ticagrelor and Myocardial-Infarction

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

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

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

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

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

Clopidogrel is the most frequently used P2Y12 inhibitor as a component of the dual antiplatelet regimen in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Prior studies have shown the variable efficacy of clopidogrel due to genotypic differences in the CYP2C19 enzyme function, which converts clopidogrel to its active metabolite. The aim of this meta-analysis is to evaluate the effectiveness of genotype testing-guided P2Y12 inhibitor prescription therapy to patients after PCI for ACS compared to non-genotype guided conventional treatment.. A comprehensive literature search was performed in PubMed, Embase, and Cochrane to identify relevant trials. Summary effects were calculated using a DerSimonian and Laird random-effects model as odds ratio with 95% confidence intervals for all the clinical endpoints.. Seven studies with 9617 patients were included. Genotype-guided strategy arm included prasugrel or ticagrelor prescription to patients with loss of function (LOF) of CYP219 alleles (most commonly alleles being *2 and *3) and clopidogrel prescription to those without the LOF allele. The conventional arm included patients treated with clopidogrel without genotype testing. Comparison of genotype arm with conventional arm showed decreased major adverse cardiovascular events (MACE), improved cardiovascular (CV) mortality, and reduced incidence of myocardial infarction (MI) in the genotype arm, and a similar stroke incidence in the two arms. Regarding adverse events, the incidence of stent thrombosis was lower in the genotype arm than the conventional arm.. Our analysis illustrates the possible advantages of genotype-guided P2Y12 inhibitor prescription strategy compared to non-genotype-guided strategy with reductions in MACE, CV mortality, MI, and stent thrombosis. This analysis can be used as a stepping stone to conducting further trials determining the efficacy of this treatment strategy in various ACS subtypes.

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

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

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

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

To explore the effects of morphine on P2Y. PubMed, Embase, Cochrane Library, and Web of Science were used to retrieve literature through 11th May 2019. Standardized weighted mean difference (SMD) and relative risk (RR) with 95% confidence intervals (CI), P-value, and I. A total of 13 articles were included in this study, containing 5688 patients (morphine group: n = 2014, control group: n = 3674). Results illustrated that the morphine group had a higher platelet reactivity (SMD: 0.834, 95%CI: 0.483-1.186, P < 0.001) and HRPR rate (RR: 1.994, 95%CI: 1.536-2.588, P < 0.001) than the control group, while the Cmax of ticagrelor (WMD: -481.838, 95%CI: -841.242-122.434, P = 0.009) was lower than that of the control group. The death rate of the morphine group was lower than that in the control group (RR: 0.561, 95%CI: 0.337-0.933, P = 0.026). The morphine group had a higher emesis rate than the control group (RR: 4.486, 95%CI: 2.263-8.891, P < 0.001).. Morphine effectively suppresses the inhibition effect of P2Y

Topics: Analgesics, Opioid; Drug Interactions; Humans; Morphine; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Ticagrelor

Topics: Clopidogrel; Coronary Artery Disease; Elective Surgical Procedures; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Perioperative Care; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor

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

Clinical guidelines recommend extended treatment with dual antiplatelet therapy (DAPT) with ticagrelor 60 mg (twice daily) beyond 12 months in high-risk patients with a history of myocardial infarction (MI) who have previously tolerated DAPT and are not at heightened bleeding risk. However, evidence on patterns of use and associated clinical outcomes in routine clinical practice is limited.. ALETHEIA is an observational, multi-country study, designed to describe characteristics, treatment persistence, and bleeding and cardiovascular (CV) outcomes in post-MI patients who initiate ticagrelor 60 mg in routine clinical practice (NCT04568083). The study will include electronic health data in the United States (US; Medicare, commercial claims) and Europe (Sweden, Italy, United Kingdom, Germany). Characteristics will be described among patients with and without ticagrelor 60 mg ≥1 year post-MI. Assuming an a priori threshold of 5000 person-years on-treatment is met, to ensure sufficient precision, clinical outcomes (bleeding and CV events) among patients treated with ticagrelor 60 mg will be assessed. Risk factors for clinical outcomes and treatment discontinuation will be assessed in patients with ticagrelor 60 mg and meta-analysis used to combine estimates across databases. Cohort selection will initiate from the ticagrelor 60 mg US and European approval dates and end February 2020. An estimated total of 7250 patients prescribed ticagrelor 60 mg are expected to be included.. An increased understanding of patterns of ticagrelor 60 mg use and associated clinical outcomes among high-risk patients with a prior MI is needed. The a priori specified stepwise approach adapted in this observational study is expected to generate useful evidence for clinical decision-making and treatment optimization.

Topics: Aged; Aspirin; Humans; Medicare; Myocardial Infarction; Observational Studies as Topic; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome; United States

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

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 (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

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

Various antiplatelet drugs are used following Acute Coronary Syndromes (ACS). Of them, adenosine diphosphate receptor P2Y12 inhibitors clopidogrel, prasugrel and ticagrelor are currently used for post-ACS long-term treatment. Although they act on the same receptor, they differ in pharmacodynamics and pharmacokinetics. Several enzymes and transporters involved in the metabolism of P2Y12 inhibitors show genetic variability with functional impact. This includes Pglycoprotein, carboxylesterase 1 and, most notably, CYP2C19 that is important in clopidogrel activation. Common gain-of-function or loss-of-function alleles of CYP2C19 gene are associated with lower or higher platelet reactivity that may impact clinical outcomes of clopidogrel treatment. Prasugrel is considered to be less dependent on CYP2C19 variability as it is also metabolized by other CYP450 isoforms. Some studies, however, showed the relevance of CYP2C19 variants for platelet reactivity during prasugrel treatment as well. Ticagrelor is metabolized mainly by CYP3A4, which does not show functionally relevant genetic variability. Its concentrations may be modified by the variants of Pglycoprotein gene ABCB1. While no substantial difference between the clinical efficacy of prasugrel and ticagrelor has been documented, both of them have been shown to be superior to clopidogrel in post-ACS treatment. This can be partially explained by lower variability at each step of their metabolism. It is probable that factors influencing the pharmacokinetics of both drugs, including genetic factors, may predict the clinical efficacy of antiplatelet treatment in personalized medicine.. We summarize the pharmacokinetics and pharmacogenetics of P2Y12 inhibitors with respect to their clinical effects in post-myocardial infarction treatment.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B; Biotransformation; Blood Platelets; Clopidogrel; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP3A; Drug Resistance; Humans; Myocardial Infarction; Pharmacogenomic Variants; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Ticagrelor; Treatment Outcome

Antithrombotic treatment is a key component of secondary prevention following acute coronary syndromes (ACS). Although dual antiplatelet therapy is standard therapy post-ACS, duration of treatment is the subject of ongoing debate. Prolonged dual antiplatelet therapy in high-risk patients with history of myocardial infarction reduced the risk of recurrent myocardial infarction, stroke or cardiovascular death. Similarly, in patients with stable coronary artery disease, two-thirds of whom had a history of myocardial infarction, dual antithrombotic therapy with very-low-dose rivaroxaban and aspirin also resulted in improved ischaemic outcomes. In the absence of head-to-head comparison, choosing the most appropriate treatment strategy can be challenging, particularly when it comes to balancing the risks of ischaemia and bleeding. We aim to review the evidence for currently available antithrombotic treatments and provide a practical algorithm to aid the decision-making process.

Topics: Acute Coronary Syndrome; Aged; Algorithms; Aspirin; Cardiovascular Diseases; Coronary Artery Disease; Decision Making; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk; Rivaroxaban; Secondary Prevention; Stroke; Ticagrelor

Topics: Aged, 80 and over; Clopidogrel; Desensitization, Immunologic; Drug Eruptions; Drug Substitution; Female; Glucocorticoids; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Skin; Skin Tests; Ticagrelor

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

To estimate the absolute treatment effects of newer P2Y. We searched Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials of oral P2Y. From 9277 articles, nine fulfilled our inclusion criteria. Three trials compared newer P2Y. Newer P2Y

Topics: Acute Coronary Syndrome; Adolescent; Adult; Aged; Clopidogrel; Female; Humans; Male; Middle Aged; Myocardial Infarction; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Factors; Scotland; Sex Characteristics; Ticagrelor; Treatment Outcome; Young Adult

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 National Institute for Health and Care Excellence (NICE) invited AstraZeneca, the manufacturer of ticagrelor (Brilique

Topics: Aspirin; Cost-Benefit Analysis; Drug Therapy, Combination; England; Humans; Models, Economic; Myocardial Infarction; Platelet Aggregation Inhibitors; Quality-Adjusted Life Years; Secondary Prevention; Technology Assessment, Biomedical; Thrombosis; Ticagrelor; Wales

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

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

Newer P2Y12 inhibitors have more rapid onset of platelet inhibition compared with clopidogrel, especially the intravenous P2Y12 inhibitor cangrelor. Direct comparisons between cangrelor and oral P2Y12 inhibitors ticagrelor and prasugrel do not exist. Thus, we performed a network meta-analysis to directly and indirectly compare different P2Y12 inhibitors in patients undergoing percutaneous coronary intervention (PCI).. MEDLINE/PubMed and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared at least two P2Y12 inhibitors including cangrelor, clopidogrel, prasugrel, and ticagrelor. Network meta-analysis with a Bayesian approach was performed to directly and indirectly compare the effects of the aforementioned P2Y12 inhibitors on clinical outcomes. Odds ratios with credible intervals (OR [CrIs]) were generated with random-effects models to compare outcomes.. This analysis included 15 RCTs with 54,025 patients randomized to cangrelor (n=12,475), clopidogrel (n=26,903), prasugrel (n=7455), or ticagrelor (n=7192) at time of PCI. Patients had a mean age of 63±10, 74% were male, and 82% underwent PCI for acute coronary syndrome. No significant differences between cangrelor and clopidogrel were found with respect to cardiovascular death (OR 1.01 [CrI 0.23-4.39]), myocardial infarction (OR 0.94 [CrI 0.69-1.25]), major adverse cardiac events (OR 0.91 [CrI 0.69-1.18]), stent thrombosis (OR 0.66 [CrI 0.37-1.19]), or major bleeding (OR 1.52 [CrI 0.79-2.98]). Rank probability data suggested that ticagrelor and prasugrel were better than cangrelor for reducing ischemic events, though these differences were not significant.. Despite rapid platelet inhibition provided by cangrelor, newer oral P2Y12 inhibitors such as ticagrelor and prasugrel have comparable clinical outcomes.

Topics: Adenosine; Adenosine Monophosphate; Clopidogrel; Humans; Myocardial Infarction; Network Meta-Analysis; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; Treatment Outcome

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

Recent trials have examined the effect of prolonged dual antiplatelet therapy (DAPT) in a variety of patient populations, with heterogeneous results regarding benefit and safety, specifically with regard to cardiovascular and non-cardiovascular mortality. We performed a meta-analysis of randomized trials comparing more than a year of DAPT with aspirin alone in high-risk patients with a history of prior myocardial infarction (MI).. A total of 33 435 patients were followed over a mean 31 months among one trial of patients with prior MI (63.3% of total) and five trials with a subgroup of patients that presented with, or had a history of, a prior MI (36.7% of total). Extended DAPT decreased the risk of major adverse cardiovascular events compared with aspirin alone (6.4 vs. 7.5%; risk ratio, RR 0.78, 95% confidence intervals, CI, 0.67-0.90; P = 0.001) and reduced cardiovascular death (2.3 vs. 2.6%; RR 0.85, 95% CI 0.74-0.98; P = 0.03), with no increase in non-cardiovascular death (RR 1.03, 95% CI 0.86-1.23; P = 0.76). The resultant effect on all-cause mortality was an RR of 0.92 (95% CI 0.83-1.03; P = 0.13). Extended DAPT also reduced MI (RR 0.70, 95% CI 0.55-0.88; P = 0.003), stroke (RR 0.81, 95% CI 0.68-0.97; P = 0.02), and stent thrombosis (RR 0.50, 95% CI 0.28-0.89; P = 0.02). There was an increased risk of major bleeding (1.85 vs. 1.09%; RR 1.73, 95% CI 1.19-2.50; P = 0.004) but not fatal bleeding (0.14 vs. 0.17%; RR 0.91, 95% CI 0.53-1.58; P = 0.75).. Compared with aspirin alone, DAPT beyond 1 year among stabilized high-risk patients with prior MI decreases ischaemic events, including significant reductions in the individual endpoints of cardiovascular death, recurrent MI, and stroke. Dual antiplatelet therapy beyond 1 year increases major bleeding, but not fatal bleeding or non-cardiovascular death.

Topics: Adenosine; Adult; Aged; Clopidogrel; Drug Therapy, Combination; Humans; Long-Term Care; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Secondary Prevention; Ticagrelor; Ticlopidine; Treatment Outcome; Young Adult

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

Topics: Adenosine; Drug Interactions; Humans; Morphine; Myocardial Infarction; Observational Studies as Topic; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Ticagrelor; Treatment Outcome

Ticagrelor (P2Y12 receptor antagonist) is presently indicated for preventing atherothrombotic events in patients with acute coronary syndrome and patients with a history of myocardial infarction. The PARTHENON clinical development program comprises five randomized, controlled, cardiovascular, indication-seeking outcome studies, aiming to evaluate ticagrelor across the spectrum of patients with atherothrombotic disease. Results of two large-scale trials support a benefit for ticagrelor in patients with acute coronary syndrome (PLATO; ClinicalTrials.gov: NCT00391872) and in patients with a history of myocardial infarction (PEGASUS-TIMI 54; ClinicalTrials.gov: NCT01225562). Ongoing trials will provide information on the efficacy and safety of ticagrelor in patients with acute ischemic stroke or transient ischemic attack (SOCRATES; ClinicalTrials.gov: NCT01994720), peripheral artery disease (EUCLID; ClinicalTrials.gov: NCT01732822) and coronary artery disease in patients with Type 2 diabetes mellitus (THEMIS: ClinicalTrials.gov: NCT01991795).

Topics: Acute Coronary Syndrome; Adenosine; Atherosclerosis; Diabetes Mellitus, Type 2; Humans; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Ticagrelor; Treatment Outcome

The immediate administration of oral antiplatelet therapy in the form of aspirin plus a P2Y12 inhibitor is the universally recognised standard of care for patients who present with acute myocardial infarction. Despite strong recommendations for their use, there are a paucity of data describing their onset of action and clinical efficacy during the short time frames from confirmation of diagnosis to reperfusion with primary percutaneous coronary intervention.. To complete a systematic review evaluating the currently available evidence regarding the pharmacokinetic and pharmacodynamic activity of orally administered clopidogrel, prasugrel and ticagrelor during the acute phase of a myocardial infarction in relation to mechanical reperfusion with primary percutaneous coronary angioplasty.. We searched PubMed and EMBASE databases up to January 2016 using the terms outlined in our search strategy.. Twelve papers were included in our final analysis; seven relating to pharmacodynamic studies, one to a pharmacokinetic study and four to pharmacokinetic/pharmacodynamic studies.. Our results indicate that despite the administration of oral P2Y12 inhibitors including newer more potent agents that should allow for greater and more consistent levels of platelet inhibition, the physiological state of ST segment elevation MI (STEMI) and the co-administration of opioid based analgesia are associated with a reduction in the degree of platelet inhibition achieved following their administration.

Topics: Adenosine; Administration, Oral; Clopidogrel; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine

Physicians considering prescription of P2Y12-receptor antagonist for long-term (>1 year) protection of patients post-myocardial infarction face the trilemma of selecting between clopidogrel, prasugrel, or ticagrelor. Differential ischemic benefits derived from relevant trials may assist in tailoring treatment, although the different bleeding definitions applied make any meaningful comparison of each agent's bleeding potential very difficult. Considering the available data and recognizing the significant limitation of observations obtained thus far from subgroup analyses, prasugrel appears to provide higher anti-ischemic protection than clopidogrel. Ticagrelor seems to be an attractive option for patients with renal dysfunction, peripheral arterial disease, or following a brief P2Y12-receptor antagonist interruption, whereas clopidogrel may be advised in the presence of cost and availability issues. As head-to-head comparative trials between P2Y12-receptor antagonists are lacking, selection of a specific agent by the clinician should be made on the basis of critical appraisal of available large clinical datasets.

Topics: Adenosine; Clopidogrel; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Stroke; Ticagrelor; Ticlopidine; Time Factors

ST-elevated myocardial infarction (STEMI) holds the highest early mortality among patients with acute coronary syndromes. Despite numerous claims of clinical benefits and superiority over clopidogrel, there are no head-to-head outcome randomized clinical trials (RCTs) directly comparing novel antithrombotic agents in STEMI. Moreover, since most regulatory approvals are based on a single RCT's results, their meta-analyses are rare to compare death rates. We analyzed the 30-day mortality in STEMI patients who underwent percutaneous coronary intervention (PCI) and were treated with antithrombotic agents compared to clopidogrel as a reference.. Altogether, 10 RCT's and 1 retrospective study with a total number of 26,658 STEMI patients were included. Random-effects model with Mantel-Heanszel weighting was used to pool outcomes into a meta-analysis. Therapy with clopidogrel was associated with 2.76% 30-day STEMI mortality which was similar to that of ticagrelor (2.6%; OR=0.9395 [CI=0.76 to 1.17; p=0.58]), and for bivalirudin (2.8%; OR=1.02 [CI=0.82 to 1.27; p=0.86]), but was slightly higher for heparin (3.0%; OR=1.08 [CI=0.86 to 1.35; p=0.52]). There was a trend towards lower mortality after tirofiban (2.1%; OR=0.77 [CI=0.52 to 1.13; p=0.20]), and cangrelor (1.7%; OR=0.59 [CI=0.29 to 1.20; p=0.19]), although the sample size for both agents was woefully small. The only agent which offers a significant 30-day mortality benefit in STEMI was prasugrel with significant lowest 1.75% death rate (OR=0.63 [CI=0.46 to 0.86; p=0.03]).. Among antithrombotic agents, prasugrel, but not ticagrelor, offers significant 30-day mortality benefit over clopidogrel in PCI-treated STEMI patients justifying short-term use in such a high-risk population.

