 per patient per month; P = 0.37), but dyspnea-related total charges were significantly higher with ticagrelor ($US139 vs. 95 per patient per month; P = 0.005). Although infrequent, switching was slightly higher with ticagrelor (8.3 vs. 6.0 %; P < 0.001) at 1 year, and mean persistence was slightly longer with prasugrel (150 vs. 159 days; P = 0.002), with no significant difference in mean adherence (61 vs. 63 %; P = 0.17).. Overall monthly HRU was slightly lower with prasugrel than with ticagrelor, with no significant difference in bleeding HRU. Prasugrel was associated with slightly higher pharmacy charges, but lower dyspnea charges, resulting in no significant difference in total charges. Patients receiving prasugrel tended to use it for longer than those receiving ticagrelor as less switching occurred. These findings may aid decision making, but must be tempered due to inherent study limitations.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Anticoagulants; Comorbidity; Female; Health Services; Hemorrhage; Humans; Male; Middle Aged; Patient Readmission; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Retrospective Studies; Ticagrelor

A 55-year-old man presented with acute ST-elevation myocardial infarction. He received rescue angioplasty with one drug eluting stent. He developed marked breathlessness and haemoptysis two days later. Investigations led to the diagnosis of pulmonary haemorrhage, possibly from pneumonitis caused by ticagrelor. He was successfully managed with high-dose steroids and ticagrelor was replaced with clopidogrel. On stopping the steroids a month later, mild haemoptysis recurred and this was managed conservatively. Pneumonitis and pulmonary haemorrhage is rarely reported with acute myocardial infarction, but poses serious challenge to the patient and the clinician. Diagnosis may be delayed as breathlessness can occur due to myriad causes after myocardial infarction. Interrupting dual anti-platelet therapy after angioplasty could lead to devastating stent thrombosis.

Topics: Adenosine; Angioplasty; Hemoptysis; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Pneumonia; Purinergic P2Y Receptor Antagonists; Radiography, Thoracic; Thrombosis; Ticagrelor

Topics: Adenosine; Aged; Aspirin; Cohort Studies; Dyspnea; Female; Hemorrhage; Humans; Male; Medication Adherence; Myocardial Infarction; Patient Satisfaction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Ticagrelor

Ticagrelor (Brilique®) is a novel reversible platelet inhibitor at P2Y12 receptor used in patients with acute coronary syndrome and patients undergoing percutaneous coronary interventions. Unlike clopidogrel (Plavix®), ticagrelor has a quicker offset of action, and therefore, it seems that platelet function recovers faster on discontinuation of therapy. These drugs sometimes cannot be stopped before coronary artery bypass grafting due to the risk of stent thrombosis or in case of emergency operations. Therefore, we investigated whether the continued preoperative use of ticagrelor influences the perioperative course of cardiac surgical patients.. The perioperative course and clinical outcomes of patients preoperatively receiving ticagrelor + acetylsalicylic acid (ASA) (n = 32) or clopidogrel + ASA (n = 49) until cardiac surgery, performed at University of Goettingen between January 2012 and December 2012, were studied. The study was designed as a retrospective observational study. The observation period started with the surgery and ended after 3 days. P < 0.05 was considered statistically significant.. Preoperative data and intraoperative characteristics were almost similar among the groups. In the first 24 h, the median blood loss was 850 [780-1600] ml in the ticagrelor group and 680 [400-860] ml in the clopidogrel group (P = 0.0006). Furthermore, the median red blood cell transfusion (P = 0.0031), the median pooled platelet transfusion (P = 0.0012), the median prothrombin complex concentrate use (P = 0.0114) and the median fibrinogen use (P = 0.0118) were significantly higher in the ticagrelor group compared with the clopidogrel group. However, there was no statistical significance between the two groups regarding intensive care unit and hospital stay, mechanical ventilation time, incidence of acute kidney injury and mortality. Hence, a tendency towards more rethoracotomies due to bleeding in the ticagrelor group was observed (P = 0.0632).. In cardiac surgical patients who are treated with ticagrelor + ASA until surgery, ticagrelor therapy is associated with a significantly higher blood loss, a significantly higher use of blood products and coagulation factors and higher incidence of rethoracotomies for bleeding compared with patients treated with clopidogrel + ASA.