Topics: Adenosine; Clopidogrel; Electrocardiography; Female; Humans; Male; Middle Aged; Myocardial Infarction; Outcome Assessment, Health Care; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Survival Analysis; Ticagrelor; Ticlopidine

Rapid and consistent platelet inhibition represents the cornerstone of pharmacologic treatment in the early hours of ST-segment elevation myocardial infarction (STEMI). Oral P2Y12 inhibitors are recommended to be administered as early as possible in patients with STEMI undergoing primary percutaneous coronary intervention. However, a delay in the onset of antiplatelet agent effects has been recently described in the first several hours after oral administration of clopidogrel, prasugrel, and ticagrelor. As a result, primary percutaneous coronary intervention is performed in most cases with P2Y12 inhibition that may be inadequate. Several strategies may be applied in order to "bridge the gap" in platelet inhibition after oral P2Y12 inhibitors in STEMI, such as upstream administration of P2Y12 inhibitors, loading dose modification, use of an intravenous P2Y12 inhibitor, or glycoprotein IIb/IIIa inhibitors' administration. These strategies may further improve clinical outcomes in this high-risk "golden window."

Topics: Adenosine; Clopidogrel; Early Medical Intervention; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

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

Antiplatelets play a significant role in the management of patients with coronary disease. Novel inhibitors of the platelet P2Y12 receptor have more rapid, potent, and consistent inhibitory effect on platelets compared with clopidogrel. Evidence from large clinical studies have defined populations in which novel agents are superior to clopidogrel. Ticagrelor or prasugrel in addition to aspirin should be used preferentially for patients with ST-elevation myocardial infarction because of significant anti-ischemic benefits. In patients with non-ST segment elevation acute coronary syndromes, ticagrelor has proven superiority over clopidogrel whether or not an invasive strategy is adopted, and prasugrel has been shown to be beneficial when started at the time of percutaneous coronary intervention. Of note, neither prasugrel nor ticagrelor have been studied in patients who underwent percutaneous coronary intervention for stable coronary disease or those who required 'triple therapy.' In these situations, clopidogrel should remain the default until further data are available. Prolonged use of clopidogrel in patients with drug-eluting stents beyond 12 months is emerging as a novel indication for the agent.

Topics: Acute Coronary Syndrome; Adenosine; Algorithms; Angioplasty, Balloon, Coronary; Clopidogrel; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Precision Medicine; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine

Spontaneous coronary artery dissection (SCAD) is an increasingly recognised cause of acute coronary syndrome, particularly in women. A 36-year-old Caucasian woman presented to our hospital with sudden onset chest pain and was diagnosed with a non-ST elevation myocardial infarction. Coronary angiography revealed mid and distal left anterior descending artery (LAD) dissection with distal LAD occlusion. A short segment of apical LAD filled late with incomplete opacification (Thrombolysis In Myocardial Infarction (TIMI) 1 flow). A decision was made to treat the patient conservatively, with subsequent resolution of dissection over the next 3 months. Our patient made a good clinical recovery with healing of her affected coronary vasculature on subsequent angiogram. The case illustrates that SCAD can be managed conservatively with antiplatelet agents, β-blockers, heparin and statins, if the patient is haemodynamically stable and coronary flow is adequate.

Topics: Adenosine; Adult; Anticholesteremic Agents; Antihypertensive Agents; Aspirin; Atorvastatin; Carbazoles; Carvedilol; Coronary Angiography; Coronary Vessel Anomalies; Diagnosis, Differential; Echocardiography; Electrocardiography; Female; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Propanolamines; Purinergic P2Y Receptor Antagonists; Ticagrelor; Vascular Diseases

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

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

P2Y12 receptor antagonist therapy is recommended in addition to ASA for up to 1 year after acute coronary syndrome to reduce ischemic events. In contrast, the benefit of long-term dual antiplatelet therapy beyond 1 year remains unclear. Ticagrelor is a potent, reversibly binding P2Y12 receptor-antagonist that has been shown to be superior to clopidogrel in patients with acute coronary syndromes for up to 1 year.. PEGASUS-TIMI 54 is a randomized, double-blind, placebo-controlled, multinational clinical trial designed to evaluate the efficacy and safety of ticagrelor in addition to aspirin (75-150 mg) for the prevention of major adverse cardiovascular events in patients with a history of myocardial infarction and risk factors. Patients with a history of spontaneous myocardial infarction within 1 to 3 years are randomized in a 1:1:1 fashion to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or matching placebo, all with low dose ASA, until the end of the study. The primary endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. Recruitment began in October 2010 and completed in April 2013 with a sample size of over 21,000 patients. The trial is planned to continue until the latest of either 1,360 adjudicated primary end points are accrued or the last patient randomized has been followed for at least 12 months.. PEGASUS-TIMI 54 is investigating whether the addition of intensive antiplatelet therapy with ticagrelor to low-dose aspirin reduces major adverse cardiovascular events in high-risk patients with a history of myocardial infarction.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Multicenter Studies as Topic; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Thrombolytic Therapy; Ticagrelor

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

In the peripheral arteries, a thrombus superimposed on atherosclerosis contributes to the progression of peripheral artery disease (PAD), producing intermittent claudication (IC), ischemic necrosis, and, potentially, loss of the limb. PAD with IC is often undiagnosed and, in turn, undertreated. The low percentage of diagnosis (∼30%) in this setting of PAD is of particular concern because of the potential worsening of PAD (amputation) and the high risk of adverse vascular outcomes (vascular death, coronary artery disease, stroke). A Medline literature search of the highest-quality systematic reviews and meta-analyses of randomized controlled trials documents that, due to risk of bias, imprecision, and indirectness, the overall quality of the evidence concerning diagnostic tools and antithrombotic interventions in PAD is generally low. Areas of research emerge from the information collected. Appropriate treatments for PAD patients will only derive from ad-hoc studies. Innovative imaging techniques are needed to identify PAD subjects at the highest vascular risk. Whether IC unresponsive to physical exercise and smoking cessation identifies those with a heritable predisposition to more severe vascular events deserves to be addressed. Devising ways to improve prevention of vascular events in patients with PAD implies a co-ordinated approach in vascular medicine.

Topics: Adenosine; Aspirin; Asymptomatic Diseases; Cilostazol; Clopidogrel; Fibrinolytic Agents; Humans; Intermittent Claudication; Ischemia; Lower Extremity; Meta-Analysis as Topic; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Primary Prevention; Review Literature as Topic; Secondary Prevention; Stroke; Tetrazoles; Thrombosis; Ticagrelor; Ticlopidine

The 3 main clinical manifestations of acute coronary syndrome (ACS) are unstable angina, non-ST-segment myocardial infarction, and ST-segment myocardial infarction. Together they comprise a major cause of emergency care and hospitalization in the United States. Consequently, all hospital-based physicians should be familiar with current recommendations regarding the diagnosis and management of ACS. Effective inhibition of platelet activation and aggregation is central to the treatment of ACS, and dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is recommended in all patients with ACS. Recently, the American Heart Association and American College of Cardiology Foundation published focused updates to their guidelines for the management of ACS patients. These updates included changes in antiplatelet therapy arising from the introduction of prasugrel and ticagrelor as alternatives to clopidogrel for the P2Y12 inhibitor component of dual antiplatelet therapy. Among the P2Y12 inhibitors recommended for each indication, the guidelines do not advocate any one P2Y12 inhibitor over another, but instead recommend that therapy is individualized based on each patient's demographic and clinical characteristics. This article presents a clinical case study to illustrate the hospital management of ST-segment myocardial infarction and unstable angina/non-ST-segment myocardial infarction with particular reference to the latest changes in antiplatelet therapy guidelines. This article outlines key differences in the indications and recommendations for P2Y12 inhibitors and summarizes clinical data from the pivotal studies of prasugrel and ticagrelor.

Topics: Acute Coronary Syndrome; Adenosine; Age Factors; Aspirin; Body Weight; Clopidogrel; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Quality of Health Care; Randomized Controlled Trials as Topic; Thiophenes; Ticagrelor; Ticlopidine

Despite the improvement in stent technology, stent thrombosis (ST), a potentially catastrophic event, still occurs. Among several risk factors for ST, high on-treatment platelet reactivity to clopidogrel has been demonstrated to play a role, occurring in about one-third of the patients. In order to overcome this limitation, prasugrel and ticagrelor, newer P2Y12 inhibitors, have been developed and approved for clinical use. Two large clinical trials, TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel-thrombolysis in myocardial infarction (TRITON-TIMI) 38 and Study of Platelet Inhibition and Patient Outcomes (PLATO), evaluated these drugs in patients with acute coronary syndrome (ACS), showing a significant improvement in efficacy end points (including a prominent reduction in ST occurrence) compared to clopidogrel. In contrast, the TRILOGY ACS trial found no benefit with prasugrel compared to clopidogrel in patients with medically treated ACS. The aim of this review is to consider decision-making strategies between prasugrel and ticagrelor in daily clinical practice.

Topics: Acute Coronary Syndrome; Adenosine; Coronary Thrombosis; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Stents; Thiophenes; Ticagrelor

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

Ticagrelor is a potent P2Y12 adenosine diphosphate receptor antagonist characterized by a rapid onset, consistent and reversible antiplatelet effect, and an acceptable safety profile compared with existing adenosine diphosphate receptor blockers. In the large Phase III trial, PLATO, ticagrelor significantly reduced the composite of cardiovascular death, myocardial infarction, or stroke as well as cardiovascular and all-cause mortality compared with clopidogrel in patients presenting with acute coronary syndromes. With its favorable impact on mortality, ticagrelor changes the landscape of anti-thrombotic therapy for patients with acute coronary syndromes.

Topics: Acute Coronary Syndrome; Adenosine; Animals; Clinical Trials, Phase III as Topic; Clopidogrel; Humans; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Stroke; Ticagrelor; Ticlopidine

Topics: Acute Coronary Syndrome; Adenosine; Drug Administration Schedule; Drug Costs; Humans; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Stroke; Thrombosis; Ticagrelor; United States

Administration of a P2Y 12 -receptor antagonist in addition to aspirin is mandatory in patients with acute coronary syndromes (ACS) or undergoing percutaneous coronary intervention (PCI) to reduce the occurrence of thrombotic events; however, their impact on mortality and stroke is unclear. We aimed to evaluate the influence of moderate (clopidogrel) or potent (prasugrel/ticagrelor) P2Y 12 -receptor inhibition on major cardiovascular outcomes among patients with ACS or undergoing PCI. Systematic literature search was performed to find randomised, controlled clinical trials comparing the clinical impact of clopidogrel with placebo or prasugrel/ticagrelor versus clopidogrel. Outcome measures included cardiovascular death, myocardial infarction (MI), total stroke and intracranial haemorrhage (ICH). Random-effects model with Mantel-Heanszel weighting was used to pool outcomes into a meta-analysis. Four studies comparing clopidogrel with placebo and five trials comparing clopidogrel with new P2Y 12 -receptor inhibitors were identified including a total of 107,473 patients. Compared to placebo, clopidogrel reduced the risk of cardiovascular death (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.87-0.99, p=0.02), MI (OR 0.80; 95%CI 0.74-0.88, p<0.00001) and stroke (OR 0.84; 95%CI 0.72-0.97, p=0.02), without influencing risk for ICH (OR 0.96; 95%CI 0.69-1.33, p=0.79). Treatment with prasugrel/ticagrelor provided additional benefit over clopidogrel regarding cardiovascular mortality (OR 0.86; 95%CI 0.78-0.94, p=0.002) and MI (OR: 0.83; 95%CI 0.74-0.93, p<0.001), but no advantage in stroke (OR: 1.06; 95%CI 0.88-1.26, p=0.55) and in ICH (OR: 1.16; 95%CI 0.75-1.81; p=0.49) was observed. Increased potency of P2Y 12 -receptor inhibition is associated with decreased risk in cardiovascular death and MI; however, this association is not true in case of stroke, where potent P2Y 12 -receptor antagonists have no incremental benefit over clopidogrel.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Coronary Thrombosis; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Assessment; Risk Factors; Stroke; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

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

Non-ST elevation acute coronary syndromes are responsible for approximately 1 million admissions to U.S. hospitals and twice as many to European hospitals each year. Thus, they are among the most common serious illnesses in adults, and are associated with an in-hospital mortality of approximately 5%. The most common cause is rupture of an atherosclerotic coronary plaque, resulting in subtotal coronary occlusion. Diagnosis is based on the clinical picture of retrosternal chest pain, aided by electrocardiographic findings of ST segment deviations and biomarker abnormalities (elevation of troponin and natriuretic peptides) and cardiac imaging (myocardial scans showing perfusion defects). Treatment involves antiischemic agents (nitrates and β blockers), antiplatelet drugs (aspirin, P2Y(12), and glycoprotein IIb/IIIa receptor blockers), and anticoagulants (unfractionated and low-molecular-weight heparins). Patients should undergo risk stratification, and those with high-risk factors should undergo coronary arteriography promptly with the intent to carry out coronary revascularization. Those at low risk should continue to receive intensive antiischemic and antithrombotic therapy. At discharge, patients should receive intensive lipid-lowering therapy with high doses of a statin, as tolerated.

Topics: Acute Coronary Syndrome; Adenosine; Angina, Unstable; Anticoagulants; Aspirin; Clopidogrel; Coronary Angiography; Echocardiography; Electrocardiography; Humans; Myocardial Infarction; Myocardial Revascularization; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Factors; Thiophenes; Ticagrelor; Ticlopidine

Ticagrelor is a new oral antagonist of the platelet P2Y₁₂ receptor that offers several potential advantages compared to clopidogrel including faster and more effective inhibition of platelet aggregation. Ticagrelor has been compared to clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) trial in a broad population of patients with acute coronary syndrome showing a reduction of the 12-month risk of death from vascular causes, myocardial infarction and stroke without increasing the overall risk of major bleeding. In a subanalysis of the PLATO trial focusing on patients with ST-elevation myocardial infarction, ticagrelor results were consistent with those of the overall trial. Additionally, possible pleiotropic effects of ticagrelor, including an appealing interaction with adenosine, might constitute a specific advantage in this particular subset of patients.

Topics: Adenosine; Animals; Arrhythmias, Cardiac; Evidence-Based Medicine; Heart Failure; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor

ADP plays a pivotal role in localized platelet activation and recruitment, and, with that, in the maintenance of thrombus integrity, making it a suitable target for the control of intravascular thrombosis. The limited distribution of one of its receptors, the P2Y12 receptor, primarily to platelets makes it an especially attractive pharmacologic target. For the last several decades the thienopyridine family of P2Y12 antagonists have provided the vast majority of clinical data confirming the clinical benefit of selective P2Y12 inhibition. Recently, new thienopyridine plus nonthienopyridine P2Y12 antagonists have become available or are being studied that will further improve our treatment of patients with coronary disease.

Topics: Acute Coronary Syndrome; Adenosine; Adenosine Monophosphate; Clopidogrel; Coronary Artery Disease; Humans; Myocardial Infarction; Piperazines; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Quinazolinones; Stents; Sulfonamides; Thiophenes; Thrombosis; Ticagrelor; Ticlopidine

Topics: Adenosine; Angina, Unstable; Anticoagulants; Blood Glucose; Guideline Adherence; Humans; Kidney Failure, Chronic; Myocardial Infarction; Patient Education as Topic; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Practice Guidelines as Topic; Prasugrel Hydrochloride; Proton Pump Inhibitors; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor

For many years clopidogrel was the 'gold standard' ADP receptor antagonist in patients with coronary artery disease in combination with acetylsalicylic acid, i.e. in elective/stable patients after coronary stent implantation and in patients with acute coronary syndromes with/without percutaneous coronary intervention. For the latter group, in which the risk of atherothrombotic events is increased, the new ADP receptor-antagonists, e.g. prasugrel and ticagrelor, have shown their superiority over clopidogrel. This is mainly based on the fact that up to 30% of patients with acute coronary syndromes tend to be low- or non-responders to therapy due to non-genetic and/or genetic causes. Nevertheless, there is still room for the use of clopidogrel in the majority of patients with coronary artery disease. This review summarizes the latest knowledge of clopidogrel and its current indications.

Topics: Adenosine; Aspirin; Clopidogrel; Coronary Artery Disease; Drug Therapy, Combination; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

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

Acute coronary syndromes reflect a spectrum of disease related, most commonly, to the sudden reduction in blood flow to a portion of myocardium. The underlying pathogenesis of the reduction in coronary flow is related to the sudden rupture of an atherosclerotic plaque, with subsequent thrombus formation leading to either vascular occlusion or microembolization. Clinicians combat this process with antithrombotic therapy, which typically includes both anticoagulant and antiplatelet therapy, and mechanical therapies, such as percutaneous coronary interventions, nearly always using stents. This review focuses on P2Y12 antagonists as one component of our armamentarium of antiplatelet therapies, specifically on data addressing in whom, when, which agent, and in what dose such agents should be administered.

Topics: Acute Coronary Syndrome; Adenosine; Angina, Unstable; Aspirin; Humans; Integrin alpha2; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Ticagrelor

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

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

Aggressive intravenous and oral dual antiplatelet therapy has established primary percutaneous coronary intervention (PCI) as the standard of care for acute myocardial infarction. Clopidogrel is currently the thienopyridine of choice for dual antiplatelet therapy in patients treated with PCI. The dose regime and duration of therapy of clopidogrel has undergone multiple refinements. Recently, 2 novel third generation oral inhibitors of P2Y12 receptors, prasugrel and ticagrelor, have undergone clinical evaluation with promising results. This article is a non-exhaustive review of the literature, concentrating on the role of current and novel oral antiplatelet agents for acute myocardial infarction particularly highlighting the limitations and issues associated with clopidogrel use.

Topics: Adenosine; Angioplasty, Balloon, Coronary; Clopidogrel; Drug Therapy, Combination; Electrocardiography; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Thiophenes; Ticagrelor; Ticlopidine

Topics: Adenosine; Angioplasty, Balloon, Coronary; Clinical Trials as Topic; Clopidogrel; Coronary Angiography; Coronary Disease; Coronary Occlusion; Coronary Restenosis; Drug-Eluting Stents; Foramen Ovale, Patent; Hospital Mortality; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Radiology, Interventional; Thiophenes; Thrombolytic Therapy; Ticagrelor; Ticlopidine; Treatment Outcome

Platelets possess three P2 receptors for adenine nucleotides: P2Y1 and P2Y12, which interact with ADP, and P2X1, which interacts with ATP. The interaction of adenine nucleotides with their platelet receptors plays an important role in thrombogenesis. The thienopyridine ticlopidine, an antagonist of the platelet P2Y12 ADP receptor, reduces the incidence of vascular events in patients at risk, but it also has some important drawbacks: a relatively high incidence of toxic effects; delayed onset of action; high inter-individual variability in response. Another thienopyridine, clopidogrel, has superseded ticlopidine, because it is an efficacious antithrombotic drug and is less toxic than ticlopidine. However, the high inter-patient variability in response still remains an important issue. These drawbacks justify the continuing search for agents that can further improve the clinical outcome of patients with atherosclerosis through greater efficacy and/or safety. A new thienopyridyl compound prasugrel, which is characterized by higher potency and faster onset of action compared with clopidogrel, is currently under clinical evaluation. Two direct and reversible P2Y12 antagonists, cangrelor and AZD6140, have very rapid onset and reversal of platelet inhibition, which make them attractive alternatives to thienopyridines, especially when rapid inhibition of platelet aggregation or its quick reversal are required. Along with new P2Y12 antagonists, inhibitors of the other platelet receptor for ADP, P2Y1, and of the receptor for ATP, P2X1, are under development and may prove to be effective antithrombotic agents.

Topics: Adenosine; Adenosine Monophosphate; Angina, Unstable; Animals; Blood Platelets; Clopidogrel; Coronary Disease; Coronary Thrombosis; Drug Interactions; Fibrinolytic Agents; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Randomized Controlled Trials as Topic; Receptors, Purinergic P2; Receptors, Purinergic P2X; Syndrome; Thiophenes; Ticagrelor; Ticlopidine

Platelets play a central role in the pathophysiology of acute coronary syndromes (ACS). Dual antiplatelet therapy has resulted in significant advances in the treatment of ACS; however, ACS remains an important cause of morbidity and mortality. Important limitations exist among the current antiplatelet agents and therefore a pressing need for the development of improved antiplatelet agents exists. Three antiplatelet agents currently under investigation (prasugrel, AZD6140, and cangrelor) in clinical trials for the treatment of ACS appear promising.

Topics: Adenosine; Adenosine Monophosphate; Angina, Unstable; Blood Platelets; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Thiophenes; Ticagrelor; Treatment Outcome

Guidelines recommend that dual antiplatelet therapy using aspirin and clopidogrel should be administered to the majority of patients with acute coronary syndromes, including those undergoing percutaneous coronary intervention (PCI). However, the results of a large randomized, placebo-controlled study suggest that a 300-mg loading dose of clopidogrel must be administered at least 15 h prior to PCI in order to achieve a significant reduction in peri-PCI thrombotic events. Other data suggest that 2 h of pretreatment may be sufficient if a 600-mg loading dose is used. Since it is often difficult to achieve an adequate pretreatment goal with clopidogrel in clinical practice, more rapid achievement of platelet P2Y(12) inhibition may improve patient outcomes. Prasugrel, [6-[2-(3,4-diflurophenyl) cyclopropyl1-1-y1] amino-2-propylthio-9-D-ribofuranosyl-9H-purine (AZD6140), and cangrelor are platelet P2Y(12) receptor antagonists currently in development that offer faster acting inhibition of adenosine diphosphate (ADP)--induced platelet aggregation. These agents act upon the same platelet receptor as clopidogrel, but are distinguished by their routes of administration, reversibility, and pharmacodynamic properties. Prasugrel is an orally administered agent that provides faster, higher, and more consistent inhibition of platelet aggregation than clopidogrel. The results of Phase II testing suggest that the risk of bleeding is similar in prasugrel- and clopidogrel-treated patients. AZD6140 is another orally administered platelet inhibitor with rapid and reversible action. Again, Phase II testing suggests similar bleeding risk for clopidogrel. Preliminary evidence suggests that clinical outcomes may be better in prasugrel- and AZD6140-treated patients than in clopidogrel-treated patients. Cangrelor is an intravenously administered, reversible, short-acting agent with a rapid onset of activity. Bleeding risk and clinical outcomes data are similar in cangrelor- and abciximab-treated patients. The results of ongoing Phase III clinical trials involving more than 40,000 patients will demonstrate whether these agents fulfill their potential to improve outcomes in PCI-treated patients by providing faster, higher, and more consistent inhibition of platelet aggregation.

Topics: Adenosine; Angioplasty, Balloon, Coronary; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Clinical Trials as Topic; Clopidogrel; Coronary Disease; Dose-Response Relationship, Drug; Humans; Membrane Proteins; Myocardial Infarction; Platelet Aggregation; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2Y12; 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

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

THEMIS is a double-blind, randomized trial of 19,220 patients with diabetes mellitus and stable coronary artery disease (CAD) comparing ticagrelor to placebo, in addition to aspirin. The present study aimed to describe the proportion of patients eligible and reasons for ineligibility for THEMIS within a population of patients with diabetes and CAD included in the Reduction of Atherothrombosis for Continued Health (REACH) registry.. The THEMIS eligibility criteria were applied to REACH patients. THEMIS included patients ≥50 years with type 2 diabetes and stable CAD as determined by either a history of previous percutaneous coronary intervention, coronary artery bypass grafting, or documentation of angiographic stenosis of ≥50% of at least one coronary artery. Patients with prior myocardial infarction or stroke were excluded. In REACH, 10,156 patients had stable CAD and diabetes. Of these, 6515 (64.1%) patients had at least one exclusion criteria. From the remaining population, 784 patients did not meet inclusion criteria (7.7%) mainly due to absence of aspirin treatment (7.2%), yielding a 'THEMIS-eligible population' of 2857 patients (28.1% of patients with diabetes and stable CAD). The main reasons for exclusion were a history of myocardial infarction (53.1%), use of oral anticoagulation (14.5%), or history of stroke (12.9%). Among the 4208 patients with diabetes and a previous PCI, 1196 patients (28.4%) were eligible for inclusion in the THEMIS-PCI substudy.. In a population of patients with diabetes and stable coronary artery disease, a sizeable proportion appear to be 'THEMIS eligible.'. http://www.. gov identifier: NCT01991795.

Topics: Aspirin; Coronary Artery Disease; Diabetes Mellitus, Type 2; Humans; Myocardial Infarction; Outcome Assessment, Health Care; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

This study aimed to compare the outcomes of aspirin in combination with either ticagrelor or clopidogrel after off-pump coronary artery bypass (OPCAB) in patients with clopidogrel resistance.. Between November 2014 and November 2020, 1739 patients underwent OPCAB. Aspirin and clopidogrel treatment was initiated the day after surgery. On postoperative days 7 to 9, clopidogrel resistance was evaluated using a point-of-care assay. A total of 278 (18.9%) patients had clopidogrel resistance ( platelet reaction unit >208) and were enrolled in the study. The study investigators excluded patients with coresistance to aspirin (n = 74) and divided the remaining patients (mean age, 67.4 ± 8.5 years) into 2 groups (an aspirin and ticagrelor group [AT group; n = 102] and an aspirin and clopidogrel group [AC group; n = 102]), randomly assigned using a 1:1 ratio block table. The primary end point was graft patency and major adverse cardiovascular events (MACEs; defined as the composite of cardiovascular mortality, myocardial infarction, and repeat revascularization at 1 year after OPCAB), and the coprimary end point was the graft patency rate. The data were analyzed using the intent-to-treat method.. The graft occlusion rates in the AT and AC groups were 3.9% and 5.9%, respectively (P = .52). Neither death from cardiovascular causes (1.0% vs 2.9%; P = .32) nor myocardial infarction showed significant differences (1.0% vs 3.9%; P = .18). No significant difference in the rates of major bleeding were found between the 2 groups (P = .75). However, the AT group was associated with a lower rate of MACEs after OPCAB (hazard ratio, 0.77; 95% CI, 0.684-0.891; P = .01).. These results suggest that ticagrelor may be associated with reducing MACEs in patients with clopidogrel resistance after OPCAB.

Topics: Aged; Aspirin; Clopidogrel; Coronary Artery Bypass, Off-Pump; Humans; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; 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

Acute myocardial ischaemia triggers a non-specific inflammatory response of remote myocardium through the increase of plasma concentrations of acute-phase proteins, which causes myocardial oedema. As ticagrelor has been shown to significantly decrease circulating levels of several pro-inflammatory cytokines in patients after acute myocardial infarction with ST-elevation (STEMI), we sought to investigate a potential suppressive effect of ticagrelor over prasugrel on cardiac magnetic resonance (CMR) T1 and T2 values in remote myocardium.. Ninety STEMI patients were prospectively included and randomised to receive either ticagrelor or prasugrel maintenance treatment after successful primary percutaneous coronary intervention. Patients underwent CMR after 2-7 days. The protocol included long and short axis cine imaging, T1 mapping, T2 mapping and late gadolinium enhancement imaging.. After excluding 30 patients due to either missing images or insufficient quality of the T1 or T2 maps, 60 patients were included in our analysis. Of those, 29 patients were randomised to the ticagrelor group and 31 patients to the prasugrel group. In the remote myocardium, T1 values did not differ between groups (931.3 [919.4-950.4] ms for ticagrelor vs. 932.6 [915.5-949.2] ms for prasugrel (p = 0.94)), nor did the T2 values (53.8 ± 4.6 ms for ticagrelor vs. 53.7 ± 4.7 ms for prasugrel (p = 0.86)). Also, in the infarcted myocardium, T1 and T2 values did not differ between groups.. In revascularised STEMI patients, ticagrelor maintenance therapy did not show superiority over prasugrel in preventing early remote myocardial inflammation as assessed by CMR T1 and T2 mapping.

Topics: Arrhythmias, Cardiac; Contrast Media; Gadolinium; Humans; Inflammation; Magnetic Resonance Spectroscopy; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Predictive Value of Tests; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Thrombin generation (TG), platelet function and circulating endothelial progenitor cells (EPCs) have an important role in the pathophysiology of coronary artery disease (CAD). To date, the effect of novel P2Y. Comparing the effects of prasugrel and ticagrelor on TG and EPCs in the acute phase of ST-segment elevation myocardial infarction (STEMI).. STEMI patients were randomized to either ticagrelor or prasugrel treatment. TG, platelet reactivity and EPCs were evaluated prior to P2Y. Between December 2018 - July 2021, 83 consecutive STEMI patients were randomized to ticagrelor (N = 42) or prasugrel (N = 41) treatment. No differences were observed at T0 for all measurements. P2Y. Among STEMI patients, prasugrel as compared to ticagrelor was associated with more potent TG inhibition and improved EPCs count and function.

Topics: Adenosine; Endothelial Progenitor Cells; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Thrombin; Ticagrelor; Treatment Outcome

The role of percutaneous coronary interventions (PCI) in patients with diabetes mellitus and multi-vessel disease has been questioned by the results of the FREEDOM trial, which showed superiority of coronary artery bypass graft(CABG) over first generation drug-eluting stents (DES) including a reduction in mortality. In the light of safer and more efficacious stents and significantly better medical management, those results that date back to 2012 need to be revisited. TUXEDO-2 is a study designed to compare two contemporary stents in Indian diabetic patients with multi-vessel disease.. The primary objective of the TUXEDO-2 study is to compare the clinical outcomes of PCI with ultra-thin Supraflex Cruz vs Xience when combined with contemporary optimal medical therapy (OMT) in diabetic patients with multi-vessel disease. The secondary objective is to compare clinical outcomes between a pooled cohort from both arms of the study (Supraflex Cruz + Xience; PCI arm) vs CABG based on a performance goal derived from the CABG arm of the FREEDOM trial (historical cohort). The tertiary objective is a randomized comparison of ticagrelor vs prasugrel in addition to aspirin for the composite of ischemic and bleeding events.. In this prospective, open-label, multi-centre, 2 × 2 factorial, randomized, controlled study, 1,800 patients with diabetes mellitus and multi-vessel disease (inclusion criteria similar to FREEDOM trial) with indication for coronary revascularization will be randomly assigned to Supraflex Cruz or Xience stents and also to ticagrelor- or prasugrel- based antiplatelet strategies. All patients will receive guideline directed OMT and optimal PCI including image- and physiology-guided complete revascularization where feasible. The patients will be followed through five years to assess their clinical status and major clinical events. The primary endpoint is a non-inferiority comparison of target lesion failure at one-year for Supraflex Cruz vs Xience (primary objective) with an expected event rate of 11% and a non-inferiority margin of 4.5%. For PCI vs CABG (secondary objective), the primary endpoint is major adverse cardiac events (MACE), defined as a composite of all cause death, nonfatal myocardial infarction, or stroke at one-year and yearly up to five years, with a performance goal of 21.6%. For ticagrelor vs prasugrel (tertiary objective), the primary endpoint is composite of death, myocardial infarction, stroke, and major bleeding as per the Bleeding Academic Research Consortium (BARC) at one-year with expected event rate of 15% and a non-inferiority margin of 5%.. The TUXEDO-2 study is a contemporary study involving state-of-the-art PCI combined with guideline directed OMT in a complex subset of patients with diabetes mellitus and multi-vessel disease. The trial will answer the question as to whether a biodegradable polymer coated ultra-thin Supraflex Cruz stent is an attractive option for PCI in diabetic patients with multi-vessel disease. It will also help address the question whether the results of FREEDOM trial would have been different in the current era of safer and more efficacious stents and modern medical therapy. In addition, the comparative efficacy and safety of ticagrelor vs prasugrel in addition to aspirin will be evaluated. (CTRI/2019/11/022088).

Topics: Aspirin; Coronary Artery Disease; Diabetes Mellitus; Everolimus; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Prospective Studies; Stroke; Ticagrelor; Treatment Outcome

Both ticagrelor and prasugrel are class I recommendations for treatment of ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) [ 1 ]. But clinical outcomes with the two drugs are conflicting which might be due to differential effects on coronary microcirculation. No study to date had compared the effects of prasugrel or ticagrelor on coronary microcirculation in patients undergoing pharmacoinvasive PCI (pPCI).. To compare the effects of prasugrel and ticagrelor on coronary microcirculation in STEMI patients undergoing pPCI as assessed by Myocardial Blush Grade (MBG). The secondary aim was to assess flow in the infarct-related artery by corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC) and whether a differential effect if detected on coronary microcirculation translated in improvement in left ventricular ejection fraction assessed at 6 months.. A total of 240 patients with STEMI were evaluated in this open-label randomized control trial who initially underwent thrombolysis and later PCI (from 24 to 48 h) post-successful thrombolysis. The study subjects were randomized to receive either ticagrelor ( n  = 120) or prasugrel ( n  = 120) in 1 : 1 ratio 2 h prior to elective PCI. Patients underwent PCI according to standard protocol and post-procedure cTFC and MBG were compared. Patients were also followed up for 6 months to compare ejection fractions in both groups. We also assessed the effect of the two drugs on bleeding complications during hospitalization and over 6-month follow-up period.. There were no significant differences between the two groups with respect to baseline characteristics. Prasugrel administration resulted in higher MBG Grade 3 (50.86% vs 33.89%, P  = 0.012) and lower cTFC (17.14 ± 4.08 vs 19.3 ± 4.06, P  < 0.01). Improvement in ejection fraction was significantly higher with prasugrel compared to ticagrelor (10.29% ± 15.2 vs 4.66% ± 13.5, P  = 0.003). Bleeding events at 6 months follow-up according to TIMI classification were similar in both the groups (11.86% vs 6.9%, P  = 0.39).. Prasugrel produces greater improvement in coronary microcirculation than Ticagrelor resulting in improved myocardial salvage in patients of STEMI undergoing pPCI.

Topics: Humans; Microcirculation; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; ST Elevation Myocardial Infarction; Stroke Volume; Ticagrelor; Treatment Outcome; Ventricular Function, Left

Repeat coronary revascularization is a common adverse event after successful percutaneous coronary intervention. This analysis aimed to assess the effects of ticagrelor monotherapy on repeat clinically driven revascularization (CDR). 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 randomly allocated to aspirin or placebo for 1 year. The primary end point of this analysis was CDR within 12 months after randomization. The key secondary end points were major adverse cardiovascular and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, stroke, or CDR, and net adverse clinical events (NACEs), including the individual components of MACCEs and clinically relevant bleeding. The analysis was performed in the per-protocol population. CDR occurred in 473 of 7,039 patients and was associated with a significantly higher risk of subsequent all-cause death, myocardial infarction, or stroke (adjusted hazard ratios [HRs] 2.92, 95% confidence interval [CI] 1.82 to 4.67). Ticagrelor monotherapy was associated with a similar 12-month risk of CDR (7.1% vs 6.6%; HR 1.09, 95% CI 0.90 to 1.30, p = 0.363) and MACCEs (8.9% vs 8.6%; HR 1.04, 95% CI 0.89 to 1.22, p = 0.619), and a lower risk of NACEs (12.2% vs 14.6%; HR 0.83 95% CI 0.73 to 0.94, p = 0.004) than ticagrelor plus aspirin. In conclusion, among high-risk patients who underwent percutaneous coronary intervention, ticagrelor monotherapy after 3 months of ticagrelor-based dual antiplatelet therapy was associated with a similar risk of CDR and MACCEs and a decrease of NACEs (TWILIGHT: NCT02270242).