Topics: Adenosine; Aged; Aged, 80 and over; Aspirin; Blood Transfusion; Coronary Artery Bypass; Female; Hemorrhage; Humans; Male; Middle Aged; Perioperative Period; Platelet Aggregation Inhibitors; Retrospective Studies; Ticagrelor; Treatment Outcome

The choice of antiplatelet therapy after acute coronary syndrome (ACS) is complicated: Ticagrelor and prasugrel are novel alternatives to clopidogrel, patients with some genotypes may not respond to clopidogrel, and low-cost generic formulations of clopidogrel are available.. To determine the most cost-effective strategy for dual antiplatelet therapy after percutaneous coronary intervention for ACS.. Decision-analytic model.. Published literature, Medicare claims, and life tables.. Patients having percutaneous coronary intervention for ACS.. Lifetime.. Societal.. Five strategies were examined: generic clopidogrel, prasugrel, ticagrelor, and genotyping for polymorphisms of CYP2C19 with carriers of loss-of-function alleles receiving either ticagrelor (genotyping with ticagrelor) or prasugrel (genotyping with prasugrel) and noncarriers receiving clopidogrel.. Direct medical costs, quality-adjusted life years(QALYs), and incremental cost-effectiveness ratios (ICERs).. The clopidogrel strategy produced$179 301 in costs and 9.428 QALYs. Genotyping with prasugrel was superior to prasugrel alone, with an ICER of $35 800 per QALY relative to clopidogrel. Genotyping with ticagrelor was more effective than genotyping with prasugrel ($30 200 per QALY relative to clopidogrel). Ticagrelor was the most effective strategy($52 600 per QALY relative to genotyping with ticagrelor).. Stronger associations between genotype and thrombotic outcomes rendered ticagrelor substantially less cost-effective ($104 800 per QALY). Genotyping with prasugrel was the preferred therapy among patients who could not tolerate ticagrelor.. No randomized trials have directly compared genotyping strategies or prasugrel with ticagrelor.. Genotype-guided personalization may improve the cost-effectiveness of prasugrel and ticagrelor after percutaneous coronary intervention for ACS, but ticagrelor for all patients may bean economically reasonable alternative in some settings.

Topics: Acute Coronary Syndrome; Adenosine; Alleles; Aryl Hydrocarbon Hydroxylases; Clopidogrel; Coronary Thrombosis; Cost-Benefit Analysis; Cytochrome P-450 CYP2C19; Decision Support Techniques; Direct Service Costs; Drug Therapy, Combination; Drugs, Generic; Genotype; Hemorrhage; Humans; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Polymorphism, Genetic; Prasugrel Hydrochloride; Quality-Adjusted Life Years; Risk Factors; Thiophenes; Ticagrelor; Ticlopidine

Despite advances in anti-platelet treatments, there still exists an early increase in both ischemic as well as bleeding events following primary PCI in patients with ST-elevation myocardial infarction (STEMI). Platelet inhibition data of different anti-platelet treatments in the acute phase of a myocardial infarction might offer some insight into these problems. The aim of this study was to evaluate the pharmacodynamic profile of 5 different anti-platelet treatments in the acute phase of STEMI in patients undergoing primary PCI.. A total of 223 STEMI patients undergoing primary PCI were prospectively included. Patients received either pre-hospital clopidogrel only, pre-hospital clopidogrel followed by prasugrel switch in the cath lab, prasugrel treatment only, pre-hospital clopidogrel followed by ticagrelor switch in the cath lab or pre-hospital ticagrelor only. Platelet reactivity was measured serially using vasodilator-stimulated phosphoprotein (VASP).. Patients receiving pre-hospital clopidogrel followed by prasugrel switch showed similar platelet inhibition data as patients receiving prasugrel only, with more than 90% being good responders the day after PCI. Average time from prasugrel administration to a VASP value of <50% was 1.5 hours. In patients receiving pre-hospital ticagrelor, 50% were good responders at completion of PCI and average time to a VASP-value of <50% was 2.3 hours. Only 32% of patients receiving clopidogrel only were responders the day after PCI.. Switching from an upstream bolus dose of clopidogrel to prasugrel at the time of PCI, appeared as a safe and feasible option with no tendency for overshoot or attenuation of platelet inhibition. Pre-hospital administration of ticagrelor was associated with a 50% good responder rate at completion of PCI.