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

Regional variations exist in the epidemiology of peripheral artery disease (PAD), in comorbidities, use of secondary prevention, and outcomes. Large studies of these variations in worldwide populations are rare. The EUCLID (Examining Use of tiCagreLor In peripheral artery Disease) trial included 13,885 patients with PAD from four geographical regions (Central/South America, Europe, Asia, North America) and compared monotherapy with ticagrelor and clopidogrel. Inclusion criteria were either an ankle-brachial index < 0.80 or a prior revascularization. The primary efficacy endpoint was time to first occurrence of any event in the composite of cardiovascular death, myocardial infarction, or ischemic stroke and did not differ between the study arms. This post hoc analysis of EUCLID confirmed that regional differences occurred in the inclusion criteria with more prior revascularization in North America (73.9%) and Asia (72.5%) compared with Central/South America (34.0%) and Europe (51.6%). The characteristics of patients also differed. Prior amputation at baseline was most frequent in Central/South America (6.3%) compared with other regions (1.6-2.8%). A history of stroke was most common in Asia, coronary heart disease in North America, and diabetes in Central/South America compared with other regions. The incidence of outcomes in patients with PAD varied by region. North America had the highest rate of the primary combined endpoint (5.97 events/100 patient-years). Corresponding rates were 4.80, 3.95, and 3.87 for Asia, Europe, and Central/South America, respectively. Hospitalization for acute limb ischemia (events/100 patient-years) was most frequent in Europe (0.75) and North America (0.74) compared with Asia (0.60) and Central/South America (0.33). Adjustment for inclusion criteria and relevant PAD characteristics did not have a major impact on these regional differences. Further adjustment for concomitant disease, risk factors, and preventive medication modified the regional differences only marginally. In conclusion, substantial regional differences were found in cardiovascular and limb outcomes in patients with PAD and were not explained by variation in the category of included patients, concomitant disease, risk factors, and prevention. Such differences, which may be due to variation in other factors such as background population rates or clinical care, need to be considered when designing and interpreting large international studies (

Topics: Clopidogrel; Humans; Internationality; Ischemia; Ischemic Stroke; Myocardial Infarction; Peripheral Arterial Disease; Ticagrelor; Treatment Outcome

The aim of this study was to evaluate if patients with prior myocardial infarction (MI) could benefit from ticagrelor monotherapy in terms of bleeding reduction without any compromise in ischemic event prevention.. Patients with history of MI who undergo percutaneous coronary intervention (PCI) remain at risk for recurrent ischemic events. The optimal antithrombotic strategy for this cohort remains debated.. In this prespecified analysis of the randomized TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, the authors evaluated the impact of history of MI on treatment effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients undergoing PCI with drug-eluting stent with at least 1 clinical and 1 angiographic high-risk feature and free from adverse events at 3 months after index PCI. The primary endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, and the key secondary endpoint was the composite of all-cause death, MI, or stroke, both at 12 months after randomization.. Ticagrelor monotherapy is associated with significantly lower risk for bleeding events compared with ticagrelor plus aspirin, without any compromise in ischemic prevention, among high-risk patients with history of MI undergoing PCI. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242).

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

Whether the access site influences the comparative efficacy and safety of ticagrelor and prasugrel in patients with acute coronary syndrome (ACS) undergoing invasive treatment strategy remains unstudied.. This post-hoc analysis included ACS patients undergoing invasive treatment via radial or femoral access and randomized to either ticagrelor or prasugrel in the ISAR-REACT 5 trial. The primary efficacy endpoint was the composite of death, myocardial infarction (MI) or stroke, safety endpoint was BARC 3 to 5 bleeding. Outcomes were assessed out to 12 months after randomization.. Out of 4018 patients, 3984 underwent invasive treatment via radial or femoral access. 1479 had coronary angiography via radial access (ticagrelor, N = 748; prasugrel, N = 731) and 2505 via femoral access (ticagrelor, N = 1245; prasugrel, N = 1260). There was no interaction between access route and assignment to either ticagrelor or prasugrel regarding the primary efficacy or safety endpoints (P for interaction≥0.616). In the radial group, the primary efficacy endpoint (7.6% versus 5.8%, HR: 1.32 [0.88-1.97], P = 0.151) and the safety endpoint (4.3% versus 3.0%, HR: 1.36, [0.73-1.31], P = 0.300) were not statistically different in patients receiving either ticagrelor or prasugrel. In the femoral group, the primary efficacy endpoint occurred more frequently in patients assigned to ticagrelor as compared to prasugrel (10.3% versus 7.3%, HR: 1.44 [1.10-1.88], P = 0.006) without significant difference in terms of safety endpoint (6.4% versus 5.8%, HR: 1.14, [0.81-1.60], P = 0.470).. In patients with ACS undergoing an invasive treatment strategy, the access route does not influence the comparative efficacy and safety of ticagrelor and prasugrel.. NCT01944800.

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

Clopidogrel has been demonstrated to be effective in improving coronary microcirculation (CM) among patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolytics. Ticagrelor is a more potent adenosine diphosphate (ADP) receptor blocker proven to be superior to clopidogrel among patients with acute coronary syndromes. The present study aimed to compare the effects of ticagrelor and clopidogrel on CM in patients with STEMI treated with fibrinolytics.. The present study prospectively included 48 patients participating in the TREAT trial, which randomly assigned patients with STEMI undergoing fibrinolysis to ticagrelor versus clopidogrel. The primary endpoint of this study was the evaluation of the CM using the global myocardial perfusion score index (global MPSI) obtained by myocardial contrast echocardiography (MCE). Platelet aggregation to ADP was evaluated by Multiplate® and expressed as area under the curve (AUC).. The global MPSI demonstrated no differences between the groups [mean 1.4 (1.2-1.5) in the ticagrelor group and 1.2 (1.2-1.5) in the clopidogrel group (p = 0.41)]. Platelet aggregability was lower in the ticagrelor group (18.1 ± 9.7 AUC), compared to the clopidogrel group (26.1 ± 12.5 AUC, p = 0.01).. We found no improvement in coronary microcirculation with ticagrelor compared to clopidogrel among patients with STEMI treated with fibrinolytics, despite the fact that platelet aggregation to ADP was lower with ticagrelor.. NCT03104062.

Topics: Adenosine Diphosphate; Clopidogrel; Humans; Microcirculation; Myocardial Infarction; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; 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

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

Several studies have suggested that proton pump inhibitors (PPIs) may reduce the antiplatelet effects of clopidogrel and/or aspirin, possibly leading to cardiovascular events.. We aimed to investigate the association between PPI and clinical outcomes in patients treated with ticagrelor monotherapy or conventional antiplatelet therapy after percutaneous coronary intervention (PCI).. This is a subanalysis of the randomized GLOBAL LEADERS trial, comparing the experimental antiplatelet arm (23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy [DAPT]) with the reference arm (12-month aspirin monotherapy following 12-month DAPT) after PCI. Patient-oriented composite endpoints (POCEs: all-cause mortality, myocardial infarction, stroke, or repeat revascularization) and its components were assessed stratified by PPI use as a time-dependent covariate in patients with the experiment or reference antiplatelet arm.. In contrast to conventional antiplatelet strategy, there were no evidence suggesting the interaction between ticagrelor monotherapy and PPIs on increased cardiovascular events, which should be confirmed in further studies.. URL: https://clinicaltrials.gov.

Topics: Aspirin; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Ticagrelor; Treatment Outcome

In the setting of ST-segment elevation myocardial infarction (STEMI), the faster and stronger antiplatelet action of ticagrelor compared to clopidogrel, as well as its pleiotropic effects, could result in a greater degree of cardioprotection and final infarct size (FIS) limitation. The aim of our study was to comparatively evaluate the effect of ticagrelor and clopidogrel on myocardial salvage index (MSI) in STEMI patients undergoing thrombolysis.. Forty-two STEMI patients treated with thrombolysis were randomized to receive clopidogrel (n = 21) or ticagrelor (n = 21), along with aspirin. Myocardial area at risk (AAR) was calculated according to the BARI and the APPROACH jeopardy scores. FIS was quantified by cardiac magnetic resonance imaging (CMR) performed 5-6 months post-randomization. MSI was calculated as (AAR-FIS)/AAR × 100%. Primary endpoint of our study was MSI. Secondary endpoints were FIS and CMR-derived left ventricular ejection fraction (LVEF) at 5 -6 months post-randomization.. By using the BARI score for AAR calculation, mean MSI was 52.25 ± 30.5 for the clopidogrel group and 54.29 ± 31.08 for the ticagrelor group (p = 0.83), while mean MSI using the APPROACH score was calculated at 51.94 ± 30 and 53.09 ± 32.39 (p = 0.9), respectively. Median CMR-derived FIS-as a percentage of LV-was 10.7% ± 8.25 in the clopidogrel group and 12.09% ± 8.72 in the ticagrelor group (p = 0.6). Mean LVEF at 5-6 months post-randomization did not differ significantly between randomization groups.. Our results suggest that the administration of ticagrelor in STEMI patients undergoing thrombolysis offer a similar degree of myocardial salvage, compared to clopidogrel.

Topics: Clopidogrel; Humans; Myocardial Infarction; ST Elevation Myocardial Infarction; Stroke Volume; Thrombolytic Therapy; Ticagrelor; Ventricular Function, Left

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

Despite lipid-lowering and antiplatelet therapy, the pattern of residual lipoproteins seems relevant to long-term cardiovascular outcomes. This study aims to evaluate the effects of combined therapies, commonly used in subjects with acute myocardial infarction, in the quality of low-density lipoprotein (LDL) particles.. Prospective, open-label trial, included patients with acute myocardial infarction. Patients were randomized to antiplatelet treatment (ticagrelor or clopidogrel) and subsequently to lipid-lowering therapy (rosuvastatin or simvastatin/ezetimibe) and were followed up for six months. Nonlinear optical properties of LDL samples were examined by Gaussian laser beam (Z-scan) to verify the oxidative state of these lipoproteins, small angle X-ray scattering (SAXS) to analyze structural changes on these particles, dynamic light scattering (DLS) to estimate the particle size distribution, ultra violet (UV)-visible spectroscopy to evaluate the absorbance at wavelength 484 nm (typical from carotenoids), and polyacrylamide gel electrophoresis (Lipoprint) to analyze the LDL subfractions.. Simvastatin/ezetimibe with either clopidogrel or ticagrelor was associated with less oxidized LDL, and simvastatin/ezetimibe with ticagrelor to lower cholesterol content in the atherogenic subfractions of LDL, while rosuvastatin with ticagrelor was the only combination associated with increase in LDL size.. The quality of LDL particles was influenced by the antiplatelet/lipid-lowering strategy, with ticagrelor being associated with the best performance with both lipid-lowering therapies. Trial registration: NCT02428374.

Topics: Anticholesteremic Agents; Clopidogrel; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoproteins; Myocardial Infarction; Prospective Studies; Rosuvastatin Calcium; Scattering, Small Angle; Simvastatin; Ticagrelor; X-Ray Diffraction

In patients with acute coronary syndrome (ACS), there is residual and variable risk of recurrent ischemic events.. This study aimed to develop biomarker-based prediction models for 1-year risk of cardiovascular (CV) death and myocardial infarction (MI) in patients with ACS undergoing percutaneous coronary intervention.. We included 10,713 patients from the PLATO (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome) trial in the development cohort and externally validated in 3,508 patients from the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial. Variables contributing to risk of CV death/MI were assessed using Cox regression models, and a score was derived using subsets of variables approximating the full model.. An 8-item score for the prediction of CV death/MI was developed and validated for patients with ACS undergoing percutaneous coronary intervention. The ABC-ACS ischemia score showed good calibration and discrimination and might be useful for risk prediction and decision support in patients with ACS. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872; Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Participants With Acute Coronary Syndrome [TRACER]; NCT00527943).

Topics: Acute Coronary Syndrome; Biomarkers; Clopidogrel; Growth Differentiation Factor 15; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; 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

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

Platelet inhibition induced by P2Y12 receptor antagonists in patients with ST-elevation myocardial infarction (STEMI) can be affected by concomitant use of opioids. The aim of this trial was to examine the effect of intravenous (iv) acetaminophen compared with iv fentanyl on P2Y12 receptor inhibition in patients with STEMI.. The Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME 3) trial randomized 195 STEMI patients who were scheduled to undergo primary percutaneous coronary intervention (PCI) and were pre-treated with crushed ticagrelor to iv acetaminophen (N = 98) or iv fentanyl (N = 97) in the ambulance. The primary endpoint, consisting of the level of platelet reactivity units (PRU) measured immediately after primary PCI, was not significantly different between the study arms [median PRU 104 (IQR 37-215) vs. 175 (63-228), P = 0.18]. However, systemic levels of ticagrelor were significantly higher in the acetaminophen arm at the start of primary PCI [151 ng/mL (32-509) vs. 60 ng/mL (13-206), P = 0.007], immediately after primary PCI [326 ng/mL (94-791) vs. 115 ng/mL (38-326), P = 0.002], and at 1 h after primary PCI [488 ng/mL (281-974) vs. 372 ng/mL (95-635), P = 0.002]. Acetaminophen resulted in the same extent of pain relief when compared with fentanyl [reduction of 3 points on 10-step-pain scale before primary PCI (IQR 1-5)] in both study arms (P = 0.67) and immediately after PCI [reduction of 5 points (3-7); P = 0.96].. The iv acetaminophen in comparison with iv fentanyl was not associated with significantly lower platelet reactivity in STEMI patients but resulted in significantly higher ticagrelor plasma levels and was effective in pain relief.

Topics: Analgesics, Opioid; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor

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

In patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), the risk of ischaemic complications is highest in the early phase (during the first 30 days), while most bleeding events occur predominantly during the maintenance phase of treatment (after the first 30 days). Data on the de-escalation of dual antiplatelet therapy by switching from ticagrelor to clopidogrel in stabilised AMI patients are limited. The aim of this study is to investigate the efficacy and safety of switching from ticagrelor to clopidogrel in AMI patients with no adverse event during the first month after the index PCI with newer-generation DES.. TALOS-AMI is a multicentre, randomised, open-label study enrolling 2,590 AMI patients with no adverse events during the first month after the index PCI. One month after the index PCI, eligible patients are randomly assigned either to 1) aspirin 100 mg plus clopidogrel 75 mg daily, or to 2) aspirin 100 mg plus ticagrelor 90 mg twice daily, in a 1:1 ratio. The primary endpoint is a composite of cardiovascular death, MI, stroke, and bleeding type 2, 3 or 5 according to the Bleeding Academic Research Consortium (BARC) criteria from 1 to 12 months after the index PCI.. The TALOS-AMI trial is the first large-scale, multicentre, randomised study exploring the efficacy and safety of the de-escalation of antiplatelet therapy by switching from ticagrelor to clopidogrel in stabilised AMI patients undergoing PCI.

Topics: Acute Coronary Syndrome; Clopidogrel; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; 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

Untargeted metabolomics is used to refine the development of biomarkers for the diagnosis of cardiovascular disease. Myocardial infarction (MI) has major individual and societal consequences for patients, who remain at high risk of secondary events, despite advances in pharmacological therapy. To monitor their differential response to treatment, we performed untargeted plasma metabolomics on 175 patients from the platelet inhibition and patient outcomes (PLATO) trial treated with ticagrelor and clopidogrel, two common P

Topics: Acute Coronary Syndrome; Aged; Blood Platelets; Clopidogrel; Fatty Acids, Unsaturated; Female; Humans; Lipid Metabolism; Male; Metabolomics; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

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

The aim of this study was to investigate the impact of ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) for bifurcation lesions.. GLOBAL LEADERS was a randomized, superiority, all-comers trial comparing 1-month DAPT with ticagrelor and aspirin followed by 23-month ticagrelor monotherapy (experimental treatment) with standard 12-month DAPT followed by 12-month aspirin monotherapy (reference treatment) in patients treated with a biolimus A9-eluting stent. The primary endpoint was a composite of all-cause death or new Q-wave myocardial infarction (MI) at 2 years.. Among the 15,845 patients included in this subgroup analysis, 2,498 patients (15.8%) underwent PCI for at least one bifurcation lesion. The incidence of the primary endpoint was similar between the bifurcation and nonbifurcation groups (4.7 vs. 4.0%, p = .083). The experimental treatment had no significant effect on the primary endpoint according to the presence/absence of a bifurcation lesion (bifurcation: hazard ratio [HR]: 0.74, 95% confidence interval [CI]: 0.51-1.07; nonbifurcation: HR: 0.90, 95% CI: 0.76-1.07, p for interaction = .343), but was associated with significant reduction in definite or probable stent thrombosis (p for interaction = .022) and significant excess of stroke (p for interaction = .018) when compared with the reference treatment.. After PCI for bifurcation lesions using 1-month of DAPT followed by ticagrelor monotherapy for 23 months did not demonstrate explicit benefit regarding all-cause death or new Q-wave MI as in the overall trial.

Topics: Aged; Drug Administration Schedule; Drug-Eluting Stents; Dual Anti-Platelet Therapy; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; Recurrence; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Given that patients with prior myocardial infarction and features of high ischemic and low bleeding risk may benefit by extending dual antiplatelet therapy beyond 1 year, we aimed of assessing platelet reactivity provided by ticagrelor 60 mg bid versus prasugrel 5 mg od in 20 such patients participating in a randomized, crossover study. The primary end point of platelet reactivity at the end of the two treatment periods (by VerifyNow, in PRU) was significantly lower for ticagrelor (31.9 PRU [95% CI 12.3-51.4]) compared with prasugrel (132.1 PRU [111.9-152.3]) with a least squares mean difference of -100.2 PRU (72.1-128.3,

Topics: Aged; Cross-Over Studies; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor

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

Ticagrelor and prasugrel are novel and potent P2Y12 inhibitors. Ticagrelor 90mg or 60mg twice daily is known to reduce ischemic events but be associated with an increased risk of bleeding in patients with prior myocardial infarction in Western countries. Although ticagrelor 90mg twice daily was tested in a randomized clinical trial in East Asia, the clinical significance of ticagrelor 60mg twice daily is unclear. This study aimed to evaluate platelet inhibition of low-dose ticagrelor compared to prasugrel in Japanese patients.. A total of 33 patients with prior myocardial infarction (>3 months) who received aspirin and prasugrel 3.75mg once daily were enrolled. Prasugrel was switched to ticagrelor 60mg twice daily. Platelet inhibition was assessed by VerifyNow assay (Accumetrics, San Diego, CA, USA) at baseline and 14 days after switching to ticagrelor. P2Y12 reaction unit (PRU) ≤95 was defined as low on-treatment platelet reactivity (LPR) and PRU≥262 as high on-treatment platelet reactivity.. Ticagrelor treatment resulted in significantly lower PRU [10 (7-39) vs. 143 (102-201), p<0.001] and a higher rate of LPR (94% vs. 24%, p<0.001), compared to prasugrel treatment. Neither patients treated with ticagrelor nor prasugrel had high on-treatment platelet reactivity. During 2-week follow-up on ticagrelor therapy, no major bleeding occurred in both groups, while four minor bleeding events were observed.. In Japanese patients with prior myocardial infarction, significantly lower PRU and a higher rate of LPR were observed on ticagrelor 60mg twice daily compared to prasugrel 3.75mg once daily.

Topics: Aged; Asian People; Blood Platelets; Drug Substitution; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Ticagrelor

PEGASUS-TIMI 54 demonstrated that long-term dual antiplatelet therapy (DAPT) with aspirin and ticagrelor reduced the risk of major adverse cardiovascular events (MACE), with an acceptable increase in bleeding, in patients with prior myocardial infarction (MI). While much of the discussion around prolonged DAPT has been focused on stented patients, patients with prior MI without prior coronary stenting comprise a clinically important subgroup.. This was a pre-specified analysis from PEGASUS-TIMI 54, which randomized 21 162 patients with prior MI (1-3 years) and additional high-risk features to ticagrelor 60 mg, 90 mg, or placebo twice daily in addition to aspirin. A total of 4199 patients had no history of coronary stenting at baseline. The primary efficacy outcome (MACE) was the composite of cardiovascular death, MI, or stroke. Patients without history of coronary stenting had higher baseline risk of MACE [13.2% vs. 8.0%, adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.15-1.73, in the placebo arm]. The relative risk reduction in MACE with ticagrelor (pooled doses) was similar in patients without (HR 0.82, 95% CI 0.68-0.99) and with prior stenting (HR 0.85, 95% CI 0.75-0.96; P for interaction = 0.76).. Long-term ticagrelor reduces thrombotic events in patients with prior MI regardless of whether they had prior coronary stenting. These data highlight the benefits of DAPT in prevention of spontaneous atherothrombotic events and indicate that long-term ticagrelor may be considered in high-risk patients with prior MI even if they have not been treated with stenting.. NCT01225562.

Topics: Adenosine; Drug Therapy, Combination; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Ticagrelor; Treatment Outcome

Platelet P2Y12 antagonist ticagrelor reduces mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets, leukocytes, and endothelial cells release proinflammatory and prothrombotic extracellular vesicles (EVs), we hypothesized that the release of EVs is more efficiently inhibited by ticagrelor compared to clopidogrel.. We compared EV concentrations and EV procoagulant activity in plasma of patients after AMI treated with ticagrelor or clopidogrel.. After percutaneous coronary intervention, 60 patients with first AMI were randomized to ticagrelor or clopidogrel. Flow cytometry was used to determine concentrations of EVs from activated platelets (CD61. Concentrations of platelet, fibrinogen. Ticagrelor attenuates the increase of EV concentrations in plasma after acute myocardial infarction compared to clopidogrel. The ongoing release of EVs despite antiplatelet therapy might explain recurrent thrombotic events after AMI and worse clinical outcomes on clopidogrel compared to ticagrelor.

Topics: Clopidogrel; Endothelial Cells; Extracellular Vesicles; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

An estimated 15% of saphenous vein grafts (SVGs) occlude in the first year after coronary artery bypass grafting (CABG) despite aspirin therapy. Graft occlusion can result in symptoms, myocardial infarction, and death. SVG occlusion is primarily caused by atherothrombosis, in which platelet activation plays a pivotal role. Evidence regarding the effect of stronger platelet inhibition on SVG patency after CABG is limited. The main objective of the POPular CABG trial is to determine whether dual antiplatelet therapy with aspirin plus ticagrelor improves SVG patency when compared to aspirin alone.. The POPular CABG is a randomized, double-blind, placebo-controlled, multicenter trial investigating the effect of adding ticagrelor to standard aspirin therapy on the rate of SVG occlusion. A total of 500 patients undergoing CABG with ≥ 1 SVG are randomized to ticagrelor or placebo. The primary end point is SVG occlusion rate, assessed with coronary computed tomography angiography at 1 year. Secondary end points are stenoses and occlusions in both SVGs and arterial grafts and SVG failure at 1 year, defined as a composite of SVG occlusion on coronary computed tomography angiography or coronary angiography, SVG revascularization, myocardial infarction in the territory supplied by an SVG, or sudden death. Safety end points are bleeding events at 30 days and 1 year.. The POPular CABG trial investigates whether adding ticagrelor to standard aspirin after CABG reduces the rate of SVG occlusion at 1 year.

Topics: Aged; Aspirin; Computed Tomography Angiography; Coronary Angiography; Coronary Artery Bypass; Death, Sudden, Cardiac; Double-Blind Method; Drug Therapy, Combination; Graft Occlusion, Vascular; Humans; Myocardial Infarction; Placebos; Platelet Aggregation Inhibitors; Research Design; Sample Size; Saphenous Vein; Ticagrelor; Vascular Patency

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

Topics: Aged; Female; Humans; Male; Metoclopramide; Middle Aged; Morphine; Myocardial Infarction; Platelet Aggregation Inhibitors; Ticagrelor

Current guidelines recommend potent platelet inhibition with ticagrelor or prasugrel in patients after an acute coronary syndrome. However, data about optimal platelet inhibition in older patients are scarce. We aimed to investigate the safety and efficacy of clopidogrel compared with ticagrelor or prasugrel in older patients with non-ST-elevation acute coronary syndrome (NSTE-ACS).. We did the open-label, randomised controlled POPular AGE trial in 12 sites (ten hospitals and two university hospitals) in the Netherlands. Patients aged 70 years or older with NSTE-ACS were enrolled and randomly assigned in a 1:1 ratio using an internet-based randomisation procedure with block sizes of six to receive a loading dose of clopidogrel 300 mg or 600 mg, or ticagrelor 180 mg or prasugrel 60 mg, and then a maintenance dose for the duration of 12 months (clopidogrel 75 mg once daily, ticagrelor 90 mg twice daily, or prasugrel 10 mg once daily) on top of standard care. Patient and treating physicians were aware of the allocated treatment strategy, but the outcome assessors were masked to treatment allocation. Primary bleeding outcome consisted of PLATelet inhibition and patient Outcomes (PLATO; major or minor bleeding [superiority hypothesis]). Co-primary net clinical benefit outcome consisted of all-cause death, myocardial infarction, stroke, PLATO major and minor bleeding (non-inferiority hypothesis, margin of 2%). Follow-up duration was 12 months. Analyses were done on intention-to-treat basis. This trial is registered with the Netherlands Trial Register (NL3804), ClinicalTrials.gov (NCT02317198), and EudraCT (2013-001403-37).. Between June 10, 2013, and Oct 17, 2018, 1002 patients were randomly assigned to clopidogrel (n=500) or ticagrelor or prasugrel (n=502). Because 475 (95%) patients received ticagrelor in the ticagrelor or prasugrel group, we will refer to this group as the ticagrelor group. Premature discontinuation of the study drug occurred in 238 (47%) of 502 ticagrelor group patients randomly assigned to ticagrelor, and in 112 (22%) of 500 patients randomly assigned to clopidogrel. Primary bleeding outcome was significantly lower in the clopidogrel group (88 [18%] of 500 patients) than in the ticagrelor group (118 [24%] of 502; hazard ratio 0·71, 95% CI 0·54 to 0·94; p=0·02 for superiority). Co-primary net clinical benefit outcome was non-inferior for the use of clopidogrel (139 [28%]) versus ticagrelor (161 [32%]; absolute risk difference -4%, 95% CI -10·0 to 1·4; p=0·03 for non-inferiority). The most important reasons for discontinuation were occurrence of bleeding (n=38), dyspnoea (n=40), and the need for treatment with oral anticoagulation (n=35).. In patients aged 70 years or older presenting with NSTE-ACS, clopidogrel is a favourable alternative to ticagrelor, because it leads to fewer bleeding events without an increase in the combined endpoint of all-cause death, myocardial infarction, stroke, and bleeding. Clopidogrel could be an alternative P2Y12 inhibitor especially for elderly patients with a higher bleeding risk.. ZonMw.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Clopidogrel; Female; Humans; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Stroke; Ticagrelor

Topics: Aged; Aspirin; Beverages; Caffeine; Double-Blind Method; Dual Anti-Platelet Therapy; Dyspnea; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Prospective Studies; Recurrence; Risk Assessment; Risk Factors; Secondary Prevention; Ticagrelor; Time Factors; Treatment Outcome

Oral P2Y. This study sought to assess inhibition of platelet aggregation following subcutaneous administration of selatogrel in patients with AMI.. Patients with AMI were randomized to a single subcutaneous dose of selatogrel of 8 or 16 mg. The primary endpoint was response to treatment (P2Y. Forty-seven patients received selatogrel 8 mg (n = 24) or 16 mg (n = 23) followed by ticagrelor (n = 43) or clopidogrel (n = 1). The proportion of responders 30 min post-dose was 91% (one-sided 97.5% confidence interval [CI]: 80% to 100%) and 96% (97.5% CI: 87% to 100%) with 8 and 16 mg, respectively (p values for responders >85% target; p = 0.142 and p = 0.009, respectively). Response rates were independent from type of AMI presentation, age, or sex. A similar response rate was observed at 15 min (8 mg: 75% [97.5% CI: 58% to 100%]; 16 mg: 91% [97.5% CI: 80% to 100%]), which was sustained at 60 min post-dose (8 mg: 75% [97.5% CI: 58% to 100%]; 16 mg: 96% [97.5% CI: 87% to 100%]). At 15 min, median P2Y. Single-dose subcutaneous administration of selatogrel in patients with AMI was safe and induced a profound, rapid, and dose-related antiplatelet response. (A Medical Research Study to Evaluate the Effects of ACT-246475 in Adults With Heart Attack; NCT03487445, 2018-000765-36 [EudraCT]).

Topics: Adult; Aged; Aged, 80 and over; Body Weight; Clopidogrel; Drug Therapy, Combination; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Myocardial Infarction; Organophosphonates; Patient Safety; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Pyrimidines; Ticagrelor; Treatment Outcome

Topics: Acute Coronary Syndrome; Aged; Atherosclerosis; Case-Control Studies; Clopidogrel; Cysteine Endopeptidases; Cysteine Proteases; Death; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Risk Factors; Stroke; Ticagrelor; Treatment Outcome

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

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

Topics: Aged; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Humans; Male; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Stroke; 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

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

Q-wave myocardial infarction (QWMI) comprises 2 entities. First, a clinically evident MI, which can occur spontaneously or be related to a coronary procedure. Second, silent MI which is incidentally detected on serial electrocardiographic (ECG) assessment. The prevalence of silent MI after percutaneous coronary intervention (PCI) in the drug-eluting stent era has not been fully investigated. The GLOBAL LEADERS is an all-comers multicenter trial which randomized 15,991 patients who underwent PCI to 2 antiplatelet treatment strategies. The primary end point was a composite of all-cause death or nonfatal new QWMI at 2-years follow-up. ECGs were collected at discharge, 3-month and 2-year visits, and analyzed by an independent ECG core laboratory following the Minnesota code. All new QWMI were further reviewed by a blinded independent cardiologist to identify a potential clinical correlate by reviewing clinical information. Of 15,968 participants, ECG information was complete in 14,829 (92.9%) at 2 years. A new QWMI was confirmed in 186 (1.16%) patients. Transient new Q-waves were observed in 28.5% (53 of 186) of them during the follow-up. The majority of new QWMI (78%, 146 of 186) were classified as silent MI due to the absence of a clinical correlate. Silent MI accounted for 22.1% (146 of 660) of all MI events. The prevalence of silent MI did not differ significantly between treatment strategies (experimental vs reference: 0.88% vs 0.98%, p = 0.5027). In conclusion, we document the prevalence of silent MI in an all-comers population undergoing PCI in this large-scale randomized trial.

Topics: Aged; Analysis of Variance; Aspirin; Asymptomatic Diseases; Coronary Angiography; Drug Therapy, Combination; Drug-Eluting Stents; Electrocardiography; Female; Humans; Internationality; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Prognosis; Prospective Studies; Risk Assessment; Statistics, Nonparametric; Survival Analysis; Ticagrelor; Treatment Outcome

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

Patients with peripheral artery disease (PAD) are at high risk for myocardial infarction (MI).. To characterize the incidence and types of MI in a PAD population, identify factors associated with MI, and determine the association of MI with cardiovascular mortality and acute limb ischemia.. The Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease (EUCLID) was a double-blind randomized clinical trial conducted at 811 sites in 28 countries that randomized 13 885 patients with symptomatic PAD to monotherapy with ticagrelor or clopidogrel. Participants had an ankle-brachial index (ABI) of 0.80 or less or previous lower extremity revascularization. Median follow-up was 30 months. For these analyses, patients were evaluated for MI occurrence during follow-up irrespective of treatment. Data were analyzed from June 2017 to September 2018.. An adjudication clinical events committee classified MI as type 1 (spontaneous), type 2 (secondary), type 3 (sudden cardiac death), type 4a (less than 48 hours after percutaneous coronary intervention), type 4b (definite stent thrombosis), or type 5 (less than 72 hours after coronary artery bypass graft). A multivariate regression model was developed by stepwise selection to identify factors associated with MI, and a time-dependent multivariate Cox regression analysis was performed to determine the association of MI with cardiovascular death and acute limb ischemia requiring hospitalization.. Of the 13 885 patients included in this analysis, 9997 (72.0%) were male, and the median (interquartile range) age was 66 (60-73) years. Myocardial infarction occurred in 683 patients (4.9%; 2.4 events per 100 patient-years) during a median follow-up of 30 months. Patients experiencing MI were older (median [interquartile range] age, 69 [62-75] vs 66 [60-72] years), more likely to have diabetes (349 of 683 [51.1%] vs 4996 of 13 202 [37.8%]) or a previous lower extremity revascularization (466 of 683 [68.2%] vs 7409 of 13 202 [56.1%]), and had a lower ABI (if included by ABI) compared with censored patients. Of the 683 patients with MI during follow-up, the most common MI type was type 1 (405 [59.3%]), followed by type 2 (236 [34.6%]), type 4a (14 [2.0%]), type 3 (12 [1.8%]), type 4b (11 [1.6%]), and type 5 (5 [0.7%]). Postrandomization MI was independently associated with cardiovascular death (adjusted hazard ratio, 9.0; 95% CI, 7.3-11.2; P < .001) and acute limb ischemia requiring hospitalization (adjusted hazard ratio, 2.5; 95% CI, 1.3-5.0; P = .008).. Approximately 5% of patients with symptomatic PAD had an MI during a median follow-up of 30 months. Type 1 MI (spontaneous) was the most common MI type; however, one-third of MIs were type 2 MI (secondary). More research is needed to identify therapies to reduce the risk of MI in patients with PAD and to improve management of type 2 MI.. ClinicalTrials.gov Identifier: NCT01732822.

Topics: Aged; Ankle Brachial Index; Clopidogrel; Coronary Artery Bypass; Death; Extremities; Female; Hospitalization; Humans; Incidence; Ischemia; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor

Despite guideline recommendations, many patients discontinue P2Y12 inhibitor therapy earlier than the recommended 1 year after myocardial infarction (MI), and higher-potency P2Y12 inhibitors are underutilized. Cost is frequently cited as an explanation for both of these observations.. To determine whether removing co-payment barriers increases P2Y12 inhibitor persistence and lowers risk of major adverse cardiovascular events (MACE).. Cluster randomized clinical trial among 301 hospitals enrolling adult patients with acute MI (June 5, 2015, through September 30, 2016); patients were followed up for 1 year after discharge (final date of follow-up was October 23, 2017), with blinded adjudication of MACE; choice of P2Y12 inhibitor was per clinician discretion.. Hospitals randomized to the intervention (n = 131 [6436 patients]) provided patients with co-payment vouchers for clopidogrel or ticagrelor for 1 year (median voucher value for a 30-day supply, $137 [25th-75th percentile, $20-$339]). Hospitals randomized to usual care (n = 156 [4565 patients]) did not provide study vouchers.. Independent coprimary outcomes were patient-reported persistence with P2Y12 inhibitor (defined as continued treatment without gap in use ≥30 days) and MACE (death, recurrent MI, or stroke) at 1 year among patients discharged with a prescription for clopidogrel or ticagrelor.. Among 11 001 enrolled patients (median age, 62 years; 3459 [31%] women), 10 102 patients were discharged with prescriptions for clopidogrel or ticagrelor (clopidogrel prescribed to 2317 [36.0%] in the intervention group and 2497 [54.7%] in the usual care group), 4393 of 6135 patients (72%) in the intervention group used the voucher, and follow-up data at 1 year were available for 10 802 patients (98.2%). Patient-reported persistence with P2Y12 inhibitors at 1 year was higher in the intervention group than in the control group (unadjusted rates, 5340/6135 [87.0%] vs 3324/3967 [83.8%], respectively; P < .001; adjusted difference, 2.3% [95% CI, 0.4% to 4.1%]; adjusted odds ratio, 1.19 [95% CI, 1.02 to 1.40]). There was no significant difference in MACE at 1 year between intervention and usual care groups (unadjusted cumulative incidence, 10.2% vs 10.6%; P = .65; adjusted difference, 0.66% [95% CI, -0.73% to 2.06%]; adjusted hazard ratio, 1.07 [95% CI, 0.93 to 1.25]).. Among patients with MI, provision of vouchers to offset medication co-payments for P2Y12 inhibitors, compared with no vouchers, resulted in a 3.3% absolute increase in patient-reported persistence with P2Y12 inhibitors and no significant reduction in 1-year MACE outcomes.. ClinicalTrials.gov Identifier: NCT02406677.