Topics: Adenosine; Aged; Blood Platelets; Clinical Protocols; Clopidogrel; Drug Administration Schedule; Electrocardiography; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Thiophenes; Ticagrelor; Ticlopidine

Topics: Acute Coronary Syndrome; Adenosine; Administration, Oral; Clopidogrel; Hemorrhage; Humans; Platelet Activation; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor; Ticlopidine; Treatment Outcome

The PLATO (Platelet Inhibition and Patient Outcomes) randomized trial (NCT00391872) in patients with acute coronary syndromes (ACS) reported that ticagrelor (in addition to aspirin) reduced the rate of the composite end point of myocardial infarction (MI), stroke, or cardiovascular death compared with clopidogrel (in addition to aspirin) by 16% over 12 months (P < 0.001). No significant difference in the incidence of major bleeding was noted, but ticagrelor was associated with a higher rate of major bleeding not related to coronary artery bypass grafting.. By extrapolating the key findings of PLATO, we sought to assess the cost-effectiveness of ticagrelor compared with clopidogrel in the management of ACS in a contemporary Australian setting.. A Markov model with 4 health states (free from further ACS events, MI, stroke, and death) was developed to simulate the long-term costs and outcomes associated with ACS. Event risks were based on data derived directly from PLATO, and costs and utilities were drawn from published sources. A 10-year time horizon was simulated, and future costs and benefits were discounted at a 5% annual rate. However, treatment with ticagrelor and clopidogrel was only assumed for the first 12 months, with no benefits applied beyond drug cessation. Sensitivity analyses were undertaken based on variations to key data inputs. All costs for resource use applied in the analysis were based on published Australian prices (in 2010/2011 dollars [A$]).. Over 10 years, the estimated quality-adjusted life-years lived per-patient were 5.74 and 5.68 for ticagrelor and clopidogrel, respectively. Net costs were A$19,132 for ticagrelor and A$18,428 for clopidogrel. These equated to an incremental cost-effectiveness ratio of A$9031 per quality-adjusted life-year gained for ticagrelor compared with clopidogrel. Sensitivity analyses indicated the result to be robust.. When assessed from the perspective of the Australian health care system, ticagrelor is likely to be cost-effective compared with clopidogrel in preventing downstream morbidity and mortality associated with ACS.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Australia; Clopidogrel; Coronary Artery Bypass; Cost-Benefit Analysis; Drug Costs; Hemorrhage; Humans; Markov Chains; Middle Aged; Platelet Aggregation Inhibitors; Quality-Adjusted Life Years; Ticagrelor; Ticlopidine; Treatment Outcome

To compare hemorrhagic events between clopidogrel and ticagrelor in the Platelet Inhibition and Patient Outcomes (PLATO) trial.. We examined the FDA Medical Review.. Compared to clopidogrel, ticagrelor significantly increased spontaneous bleeds, major bleeds, major plus minor bleeds, and major plus minor plus minimal bleeds. Ticagrelor also increased both major and fatal/life-threatening bleeds versus clopidogrel when CABG was performed between 24 and 96 h after stopping medication, which was also accompanied by a larger volume of chest tube drainage and transfusions. Moreover, ticagrelor increased CABG-related bleeding versus clopidogrel in those patients who did not wait until day 5 after stopping treatment to have CABG. Additionally, compared to clopidogrel, ticagrelor increased the risk of hematuria (RR=1.91; 95% CI: 0.95-3.83), intracranial hemorrhage or subdural or other hematoma (RR 1.87; 95% CI: 1.02-3.42), subcutaneous hemorrhage, ecchymosis, hematoma (RR=1.63; 95% CI: 0.84-3.17), epistaxis (RR=1.49; 95% CI: 0.67-3.32), retroperitoneal hematoma or hemorrhage (RR=1.49; 95% CI: 0.53-4.19), gastrointestinal/anal bleed (RR=1.23; 95% CI: 0.93-1.64) and bleed/hematoma (RR=1.21, 95% CI: 1.02-1.43).. Clopidogrel is safer than ticagrelor in regard to bleeding. Additionally, ticagrelor's purported faster antiplatelet 'offset' is substantially longer than its pharmacokinetics indicate. Considering the fact that the mortality, stent thrombosis and myocardial infarction 'benefit' of ticagrelor have recently been challenged, and that the increase in stroke on ticagrelor has recently been shown to be worse than originally published, the decision to use ticagrelor over clopidogrel in the face of a higher risk for bleeds is not advised.