Topics: Aged; Clopidogrel; Cost Sharing; Drug Costs; Female; Humans; Male; Medication Adherence; Middle Aged; Myocardial Infarction; Odds Ratio; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Recurrence; Stroke; 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

In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients ≥50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of ≥50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.

Topics: Aged; Aspirin; Clinical Trials, Phase III as Topic; Coronary Artery Disease; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Ticagrelor; Time Factors; Treatment Outcome

The GLOBAL LEADERS is an open-label, pragmatic and superiority randomised controlled trial designed to challenge the current treatment paradigm of dual antiplatelet therapy (DAPT) for 12 months followed by aspirin monotherapy among patients undergoing percutaneous coronary intervention. By design, all study endpoints are investigator reported (IR) and not subject to formal adjudication by an independent Clinical Event Committee (CEC), which may introduce detection, reporting or ascertainment bias.. We designed the GLOBAL LEADERS Adjudication Sub-StudY (GLASSY) to prospectively implement, in a large sample of patients enrolled within the GLOBAL LEADERS trial (7585 of 15 991, 47.5%), an independent adjudication process of reported and unreported potential endpoints, using standardised CEC procedures, in order to assess whether 23-month ticagrelor monotherapy (90 mg twice daily) after 1-month DAPT is non-inferior to a standard regimen of DAPT for 12 months followed by aspirin monotherapy for the primary efficacy endpoint of death, non-fatal myocardial infarction, non-fatal stroke or urgent target vessel revascularisation and superior for the primary safety endpoint of type 3 or 5 bleeding according to the Bleeding Academic Research Consortium criteria.This study will comprehensively assess the comparative safety and efficacy of the two tested antithrombotic strategies on CEC-adjudicated ischaemic and bleeding endpoints and will provide insights into the role of a standardised CEC adjudication process on the interpretation of study findings by quantifying the level of concordance between IR-reported and CEC-adjudicated events.. GLASSY has been approved by local ethics committee of all study sites and/or by the central ethics committee for the country depending on country-specific regulations. In all cases, they deemed that it was not necessary to obtain further informed consent from individual subjects.. NCT01813435.

Topics: Aspirin; Coronary Artery Disease; Drug Administration Routes; Drug Therapy, Combination; Endpoint Determination; Humans; Myocardial Infarction; Myocardial Revascularization; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Research Design; Stroke; Ticagrelor

Previous ischemic stroke is a predictor of recurrent ischemic stroke after an acute myocardial infarction (AMI). Dual antiplatelet therapy, including a P2Y12-inhibitor, is important in secondary prevention after AMI. Ticagrelor, a P2Y12-inhibitor, is more potent than the commonly used clopidogrel. Here, we evaluated the impact of ticagrelor on the risk of ischemic stroke following AMI in patients with previous ischemic stroke.. Data for patients with AMI that had a previous ischemic stroke were obtained from the Swedish Registry of Information and Knowledge about Swedish Heart Intensive Care Admissions. Patients were assigned to early and late cohorts, each covering a two-year time period before and after, respectively, the introduction of ticagrelor prescriptions (20 Dec 2011). Patients in the early cohort (n = 1633) were treated with clopidogrel (100%); those in the late cohort (n = 1642) were treated with either clopidogrel (66.3%) or ticagrelor (33.7%). We assessed the risk of ischemic stroke and intracranial bleeding over time with Kaplan-Meier analyses. We identified predictors of ischemic stroke with multivariable Cox regression analyses.. Of 3275 patients, 311 experienced ischemic stroke after AMI. Cumulative Kaplan-Meier incidence estimates of ischemic stroke within one year after AMI were 12.1% versus 8.6% for the early and late cohorts, respectively (p<0.01). Intracranial bleeding incidences (1.2% versus 1.5%) were similar between the two cohorts.. Ticagrelor introduction was associated with a lower rate of ischemic stroke, with no increase in intracranial bleeding, in an AMI population with a history of ischemic stroke.

Topics: Aged; Aged, 80 and over; Brain Ischemia; Clopidogrel; Disease-Free Survival; Female; Humans; Male; Myocardial Infarction; Registries; Risk Factors; Stroke; Survival Rate; Ticagrelor

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

 Oral P2Y12 inhibitors take more than 2 hours to achieve full effect in healthy subjects and this action is further delayed in patients with acute myocardial infarction. Intravenous P2Y12 inhibition might lead to more timely and potent anti-platelet effect in the context of emergency primary angioplasty, improving myocardial recovery..  This article compares the efficacy of intravenous cangrelor versus ticagrelor in a ST-elevation myocardial infarction (STEMI) population treated with primary percutaneous coronary intervention (PPCI)..  In an open-label, prospective, randomized controlled trial, 100 subjects with STEMI were assigned 1:1 to intravenous cangrelor or oral ticagrelor. The co-primary endpoints were platelet P2Y12 inhibition at infarct vessel balloon inflation time, 4 and 24 hours. Secondary endpoints included indices of coronary microcirculatory function: index of microvascular resistance (IMR), initial infarct size (troponin at 24 hours) and final infarct size at 12 weeks (cardiac magnetic resonance). Secondary endpoints included indices of coronary microcirculatory function (index of microvascular resistance [IMR]), initial infarct size (troponin at 24 hours), final infarct size at 12 weeks (cardiac magnetic resonance), corrected thrombolysis in myocardial infarction (TIMI) frame count, TIMI flow grade, myocardial perfusion grade, and ST-segment resolution (ClinicalTrials.gov NCT02733341)..  P2Y12 inhibition at first balloon inflation time was significantly greater in cangrelor-treated patients (cangrelor P2Y12 reaction unit [PRU] 145.2 ± 50.6 vs. ticagrelor 248.3 ± 55.1). There was no difference in mean PRU at 4 and 24 to 36 hours post-dosing. IMR, final infarct size, angiographic and electrocardiographic measures of reperfusion were all similar between groups..  Cangrelor produces more potent P2Y12 inhibition at the time of first coronary balloon inflation time compared with ticagrelor. Despite this enhanced P2Y12 inhibition, coronary microvascular function and final infarct size did not differ between groups.

Topics: Adenosine Monophosphate; Aged; Blood Platelets; Blood Vessels; Cells, Cultured; Female; Humans; Male; Microcirculation; Middle Aged; Myocardial Infarction; Myocardium; Percutaneous Coronary Intervention; Platelet Activation; Platelet Function Tests; Receptors, Purinergic P2Y12; Regional Blood Flow; Ticagrelor

The degree and time course of platelet inhibition using ticagrelor can vary during the acute phase and the following stable period after acute myocardial infarction (AMI). The optimal level of platelet inhibition during the various stages of AMI remains an open question. The aim of the current study is to compare the antiplatelet efficacy of two ticagrelor maintenance dose regimens (60 mg b.i.d. vs. 90 mg b.i.d.) in stable patients following an initial strategy with ticagrelor 90 mg b.i.d. during the first month after AMI.. The Effectiveness of LowEr maintenanCe dose of TicagRelor early After myocardial infarction (ELECTRA) pilot study is a phase III, single-centre, randomized, open-label, pharmacokinetic/pharmacodynamic trial. The study population will include 50 patients with AMI treated with percutaneous coronary intervention. At Day 30 post-AMI, all trial participants will be randomly assigned in 1:1 ratio to receive either reduced (60 mg b.i.d.) or standard (90 mg b.i.d.) maintenance ticagrelor dose until Day 45 post-AMI. Platelet function testing in each patient will be performed using up to two different methods (the VASP assay and multiple electrode aggregometry). Pharmacokinetics of ticagrelor and its active metabolite (AR-C124910XX) will be assessed by liquid chromatography mass spectrometry.. A de-escalation strategy with reduced dose of ticagrelor (60 mg b.i.d.) following an initial standard dose (90 mg b.i.d.) during the first month after AMI may provide equally effective platelet inhibition as compared to maintenance with the standard ticagrelor dose.. NCT03251859.

Topics: Biomarkers; Blood Platelets; Cell Adhesion Molecules; Chromatography, Liquid; Clinical Trials, Phase III as Topic; Drug Monitoring; Humans; Mass Spectrometry; Microfilament Proteins; Myocardial Infarction; Percutaneous Coronary Intervention; Phosphoproteins; Pilot Projects; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Poland; Randomized Controlled Trials as Topic; Ticagrelor; Treatment Outcome

Observational studies suggest that symptomatic atherosclerosis may be associated with risk of venous thromboembolism (VTE). Prior randomized studies have demonstrated a significant reduction in recurrent VTE with aspirin monotherapy. Whether VTE risk is associated with more severe symptomatic atherosclerosis and more intensive antiplatelet therapy reduces VTE risk beyond aspirin monotherapy is unknown.. TRA2P-TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction) (vorapaxar) and 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) (ticagrelor) were blinded, randomized placebo-controlled trials of antiplatelet therapy for the prevention of ischemic events in stable patients with symptomatic atherosclerosis. Two blinded vascular specialists systematically identified symptomatic venous thromboembolic events in both trials.. The rate of VTE in patients with atherosclerosis is ≈0.3% per year while on treatment with ≥1 antiplatelet agent, with increased risk independently associated with the number of symptomatic vascular territories. More intensive antiplatelet therapy reduces the risk of VTE. These data suggest a relationship between atherosclerosis burden and VTE risk, and they support inclusion of VTE as a prospective end point in long-term secondary prevention trials evaluating the risks and benefits of antiplatelet therapies in patients with atherosclerosis.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01225562.

Topics: Aged; Aspirin; Atherosclerosis; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor; Venous Thromboembolism

Early outcomes of patients in the PRAGUE-18 (Comparison of Prasugrel and Ticagrelor in the Treatment of Acute Myocardial Infarction) study did not find any significant differences between 2 potent P2Y. The 1-year follow-up of the PRAGUE-18 study focused on: 1) a comparison of efficacy and safety between prasugrel and ticagrelor; and 2) the risk of major ischemic events related to an economically motivated post-discharge switch to clopidogrel.. A total of 1,230 patients with acute myocardial infarction (MI) treated with primary percutaneous coronary intervention were randomized to prasugrel or ticagrelor with an intended treatment duration of 12 months. The combined endpoint was cardiovascular death, MI, or stroke at 1 year. Because patients had to cover the costs of study medication after hospital discharge, some patients decided to switch to clopidogrel.. The endpoint occurred in 6.6% of prasugrel patients and in 5.7% of ticagrelor patients (hazard ratio: 1.167; 95% confidence interval: 0.742 to 1.835; p = 0.503). No significant differences were found in: cardiovascular death (3.3% vs. 3.0%; p = 0.769), MI (3.0% vs. 2.5%; p = 0.611), stroke (1.1% vs. 0.7%; p = 0.423), all-cause death (4.7% vs. 4.2%; p = 0.654), definite stent thrombosis (1.1% vs. 1.5%; p = 0.535), all bleeding (10.9% vs. 11.1%; p = 0.999), and TIMI (Thrombolysis In Myocardial Infarction) major bleeding (0.9% vs. 0.7%; p = 0.754). The percentage of patients who switched to clopidogrel for economic reasons was 34.1% (n = 216) for prasugrel and 44.4% (n = 265) for ticagrelor (p = 0.003). Patients who were economically motivated to switch to clopidogrel had (compared with patients who continued the study medications) a lower risk of major cardiovascular events; however, they also had lower ischemic risk.. Prasugrel and ticagrelor are similarly effective during the first year after MI. Economically motivated early post-discharge switches to clopidogrel were not associated with an increased risk of ischemic events. (Comparison of Prasugrel and Ticagrelor in the Treatment of Acute Myocardial Infarction [PRAGUE-18]; NCT02808767).

Topics: Aged; Clopidogrel; Follow-Up Studies; Humans; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor; Time Factors; Treatment Outcome

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

Patients with prior myocardial infarction (MI) and multivessel coronary disease (MVD) are at high risk for recurrent coronary events.. The authors investigated the efficacy and safety of ticagrelor versus placebo in patients with MVD 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.. Patients with a history of MI 1 to 3 years before inclusion in the PEGASUS-TIMI 54 trial were stratified in a pre-specified analysis based on the presence of MVD. The effect of ticagrelor (60 mg and 90 mg) on the composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events [MACE]), as well as the composite of coronary death, MI, or stent thrombosis (coronary events), and on TIMI major bleeding, intracranial hemorrhage (ICH), and fatal bleeding were evaluated over a median of 33 months.. A total of 12,558 patients (59.4%) had MVD. In the placebo arm, compared with patients without MVD, those with MVD were at higher risk for MACE (9.37% vs. 8.57%, adjusted hazard ratio [HR. Patients with prior MI and MVD are at increased risk of MACE and coronary events, and experience substantial relative and absolute risk reductions in both outcomes with long-term ticagrelor treatment relative to those without MVD. Ticagrelor increases the risk of TIMI major bleeding, but not ICH or fatal bleeding. For patients with prior MI and MVD, ticagrelor is an effective option for long-term antiplatelet therapy. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).

Topics: Aged; Coronary Artery Disease; Drug Administration Schedule; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Secondary Prevention; Stroke; Thrombosis; Ticagrelor

Topics: Aged; Blood Platelets; Clopidogrel; Female; Humans; Ischemia; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Stents; Thrombosis; Ticagrelor; Time Factors; 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

This study aimed to compare the effects of ticagrelor and clopidogrel on early neointimal healing assessed with optical coherence tomography (OCT) after drug-eluting stent (DES) implantation in patients with acute myocardial infarction (AMI).. AMI patients were randomly assigned to either the ticagrelor or clopidogrel arm. After DES implantation, OCT was performed to assess the percentages of uncovered struts immediately after procedure and 3 months later.. Due to early termination, 83 patients out of 106 initially enrolled patients (24% of planned participants) underwent 3-month OCT. Differences in vascular healing patterns between the two groups, including percentage of uncovered struts on 3-month OCT (9.6% vs. 11.7% in ticagrelor vs. clopidogrel, respectively; p=0.867), neointimal thickness, percentage of malapposed struts, and healing scores did not reach statistical significance. The predictors of uncovered strut on 3-month OCT included greater reference vessel diameter [odds ratio (OR)=1.96, p<0.001] and more malapposed struts (OR=1.12, p=0.003).. The current study did not explore favorable effect of ticagrelor on 3-month vascular healing after DES implantation. Our findings should only be considered for generating hypothesis, due to insufficient power.

Topics: Adenosine; Aged; Clopidogrel; Coronary Angiography; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Neointima; Prospective Studies; Prostheses and Implants; Ticagrelor; Ticlopidine; Tomography, Optical Coherence; Treatment Outcome

Patients with peripheral artery disease (PAD) are at heightened risk of cardiovascular morbidity and mortality. We sought to evaluate the risk of concomitant coronary artery disease (CAD) in patients with symptomatic PAD versus PAD without diagnosed CAD, and whether ticagrelor was superior to clopidogrel in reducing that risk. The EUCLID trial randomized 13,885 patients with PAD to antithrombotic monotherapy with ticagrelor or clopidogrel. CAD was defined as prior myocardial infarction (MI), percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG) surgery. Median follow-up was 30 months. Among 4032 (29%) patients with PAD and CAD, 63% had prior MI, 54% prior PCI, and 38% prior CABG. After adjustment for baseline characteristics, patients with PAD and CAD had significantly higher rates of the primary endpoint (cardiovascular death/MI/stroke, 15.3% vs 8.9%, hazard ratio (HR) 1.50, 95% CI: 1.13-1.99; p=0.005), but no statistically significant increase in acute limb ischemia (HR 1.28, 95% CI: 0.57-2.85; p=0.55) or major bleeding (HR 1.10, 95% CI: 0.49-2.48; p=0.81) versus PAD without CAD. Among patients with PAD and CAD, there was no differential treatment effect between ticagrelor versus clopidogrel for the primary efficacy endpoint (HR 1.02, 95% CI: 0.87-1.19; p=0.84), acute limb ischemia (HR 1.03, 95% CI: 0.63-1.69; p=0.89), or major bleeding (HR 1.06, 95% CI: 0.66-1.69; p=0.81). There was a statistically significant interaction between prior coronary stent placement and study treatment ( p=0.03) with a numerical reduction in the primary efficacy endpoint with ticagrelor versus clopidogrel (13.8% vs 16.8%, HR 0.82, 95% CI: 0.65-1.03; p=0.09). Patients with PAD and prior CAD had higher composite rates of cardiovascular death, MI, and ischemic stroke versus PAD without diagnosed CAD. There were no significant differences between ticagrelor and clopidogrel in cardiovascular events or major bleeding. ClinicalTrials.gov Identifier: NCT01732822.

Topics: Aged; Clopidogrel; Coronary Artery Bypass; Coronary Artery Disease; Double-Blind Method; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors; Stents; Stroke; Ticagrelor; Time Factors; Treatment Outcome

We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens.. GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75-100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75-100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with follow-up completed.. Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3·81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4·37%) participants in the control group (rate ratio 0·87 [95% CI 0·75-1·01]; p=0·073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0·93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2·04% vs 2·12%; rate ratio 0·97 [95% CI 0·78-1·20]; p=0·77).. Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention.. AstraZeneca, Biosensors, and The Medicines Company.

Topics: Adenosine; Aged; Aspirin; Clopidogrel; Coronary Angiography; Coronary Artery Disease; Drug Therapy, Combination; Drug-Eluting Stents; Female; Humans; Intention to Treat Analysis; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine

Background Ticagrelor reduced cardiovascular death, myocardial infarction (MI), or stroke in patients with prior MI in PEGASUS-TIMI 54 (Prevention of Cardiovascular Events [eg, Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin). MI can occur in diverse settings and with varying severity; therefore, understanding the types and sizes of MI events prevented is of clinical importance. Methods and Results MIs were adjudicated by a blinded clinical events committee and categorized by subtype and fold elevation of peak cardiac troponin over the upper limit of normal. A total of 1042 MIs occurred in 898 of the 21 162 randomized patients over a median follow-up of 33 months. The majority of the MIs (76%) were spontaneous (Type 1), with demand MI (Type 2) and stent thrombosis (Type 4b) accounting for 13% and 9%, respectively; sudden death (Type 3), percutaneous coronary intervention-related (Type 4a) and coronary artery bypass graft-related (Type 5) each accounted for <1%. Half of MIs (520, 50%) had a peak troponin ≥10x upper limit of normal and 21% of MIs (220) had a peak troponin ≥100× upper limit of normal. A total of 21% (224) were ST-segment-elevation MI STEMI. Overall ticagrelor reduced MI (4.47% versus 5.25%, hazard ratio 0.83, 95% confidence interval 0.72-0.95, P=0.0055). The benefit was consistent among the subtypes, including a 31% reduction in MIs with a peak troponin ≥100× upper limit of normal (hazard ratio 0.69, 95% confidence interval 0.53-0.92, P=0.0096) and a 40% reduction in ST-segment elevation MI (hazard ratio 0.60, 95% confidence interval 0.46-0.78, P=0.0002). Conclusions In stable outpatients with prior MI, the majority of recurrent MIs are spontaneous and associated with a high biomarker elevation. Ticagrelor reduces the MI consistently among subtypes and sizes including large MIs and ST-segment elevation MI. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01225562.

Topics: Aged; Death, Sudden, Cardiac; Humans; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Ticagrelor

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

The most common classification of acute myocardial infarction (AMI) is based on electrocardiographic findings and distinguishes ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). Both types of AMI differ concerning their epidemiology, clinical approach and early outcomes. Ticagrelor is a P2Y12 receptor inhibitor, constituting the first-line treatment for STEMI and NSTEMI. According to available data, STEMI may be associated with lower plasma concentration of ticagrelor in the first hours of AMI, but currently there are no studies directly comparing ticagrelor pharmacokinetics or antiplatelet effect in patients with STEMI versus NSTEMI.. The PINPOINT study is a phase IV, single-centre, investigator-initiated, prospective, observational study designed to compare the pharmacokinetics and pharmacodynamics of ticagrelor in patients with STEMI and NSTEMI assigned to the invasive strategy of treatment. Based on an internal pilot study, the trial is expected to include at least 23 patients with each AMI type. All subjects will receive a 180 mg loading dose of ticagrelor. The primary end point of the study is the area under the plasma concentration-time curve (AUC. The study received approval from the Local Ethics Committee (Komisja Bioetyczna Uniwersytetu Mikołaja Kopernika w Toruniu przy Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy; approval reference number KB 617/2015). The study results will be disseminated through conference presentations and peer-reviewed journals.. NCT02602444; Pre-results.

Topics: Adenosine; Aged; Area Under Curve; Female; Humans; Male; Middle Aged; Myocardial Infarction; Pilot Projects; Prospective Studies; Purinergic P2Y Receptor Antagonists; Ticagrelor

Trimetazidine (TMZ) improves clinical outcomes in patients with chronic heart failure and stable coronary artery disease. No study has yet evaluated the efficacy of TMZ in type 2 diabetes patients with acute myocardial infarction (AMI) undergoing Percutaneous Coronary Intervention (PCI). We performed this study to evaluate the efficacy TMZ in DM patients with AMI undergoing PCI, such as the effect on reductions in myocardial enzyme, improvements in liver function, modulation of glucose levels, and improvement in cardiac function.. For this randomized study, we enrolled 173 AMI patients with type 2 diabetes undergoing PCI between January 1, 2014, and January 1, 2016. All patients received aspirin and ticagrelor upon admission and throughout their hospitalization. Patients in the experimental group were treated with a loading dose of 60mg TMZ at admission, and 20 mg TMZ three times a day thereafter. 89 patients were included in experimental group, and 84 patients were included in control group. All patients received PCI treatments. The endpoints evaluated were serum creatine kinase and its isoenzyme (CK and CK-MB), cardiac troponin I (cTNI), serum creatinine (Cr), serum urea, blood glucose, serum glutamic pyruvic transaminase (ALT), serum glutamic oxaloacetictransaminase (AST), left atrial dimension (LA), left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), and cardiac output (CO).. Compared with the control group, TMZ treatment significantly reduced CK and CK-MB on the second day in hospital ([797±582] vs. [1092±1114]; [80±60] vs. [105±100]; p=0.029, p=0.041, respectively), and cTNI after one and six days in hospital ([13.5±12.7] vs. [19.8±19.2]; [3.3±3.2] vs. [4.8±4.7]; two-tailed p=0.012). In addition, TMZ significantly lowered liver enzymes (ALT, AST) at 6days ([29.0±11.6] vs. [42.4±24.5]; [39.8±17.3] vs. [69.2±70.0]; two-tailed p=0.000), lowered glucose after 6days ([6.80±2.12] vs. [7.59±2.24]; p=0.019), and increased LVEF after ten to fourteen days ([58.4±8.6] vs. [54.9±8.4]; p=0.008). There were no significant effect on Cr and serum urea (p=0.988, p=0.569, respectively), nor on LA, LVEDD, and CO ([36.3±4.5] vs. [37.0±4.1], p=0.264; [52.0±4.9] vs. [53.1±4.6], p=0.128; [5.4±0.9] vs. [5.4±0.9], p=0.929, respectively).. Among type 2 diabetic patients with AMI undergoing PCI, TMZ significantly reduces serum myocardial enzyme, improves liver function, adjusts blood glucose and improves cardiac function.

Topics: Adenosine; Aged; Alanine Transaminase; Aspartate Aminotransferases; Aspirin; Blood Glucose; Cardiac Output; China; Creatine Kinase; Creatine Kinase, MB Form; Creatinine; Diabetes Mellitus, Type 2; Echocardiography; Female; Glycated Hemoglobin; Heart Atria; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Stroke Volume; Ticagrelor; Treatment Outcome; Trimetazidine; Troponin I; Urea; Vasodilator Agents

Ticagrelor is an effective antiplatelet therapy among patients with atherosclerotic disease and, therefore, could be more effective than aspirin in preventing recurrent stroke and cardiovascular events among patients with embolic stroke of unknown source (ESUS), which includes patients with ipsilateral stenosis <50% and aortic arch atherosclerosis.. We randomized 13 199 patients with a noncardioembolic, nonsevere ischemic stroke or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90) within 24 hours of symptom onset. In all patients, investigators informed on the presence of ipsilateral stenosis ≥50%, small deep infarct <15 mm, and on cardiac source of embolism detected after enrollment or rare causes, which allowed to construct an ESUS category in all other patients with documented brain infarction. The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.. In this post hoc, exploratory analysis, we found no treatment-by-ESUS category interaction. ESUS subgroups have heterogeneous response to treatment (Funded by AstraZeneca).. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.

Topics: Adenosine; Aged; Aortic Diseases; Aspirin; Atherosclerosis; Carotid Stenosis; Female; Humans; Intracranial Embolism; Ischemic Attack, Transient; Male; Middle Aged; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Recurrence; Stroke; Ticagrelor; Treatment Outcome

In patients with a myocardial infarction (MI) 1 to 3 years earlier, treatment with ticagrelor + low-dose aspirin (ASA) reduces the risk of cardiovascular (CV) death, MI, or stroke compared with low-dose aspirin alone, but at an increased risk of major bleeding.. The authors evaluated cost-effectiveness of ticagrelor + low-dose ASA in patients with prior MI within the prior 3 years.. The authors performed a prospective economic substudy alongside 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, which randomized 21,162 patients to ASA alone, ticagrelor 60 mg twice daily + low-dose ASA, or ticagrelor 90 mg twice daily + low-dose ASA. Medical resource use data were collected over a median 33-month follow-up. Costs were assessed from the U.S. health care system perspective. In-trial data relating to survival, utility, and costs were combined with lifetime projections to evaluate lifetime cost-effectiveness of the Food and Drug Administration-approved lower-dose ticagrelor regimen (60 mg twice daily).. Hospitalization costs were similar for ticagrelor 60 mg and placebo ($2,262 vs. $2,333; 95% confidence interval for difference -$303 to $163; p = 0.54); after inclusion of a daily ticagrelor 60 mg cost of $10.52, total costs were higher for ticagrelor ($10,016 vs. $2,333; 95% CI: $7,441 to $7,930; p < 0.001). In-trial quality-adjusted life-years (QALYs) were similar (2.28 vs. 2.27; p = 0.34). Over a lifetime horizon, ticagrelor was associated with QALY gains of 0.078 and incremental costs of $7,435, yielding an incremental cost-effectiveness ratio (ICER) of $94,917/QALY gained. Several high-risk groups had more favorable ICERs, including patients with >1 prior MI, multivessel disease, diabetes, renal dysfunction (all with ICERs $50,000 to $70,000/QALY gained), patients age <75 years (ICER = $44,779/QALY gained), and patients with peripheral artery disease (ICER = $13,427/QALY gained).. For patients with a history of MI >1 year previously, long-term treatment with ticagrelor 60 mg + low-dose ASA yields a cost-effectiveness ratio suggesting intermediate value based on current guidelines. Ticagrelor appears to provide higher value for patients in several recognized high-risk subgroups. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).

Topics: Adenosine; Aged; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Myocardial Infarction; Prospective Studies; Purinergic P2Y Receptor Antagonists; Recurrence; Secondary Prevention; Stroke; Ticagrelor; Time Factors

Ticagrelor reduces ischemic risk in patients with prior myocardial infarction (MI). It remains unclear whether ischemic risk and the benefits of prolonged P2Y. The study sought to investigate the pattern of ischemic risk over time and whether the efficacy and safety of ticagrelor were similar early and late after randomization.. The PEGASUS-TIMI (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 randomized patients with prior MI (median 1.7 years prior) to ticagrelor 90 mg, ticagrelor 60 mg, or placebo on a background of aspirin. The rates of cardiovascular (CV) death, MI, and stroke as well as TIMI major bleeding were analyzed at yearly landmarks (years 1, 2, and 3).. A total of 21,162 patients were randomized and followed for 33 months (median), with 28% of patients ≥5 years from MI at trial conclusion. The risk of CV death, MI, or stroke in the placebo arm remained roughly constant over the trial at an ∼3% annualized rate. The benefit of ticagrelor 60 mg was consistent at each subsequent landmark (year 1 hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.67 to 0.99; year 2 HR: 0.90; 95% CI: 0.74 to 1.11; and year 3 HR: 0.79; 95% CI: 0.62 to 1.00). TIMI major bleeding was increased with ticagrelor 60 mg at each landmark, but with the greatest hazard in the first year (year 1 HR: 3.22; year 2 HR: 2.07; year 3 HR: 1.65).. Patients with a history of MI remain at persistent high risk for CVD, MI, and stroke as late as 5 years after MI. The efficacy of low-dose ticagrelor is consistent over time with a trend toward less excess bleeding. (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; Cause of Death; Dose-Response Relationship, Drug; Electrocardiography; Female; Follow-Up Studies; Global Health; Humans; Male; Middle Aged; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Survival Rate; Thrombolytic Therapy; Ticagrelor; Time Factors; Treatment Outcome

Topics: Aged; Clopidogrel; Cross-Over Studies; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Activation; Platelet Aggregation Inhibitors; Prospective Studies; Ticagrelor

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

The population pharmacokinetics of ticagrelor and its active metabolite AR-C124910XX were characterized following ticagrelor 60 mg or 90 mg twice daily oral long-term treatment in 4,426 patients with a history of myocardial infarction.. The ticagrelor and AR-C124910XX plasma concentration-time data were described by one-compartment models with first-order absorption or metabolite formation and elimination.. Systemic exposure to ticagrelor and AR-C124910XX were stable over time. Ticagrelor apparent clearance (CL/F) was 17 L/h for the 60-mg and 15.4 L/h for the 90-mg dose. The CL/F of AR-C124910XX was 11.1 L/h for the 60-mg and 9.95 L/h for the 90-mg dose. Both ticagrelor and AR-C124910XX CL/F were independently influenced by body weight, sex, age, smoking, and Japanese ethnicity. Female sex and age > 75 years were the only categorical covariates, having more than 20% effect on AR-C124910XX CL/F. Ticagrelor CL/F was 6% higher and 11% lower, whereas AR-C124910XX CL/F was 26% higher and 34% lower for patients weighing 110 and 50 kg, respectively, compared with an 83 kg patient.. The small differences in exposure to both ticagrelor and AR-C124910XX between demographic subgroups were in accordance with the consistent efficacy and safety outcomes observed across the population. The results were similar to those observed previously in patients with acute coronary syndromes.
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Topics: Activation, Metabolic; Adenosine; Administration, Oral; Aged; Aged, 80 and over; Drug Administration Schedule; Female; Gastrointestinal Absorption; Humans; Male; Middle Aged; Models, Biological; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor

Diabetes increases cardiovascular risk and reduces pharmacodynamic response to some oral antiplatelet drugs. This study aimed to determine whether ticagrelor 60 mg twice daily (bid) provided potent and consistent platelet inhibition in patients with vs without diabetes in the PEGASUS-TIMI 54 platelet function substudy. Out of 180 patients studied, 58 patients were randomised to and had received at least four weeks of ticagrelor 60 mg bid, with 20 (34 %) having diabetes, 58 patients received ticagrelor 90 mg bid, with 12 (21 %) having diabetes, and 64 patients received placebo, with 18 (28 %) having diabetes. Blood was sampled pre- and 2 hours post-maintenance dose. In patients treated with ticagrelor 60 mg bid, on-treatment platelet reactivity to ADP, as determined by light transmission aggregometry (LTA), VerifyNow and VASP, was similar in patients with vs without diabetes (LTA post-dose, ADP 20 µM: 29 ± 14 vs 34 ± 10 %, respectively; p = 0.19). A consistent inhibitory effect of ticagrelor 60 mg bid was observed pre- and post-dose regardless of diabetes status, even in insulin-treated patients. Patients with diabetes did not have an increased incidence of high platelet reactivity in either ticagrelor group. Platelet reactivity was similar in patients with diabetes treated with ticagrelor 60 mg vs 90 mg bid. Pharmacokinetics of ticagrelor were not affected by diabetes status. In conclusion, ticagrelor 60 mg bid is equally effective at reducing platelet reactivity in patients with and without diabetes, yielding a consistently high level of platelet inhibition regardless of diabetes status.

Topics: Adenosine; Aged; Biomarkers; Blood Platelets; Cell Adhesion Molecules; Diabetes Mellitus; Drug Administration Schedule; England; Female; Florida; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Male; Microfilament Proteins; Middle Aged; Myocardial Infarction; Phosphoproteins; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

The objective of this study was to assess the pharmacokinetic and pharmacodynamic behavior of ticagrelor administered either as crushed (in the semi-upright sitting position) or as integral (in the supine position) tablets in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI).. We randomized 20 patients to ticagrelor 180 mg either as 2 integral tablets administered in the supine position (standard administration) or as 2 tablets crushed and dispersed, administered in the semi-upright sitting position. Blood samples were drawn for pharmacokinetic and pharmacodynamic assessment at randomization (0 h) and at 0.5, 1, 2, and 4 h.. At 1 h, ticagrelor plasma exposure and area under the plasma concentration-time curve from time zero to 1 h (AUC1) (co-primary endpoints) were higher in the crushed versus integral tablets group (median 586 vs. 70.1 ng/mL and 234 vs. 24.4 ng·h/mL, respectively), with a ratio of adjusted geometric means (95% confidence interval [CI]) of 12.67 (2.34-68.51) [p = 0.005] and 19.28 (3.51-106.06) [p = 0.002], respectively. Time to maximum plasma concentration was shorter in the crushed versus integral tablets group (median 2 vs. 4 h), with a ratio of adjusted geometric means (95% CI) of 0.69 (0.49-0.97) [p = 0.035]. Parallel findings were observed with AR-C124910XX (active metabolite). Platelet reactivity (VerifyNow(®)) at 1 h was lower with crushed versus standard administration with least squares estimates mean difference (95% CI) of 92 (-158.4 to 26.6) P2Y12 reaction units (p = 0.009).. In patients with STEMI undergoing primary PCI, ticagrelor crushed tablets administered in the semi-upright sitting position seems to lead to a faster-compared with standard administration-absorption, with stronger antiplatelet activity within the first hour.. ClinicalTrials.gov identifier: NCT02046486.

Topics: Adenosine; Aged; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Posture; Purinergic P2Y Receptor Antagonists; Single-Blind Method; Tablets; Ticagrelor

Survivors after cardiac arrest (CA) due to AMI undergo PCI and then receive dual antiplatelet therapy. Mild therapeutic hypothermia (MTH) is recommended for unconscious patients after CA to improve neurological outcomes. MTH can attenuate the effectiveness of P2Y12 inhibitors by reducing gastrointestinal absorption and metabolic activation. The combined effect of these conditions on the efficacy of P2Y12 inhibitors is unknown. We compared the antiplatelet efficacies of new P2Y12 inhibitors in AMI patients after CA treated with MTH. Forty patients after CA for AMI treated with MTH and received one P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) were enrolled in a prospective observational single-center study. Platelet inhibition was measured by VASP (PRI) on days 1, 2, and 3 after drug administration. In-hospital clinical data and 1-year survival data were obtained. The proportion of patients with ineffective platelet inhibition (PRI > 50 %, high on-treatment platelet reactivity) for clopidogrel, prasugrel, and ticagrelor was 77 vs. 19 vs. 1 % on day 1; 77 vs. 17 vs. 0 % on day 2; and 85 vs. 6 vs. 0 % on day 3 (P < 0.001). The platelet inhibition was significantly worse in clopidogrel group than in prasugrel or ticagrelor group. Prasugrel and ticagrelor are very effective for platelet inhibition in patients treated with MTH after CA due to AMI, but clopidogrel is not. Using prasugrel or ticagrelor seems to be a more suitable option in this high-risk group of acute patients.