Topics: Adenosine; Cardiovascular Diseases; Clopidogrel; Dose-Response Relationship, Drug; Hemorrhage; Humans; Incidence; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine

Prasugrel is a third-generation thienopyridine prodrug and ticagrelor is a non-competitive P2Y12 receptor antagonist. In their phase 3 studies, both agents reduced rates of ischemic events relative to treatment with clopidogrel.. The pharmacodynamic profile of anti-platelet effects of prasugrel was compared with that of ticagrelor in rats.. The active metabolite of prasugrel was less potent than ticagrelor and its active metabolite on platelet aggregation in vitro. In contrast, prasugrel was a more potent antiplatelet agent than ticagrelor on ex vivo platelet aggregation: their ED50 values at peak for ADP 20 μmol·L(-1) were 1.9 and 8.0 mg·kg(-1) , respectively. Prasugrel's inhibition of platelet aggregation was maintained for up to 24 h after administration, but ticagrelor's duration of action was substantially shorter. Prasugrel and ticagrelor significantly inhibited thrombus formation with ED50 values of 1.8 and 7.7 mg·kg(-1) , respectively. Both agents also prolonged bleeding times (ED200 values of 3.0 and 13 mg·kg(-1) respectively) suggesting that at equivalent levels of inhibition of platelet aggregation, the agents would show comparable antithrombotic activity with similar bleeding risk. Platelet transfusion significantly increased blood platelet numbers similarly in prasugrel- and ticagrelor-treated rats. In the prasugrel-treated group, platelet transfusion caused significant shortening of bleeding time, while in the ticagrelor-treated group, platelet transfusion showed no influence on bleeding time under the experimental conditions employed.. Prasugrel and ticagrelor showed several differences in their pharmacological profiles and these disparities may reflect their differing reversibility and/or pharmacokinetic profiles.

Topics: Adenosine; Animals; Blood Coagulation Tests; Dose-Response Relationship, Drug; Hemorrhage; Hemostasis; Male; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prodrugs; Purinergic P2Y Receptor Antagonists; Rats; Rats, Sprague-Dawley; Risk; Thiophenes; Thrombosis; Ticagrelor

On July 20, 2011, the Food and Drug Administration (FDA) approved ticagrelor (Brilinta™) for use during acute coronary syndromes. The drug labeling includes a 'black box' warning for bleeding risks, conventional for antithrombotics, and a unique warning that higher than 100 mg/daily maintenance treatment with aspirin may reduce ticagrelor effectiveness. The approval was granted following ticagrelor secondary reviews, and review of complete response by FDA officials.. To summarize the recommendations of different FDA reviewers, and their impact on drug approval.. Review of the Platelet Inhibition and Clinical Outcomes (PLATO) trial comparing the efficacy of ticagrelor versus standard care treatment with clopidogrel. Patients (n = 18,624) with moderate- to high-risk acute coronary syndromes undergoing coronary intervention or being medically managed were randomized to ticagrelor (180-mg loading dose followed by 90 mg twice daily thereafter) or clopidogrel (300-600-mg loading dose followed by 75 mg once daily) for 6-12 months.. The facts outlined in official reviews suggest that ticagrelor has been approved despite objections from both clinical primary reviewers assessing drug efficacy and safety. In addition, the statistical reviewer and cross-discipline team leader also recommended against approval. The putative grounds for their concerns were retrieved from the public FDA records and are briefly outlined here.

Topics: Acute Coronary Syndrome; Adenosine; Clinical Trials, Phase III as Topic; Clopidogrel; Dose-Response Relationship, Drug; Double-Blind Method; Drug Approval; Hemorrhage; Humans; Multicenter Studies as Topic; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Ticagrelor; Ticlopidine; United States; United States Food and Drug Administration

Ticagrelor is a new antiplatelet agent that was pitted against clopidogrel in the Platelet Inhibition and Patient Outcomes (PLATO) trial. Because ticagrelor is the first oral, reversible, twice-daily agent, sufficient information on drug interactions is not available. Our objective was to ascertain the safety of ticagrelor with other common medications. The US Food and Drug Administration Complete Response Review indicates that renal adverse events (AEs) and renal function AEs were higher in ticagrelor-treated patients who were concomitantly treated with angiotensin receptor blockers (ARBs) >50% of study days compared to ticagrelor-treated patients who did not receive ARBs >50% of study days. Clopidogrel-treated patients showed a trend for an increase in adverse renal events with ARB use. However, this was not as pronounced as that observed with ticagrelor. Dyspnea was also significantly increased in patients on concomitant ticagrelor-ARB compared to ticagrelor without concomitant ARB and clopidogrel (21.4% vs 14.6% vs 9.9%, respectively) as well as angioedema (0.15% vs 0.09%). Furthermore, in patients with a baseline estimated glomerular filtration rate (eGFR) <30 mL/min, the risk of major bleeding, death, and renal failure was increased in patients on ticagrelor compared to patients on clopidogrel. In patients on ticagrelor, ARBs significantly increased the frequency of renal related AEs, renal function AEs, and dyspnea. Moreover, in patients with a baseline eGFR <30 mL/min, the risk of major bleeding, death, and renal failure was increased in patients on ticagrelor compared to patients on clopidogrel.

Topics: Adenosine; Angiotensin II Type 1 Receptor Blockers; Clopidogrel; Drug Interactions; Dyspnea; Glomerular Filtration Rate; Hemorrhage; Humans; Kidney; Kidney Diseases; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Ticagrelor; Ticlopidine; United States; United States Food and Drug Administration

Topics: Adenosine; Clopidogrel; Cytochrome P-450 Enzyme System; Genetic Variation; Genotype; Hemorrhage; Humans; Isoenzymes; Pharmacogenetics; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Factors; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Female; Hemorrhage; Humans; Male; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Ticagrelor; Ticlopidine

Topics: Acute Coronary Syndrome; Adenosine; Cardiovascular Diseases; Chronic Disease; Hemorrhage; Humans; Kidney Diseases; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Factors; Ticagrelor

Emergency department physicians, along with hospitalists and interventional cardiologists, provide first-line care for patients experiencing symptoms potentially associated with acute coronary syndromes (ACS). Because these health care providers encounter and manage patients with varying degrees of risk, a clear understanding of the modes of action, benefits, and limitations of various therapeutic options is crucial for achieving optimal outcomes in the acute-care setting. Oral antiplatelet therapy has a major role in the acute care of patients with suspected ACS due to the critical role of platelets in the pathophysiology of disease. The current standard-of-care oral antiplatelet therapy for ACS is aspirin in combination with a P2Y12 adenosine diphosphate (ADP) receptor antagonist, most commonly clopidogrel. Aspirin and P2Y12 antagonists have both demonstrated efficacy in reducing morbidity and mortality in patients with ACS, but are also associated with increased bleeding risk compared with controls. Additionally, despite dual oral antiplatelet therapy, patients remain at substantial residual risk for ischemic events due to thrombotic episodes driven by platelet activation pathways that are not inhibited by these agents, including the protease-activated receptor (PAR)-1 platelet activation pathway, stimulated by thrombin. Novel oral antiplatelet agents in advanced clinical development include a direct and more readily reversible P2Y12 antagonist, ticagrelor, as well as a new class of PAR-1 antagonists, which includes vorapaxar and atopaxar. Ticagrelor has shown a significant ischemic benefit and an increase in non-surgical bleeding over clopidogrel in the large phase 3 Platelet Inhibition and Patient Outcomes trial. Results of phase 2 trials with PAR-1 antagonists suggest that these agents may provide incremental reduction in ischemic events without a bleeding liability. This hypothesis is being evaluated in 2 large ongoing phase 3 trials with vorapaxar, including the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA*CER) trial in patients with non-ST-segment elevation ACS.

Topics: Acute Coronary Syndrome; Adenosine; Administration, Oral; Aspirin; Cardiology; Clopidogrel; Drug Therapy, Combination; Emergency Medicine; Hemorrhage; Hospitalists; Humans; Imines; Lactones; Patient Selection; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Purinergic P2Y Receptor Antagonists; Pyridines; Receptor, PAR-1; Risk Factors; Ticagrelor; Ticlopidine; Treatment Outcome

Topics: Adenosine; Clinical Trials as Topic; Coronary Disease; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor

AZD6140, the first reversible oral P2Y(12) receptor antagonist, exhibits greater and more consistent inhibition of platelet aggregation than the irreversible thienopyridine clopidogrel. As a result of its reversible effect, AZD6140 may pose less risk for bleeding when antiplatelet treatment cannot be stopped at least 5 days before coronary artery bypass graft (CABG) surgery or other invasive procedures. The Dose conflrmation Study assessing anti-Platelet Effects of AZD6140 vs. clopidogRel in NSTEMI (DISPERSE2) trial showed overall comparable bleeding rates with antiplatelet treatment with AZD6140 90 mg twice daily or 180 mg twice daily vs. clopidogrel 75 mg once daily in 984 patients with non-ST-elevation acute coronary syndromes. A post hoc exploratory analysis of bleeding outcomes in the subset of 84 patients undergoing CABG in DISPERSE2 suggests reduced risk for total bleeding (41% and 58% vs. 62%), all major bleeding (38% and 50% vs. 62%), and life-threatening bleeding (22% and 38% vs. 54%) with AZD6140 90 mg (n = 32) and 180 mg (n = 26) vs. clopidogrel (n = 26) respectively. Trends suggested that major bleeding rates were reduced with AZD6140 (combined groups) vs. clopidogrel when treatment was stopped < or = 5 days prior to surgery (39% vs. 63%, p = 0.15) but not when treatment was stopped > 5 days before surgery (50% vs. 60%). This observation is consistent with the reversible binding of AZD6140 to the P2Y(12) receptor. Further prospective studies are planned to assess the relationship between this potential clinical benefit of AZD6140 and the reversibility of its antiplatelet effects.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clinical Trials as Topic; Clopidogrel; Coronary Artery Bypass; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor; Ticlopidine; Treatment Outcome

Topics: Adenosine; Clinical Trials as Topic; Clopidogrel; Coronary Thrombosis; Cost-Benefit Analysis; Hemorrhage; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Prognosis; Purinergic P2 Receptor Antagonists; Pyridines; Risk Assessment; Survival Rate; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

The P2Y12 receptor has proven to be a key target in the prevention of complications associated with atherosclerotic vascular disease especially in the context of acute coronary syndrome and percutaneous coronary intervention in addition to aspirin. Three generations of thienopyridines, ticlopidine, clopidogrel, and prasugrel have proven efficacy in the prevention of ischemic vascular events but with increased bleeding. The concept of individualized tailored therapy has recently emerged with the discovery of the diminished effect of some thienopyridine among carriers of the loss-of-function cytochrome (CYP) P4502C19*2 variant. Non-thienopyridine P2Y12 antagonists have also recently demonstrated that these benefits are not limited to one class of agents or may be generalizable to reversible antagonists of this receptor. Future rational use of these agents will require attention to disease and patient features to strike the optimal balance of benefit to risk.

Topics: Acute Coronary Syndrome; Adenosine; Angioplasty, Balloon, Coronary; Aspirin; Atherosclerosis; Coronary Artery Bypass; Hemorrhage; Humans; Piperazines; Platelet Aggregation Inhibitors; Postoperative Complications; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2Y12; Stroke; Thiophenes; Ticagrelor

Topics: Acute Coronary Syndrome; Adenosine; Angioplasty, Balloon, Coronary; Clinical Trials, Phase III as Topic; Clopidogrel; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Ticagrelor; Ticlopidine; Treatment Outcome

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Coronary Artery Bypass; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Stroke; Ticagrelor; Ticlopidine

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Research Design; Ticagrelor; Ticlopidine