Topics: Adenosine; Aged; Clopidogrel; Female; Heart Arrest; Humans; Hypothermia, Induced; Male; Middle Aged; Myocardial Infarction; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Agonists; 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 currently available data indicate a drug-drug interaction between morphine and oral P2Y12 receptor inhibitors, when administered together. The aim of this trial was to assess the influence of infused morphine on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) in patients with acute myocardial infarction.. In a single-centre, randomized, double-blind trial, patients were assigned in a 1:1 ratio to receive intravenously either morphine (5 mg) or placebo, followed by a 180 mg loading dose of ticagrelor. Pharmacokinetics was determined with liquid chromatography tandem mass spectrometry and ticagrelor antiplatelet effects were measured with up to three different platelet function tests: vasodilator-stimulated phosphoprotein phosphorylation assay, multiple electrode aggregometry and VerifyNow. The pharmacokinetic and pharmacodynamic assessment was performed in 70 patients (35 in each study group). Morphine lowered the total exposure to ticagrelor and its active metabolite by 36% (AUC(0-12): 6307 vs. 9791 ng h/mL; P = 0.003), and 37% (AUC(0-12): 1503 vs. 2388 ng h/mL; P = 0.008), respectively, with a concomitant delay in maximal plasma concentration of ticagrelor (4 vs. 2 h; P = 0.004). Multiple regression analysis showed that lower AUC(0-12) values for ticagrelor were independently associated with the administration of morphine (P = 0.004) and the presence of ST-segment elevation myocardial infarction (P = 0.014). All three methods of platelet reactivity assessment showed a stronger antiplatelet effect in the placebo group and a greater prevalence of high platelet reactivity in patients receiving morphine.. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction. ClinicalTrials.gov Identifier: NCT02217878.

Topics: Adenosine; Administration, Oral; Analgesics, Opioid; Area Under Curve; Double-Blind Method; Drug Interactions; Female; Humans; Injections, Intravenous; Male; Middle Aged; Morphine; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Purinergic P2Y Receptor Antagonists; Ticagrelor

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

Among patients allocated to ticagrelor in the primary percutaneous coronary intervention (PCI) cohort of Platelet Inhibition and Patient Outcomes (PLATO) trial, 40.7% had received pre-randomization 600 mg of clopidogrel. This scenario is frequently employed in real-world practice. In a prospective, three-center, single-blind, parallel design study, 74 P2Y12 inhibitor-naive patients undergoing primary PCI were randomized (Hour 0) to ticagrelor 180 mg loading dose (LD) vs clopidogrel 600 mg LD followed after 2 h by ticagrelor 180 mg re-LD. Platelet reactivity (VerifyNow, in PRU) was assessed at Hour 0, 2, 4, 6, and 24. The primary comparison was non-inferiority of ticagrelor to clopidogrel followed by ticagrelor re-LD regarding platelet reactivity at 24 h using a prespecified margin of <35 PRU for the upper bound of the one-sided 97.5% confidence interval (CI). Ticagrelor was proven non-inferior to clopidogrel followed by ticagrelor re-LD with a difference between arms of 13.5 PRU (28.8 upper 97.5% CI), p = 0.001. At Hour 2, platelet reactivity was lower in ticagrelor only vs clopidogrel followed by ticagrelor re-LD groups with least square estimate mean difference (95% CI) -105.7 (-140.6 to -70.8), p < 0.001, without significant difference thereafter. In conclusion, in patients undergoing primary PCI, a strategy of ticagrelor LD only was proven non-inferior to clopidogrel LD followed by ticagrelor re-LD, in terms of antiplatelet efficacy at 24 h post-randomization and provided an earlier onset of platelet inhibition.

Topics: Adenosine; Biomarkers; Blood Platelets; Clopidogrel; Electrocardiography; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Risk Factors; Ticagrelor; Ticlopidine

The effects of ticagrelor in the subpopulation of patients with ST-elevation myocardial infarction (STEMI) were consistent with those observed in the overall Platelet Inhibition and Patient Outcomes (PLATO) study. However, this subgroup included patients initially or ultimately treated conservatively. The aim of this study is to compare treatment using ticagrelor with treatment using clopidogrel in patients with STEMI undergoing primary percutaneous coronary intervention (PCI).. This post-hoc subgroup analysis compared ticagrelor with clopidogrel in 4949 PLATO patients with STEMI that were treated with primary PCI within 12 h of admission. The primary endpoint was cardiovascular death, myocardial infarction or stroke. The safety endpoint consisted of any major bleeding. Secondary endpoints included stent thrombosis. The analysis was not adequately powered to establish significance of any treatment effects.. During a median of 286 days, the primary endpoint occurred in 7.9% of ticagrelor-treated patients versus 8.6% of clopidogrel-treated patients (HR 0.91, 95% CI 0.75 to 1.12, p=0.38). Major bleeding occurred in 6.7% in ticagrelor-treated patients versus 6.8% of clopidogrel-treated patients (HR 0.97, 95% CI 0.77 to 1.22, p=0.79). No interactions were observed for the treatment effect of ticagrelor versus clopidogrel on the primary efficacy (p=0.40) and primary safety endpoints (p=0.15) as compared with the full PLATO population. Treatment with ticagrelor versus clopidogrel reduced the occurrence of definite stent thrombosis (HR 0.58, 95% CI 0.37 to 0.89, p=0.013).. In the subset of patients with STEMI treated with primary PCI, ticagrelor compared with clopidogrel was safe, and efficacy outcomes were consistent with the overall PLATO trial.. NCT00391872; Results.

Topics: Adenosine; Aged; Clopidogrel; Combined Modality Therapy; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; Treatment Outcome

The Platelet Inhibition and Patient Outcomes (PLATO, Eur J Prev Cardiol 22(6):734-42, 2015) trial shows that, in patients who have an acute coronary syndrome, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death, but the reason is still uncertain. Both inflammation and vascular endothelian cell dysfunction play important roles in the pathophysiology of atherosclerotic plaques, but whether ticagrelor has superior anti-inflammatory effect and can improve vascular endothelial cell function to a great extent is unknown.. Patients with STEMI who are scheduled to undergo emergency percutaneous coronary intervention (PCI) will be randomly assigned to receive a loading dose of ticagrelor 180 mg as the treatment group or clopidogrel 600 mg as the control group. After PCI, the treatment group will be treated with ticagrelor 90 mg twice daily while the control group will be treated with clopidogrel 75 mg once daily. The vascular endothelial function will be tested by circulating endothelial cells, and levels of inflammation will be tested by CD40 ligand (CD40L), high sensitivity C-reactive protein (hsCRP) and P-selectin. The estimated enrollment sample size will be 350 patients, including 175 in the treatment group and 175 in the control group.. This study will compare the influence of ticagrelor and clopidogrel on inflammatory biomarkers and vascular endothelial function firstly for STEMI patients receiving emergency PCI and will provide evidence to identify whether ticagrelor inhibits inflammation and improves vascular endothelial cell function to a greater extent than clopidogrel or not.. This trial was registered with Clinicaltrials.gov (identifier: NCT02123004) on 20 April 2014.

Topics: Adenosine; Biomarkers; C-Reactive Protein; CD40 Ligand; Clinical Protocols; Clopidogrel; Endothelium, Vascular; Humans; Myocardial Infarction; P-Selectin; Percutaneous Coronary Intervention; Prospective Studies; Purinergic P2Y Receptor Antagonists; Sample Size; Ticagrelor; Ticlopidine

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 studied 2 doses of ticagrelor, 90 mg twice a day (bid) and 60 mg bid, for long-term prevention of ischemic events in patients with prior myocardial infarction. Both doses similarly reduced the rate of ischemic events versus placebo. The pharmacokinetics and pharmacodynamics of ticagrelor 60 mg bid have not been studied.. In this study, the authors sought to study the pharmacokinetics and pharmacodynamics for ticagrelor 60 mg compared with 90 mg bid.. A total of 180 patients who received >4 weeks of study medication had blood sampling in the morning pre-maintenance dose and again 2 h post-dose. All patients received aspirin. Plasma levels of ticagrelor and its active metabolite AR-C124910XX were determined. P2Y12 inhibition was assessed by the VerifyNow P2Y12 assay (Accumetrics, Inc., San Diego, California) (P2Y12 reaction units [PRU]), light transmittance aggregometry (adenosine diphosphate 5 and 20 μmol/l and arachidonic acid), and vasodilator-stimulated phosphoprotein phosphorylation assays. VerifyNow Aspirin assays and serum thromboxane B2 measurements were performed.. Mean pre- and post-dose plasma levels of ticagrelor were 35% and 38% lower, respectively, with 60 mg versus 90 mg. Both doses achieved high levels of platelet inhibition pre- and post-dose, with numerically slightly more variability with 60 mg: mean (SD) pre-dose PRU values were 59 ± 63 and 47 ± 43 for ticagrelor 60 and 90 mg, respectively (p = 0.34). High platelet reactivity, determined as PRU >208, was rare with the 60-mg pre-dose and was absent post-dose. Platelet reactivity pre- and post-dose, as measured by light transmittance aggregometry or vasodilator-stimulated phosphoprotein assays, was numerically but not significantly lower with 90 mg than with 60 mg. Aspirin response was not affected by either dose.. Ticagrelor 60 mg bid achieved high levels of peak and trough platelet inhibition in nearly all patients, similar to that with 90 mg bid, helping to explain the efficacy of the lower ticagrelor dose in PEGASUS-TIMI 54.

Topics: Adenosine; Blood Platelets; Dose-Response Relationship, Drug; Follow-Up Studies; Humans; Myocardial Infarction; Platelet Aggregation; Purinergic P2Y Receptor Antagonists; Ticagrelor; 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

Despite overwhelming data demonstrating the efficacy of antiplatelet therapy in heart disease and stroke, data in peripheral artery disease (PAD) are less compelling. Aspirin has modest evidence supporting a reduction in cardiovascular events in patients with PAD, whereas clopidogrel monotherapy may be more effective in PAD. Ticagrelor, a potent, reversibly binding P2Y12 receptor antagonist, is beneficial in patients with acute coronary syndrome and prior myocardial infarction. The EUCLID trial is designed to address the need for effective antiplatelet therapy in PAD to decrease the risk of cardiovascular events.. EUCLID is a randomized, double-blind, parallel-group, multinational clinical trial designed to evaluate the efficacy and safety of ticagrelor compared with clopidogrel for the prevention of major adverse cardiovascular events in subjects with symptomatic PAD. Subjects with established PAD will be randomized in a 1:1 fashion to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. The primary end point is a composite of cardiovascular death, myocardial infarction, or ischemic stroke. Other end points address limb events including acute leg ischemia, need for revascularization, disease progression by ankle-brachial index, and quality of life. The primary safety objective is Thrombolysis in Myocardial Infarction-defined major bleeding. Recruitment began in December 2012 and was completed in March 2014; 13,887 patients were randomized. The trial will continue until at least 1,364 adjudicated primary end points occur.. The EUCLID study is investigating whether treatment with ticagrelor versus clopidogrel, given as antiplatelet monotherapy, will reduce the incidence of cardiovascular and limb-specific events in patients with symptomatic PAD.

Topics: Adenosine; Aged; Ankle Brachial Index; Clopidogrel; Disease Progression; Female; Humans; Male; Middle Aged; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Ticlopidine; Treatment Outcome

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

The use of oral P2Y12 receptor inhibitors after acute myocardial infarction (MI) can reduce risks of subsequent major adverse cardiovascular events (composite of all-cause death, recurrent MI, and stroke), yet medication persistence is suboptimal. Although copayment cost has been implicated as a factor influencing medication persistence, it remains unclear whether reducing or eliminating these costs can improve medication persistence and/or downstream clinical outcomes.. ARTEMIS is a multicenter, cluster-randomized clinical trial designed to examine whether eliminating patient copayment for P2Y12 receptor inhibitor therapy affects medication persistence and clinical outcomes. We will enroll approximately 11,000 patients hospitalized for acute ST-elevation and non-ST-elevation MI at 300 hospitals. Choice and duration of treatment with a P2Y12 receptor inhibitor will be determined by the treating physician. Hospitals randomized to the copayment intervention will provide vouchers to cover patients' copayments for their P2Y12 receptor inhibitor for up to 1 year after discharge. The coprimary end points are 1-year P2Y12 receptor inhibitor persistence and major adverse cardiovascular events. Secondary end points include choice of P2Y12 receptor inhibitor, patient-reported outcomes, and postdischarge cost of care.. ARTEMIS will be the largest randomized assessment of a medication copayment reduction intervention on medication persistence, clinical outcomes, treatment selection, and cost of care after acute MI.

Topics: Adenosine; Clopidogrel; Cost Sharing; Drug Costs; Financial Support; Health Care Costs; Health Expenditures; Humans; Logistic Models; Medication Adherence; Mortality; Multivariate Analysis; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Recurrence; Secondary Prevention; Stroke; Ticagrelor; Ticlopidine; Treatment Outcome

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

Patients with myocardial infarction (MI) seldom reach recommended targets for secondary prevention. This study evaluated a smartphone application ("app") aimed at improving treatment adherence and cardiovascular lifestyle in MI patients.. Multicenter, randomized trial.. A total of 174 ticagrelor-treated MI patients were randomized to either an interactive patient support tool (active group) or a simplified tool (control group) in addition to usual post-MI care. Primary end point was a composite nonadherence score measuring patient-registered ticagrelor adherence, defined as a combination of adherence failure events (2 missed doses registered in 7-day cycles) and treatment gaps (4 consecutive missed doses). Secondary end points included change in cardiovascular risk factors, quality of life (European Quality of Life-5 Dimensions), and patient device satisfaction (System Usability Scale).. Patient mean age was 58 years, 81% were men, and 21% were current smokers. At 6 months, greater patient-registered drug adherence was achieved in the active vs the control group (nonadherence score: 16.6 vs 22.8 [P = .025]). Numerically, the active group was associated with higher degree of smoking cessation, increased physical activity, and change in quality of life; however, this did not reach statistical significance. Patient satisfaction was significantly higher in the active vs the control group (system usability score: 87.3 vs 78.1 [P = .001]).. In MI patients, use of an interactive patient support tool improved patient self-reported drug adherence and may be associated with a trend toward improved cardiovascular lifestyle changes and quality of life. Use of a disease-specific interactive patient support tool may be an appreciated, simple, and promising complement to standard secondary prevention.

Topics: Adenosine; Aged; Body Mass Index; Exercise; Female; Health Behavior; Humans; Kaplan-Meier Estimate; Male; Medication Adherence; Middle Aged; Mobile Applications; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Risk Reduction Behavior; Secondary Prevention; Smartphone; Smoking Cessation; Ticagrelor

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

No randomized head-to-head comparison of the efficacy and safety of ticagrelor and prasugrel has been published in the 7 years since the higher efficacy of these newer P2Y. This academic study was designed to compare the efficacy and safety of prasugrel and ticagrelor in acute myocardial infarction treated with primary or immediate percutaneous coronary intervention. A total of 1230 patients were randomly assigned across 14 sites to either prasugrel or ticagrelor, which was initiated before percutaneous coronary intervention. Nearly 4% were in cardiogenic shock, and 5.2% were on mechanical ventilation. The primary end point was defined as death, reinfarction, urgent target vessel revascularization, stroke, or serious bleeding requiring transfusion or prolonging hospitalization at 7 days (to reflect primarily the in-hospital phase). This analysis presents data from the first 30 days (key secondary end point). The total follow-up will be 1 year for all patients and will be completed in 2017.. The study was prematurely terminated for futility. The occurrence of the primary end point did not differ between groups receiving prasugrel and ticagrelor (4.0% and 4.1%, respectively; odds ratio, 0.98; 95% confidence interval, 0.55-1.73; P=0.939). No significant difference was found in any of the components of the primary end point. The occurrence of key secondary end point within 30 days, composed of cardiovascular death, nonfatal myocardial infarction, or stroke, did not show any significant difference between prasugrel and ticagrelor (2.7% and 2.5%, respectively; odds ratio, 1.06; 95% confidence interval, 0.53-2.15; P=0.864).. This head-to-head comparison of prasugrel and ticagrelor does not support the hypothesis that one is more effective or safer than the other in preventing ischemic and bleeding events in the acute phase of myocardial infarction treated with a primary percutaneous coronary intervention strategy. The observed rates of major outcomes were similar but with broad confidence intervals around the estimates. These interesting observations need to be confirmed in a larger trial.. URL: http://www.ClinicalTrials.gov. Unique identifier: NCT02808767.

Topics: Adenosine; Adult; Aged; Female; Humans; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor

For patients with coronary artery disease undergoing coronary bypass surgery, acetylsalicylic acid (ASA) currently represents the gold standard of antiplatelet treatment. However, adverse cardiovascular event rates in the first year after coronary artery bypass grafting (CABG) still exceed 10%. Graft failure, which is predominantly mediated by platelet aggregation, has been identified as a major contributing factor in this context. Therefore, intensified platelet inhibition is likely to be beneficial. Ticagrelor, an oral, reversibly binding and direct-acting P2Y12 receptor antagonist, provides a rapid, competent, and consistent platelet inhibition and has shown beneficial results compared with clopidogrel in the subset of patients undergoing bypass surgery in a large previous trial.. Ticagrelor is superior to ASA for the prevention of major cardiovascular events within 1 year after CABG.. The TiCAB trial (NCT01755520) is a multicenter, phase III, double-blind, double-dummy, randomized trial comparing ticagrelor with ASA for the prevention of major cardiovascular events within 12 months after CABG. Patients undergoing CABG will be randomized in a 1:1 fashion to either ticagrelor 90 mg twice daily or ASA 100 mg once daily. The study medication will be started within 24 hours after surgery and maintained for 12 months. The primary end point is the composite of cardiovascular death, myocardial infarction, stroke, and repeat revascularization at 12 months after CABG. The sample size is based on an expected event rate of 13% of the primary end point within the first 12 months after randomization in the control group, a 2-sided α level of .0492 (to preserve the overall significance level of .05 after planned interim analysis), a power of 0.80%, 2-sided testing, and an expected relative risk of 0.775 in the active group compared with the control group and a dropout rate of 2%. According to power calculations based on a superiority design for ticagrelor, it is estimated that 3,850 patients should be enrolled.. There is clinical equipoise on the issue of optimal platelet inhibition after CABG. The TiCAB trial will provide a pivotal comparison of the efficacy and safety of ticagrelor compared with ASA after CABG.

Topics: Adenosine; Aged; Aspirin; Cardiovascular Diseases; Coronary Artery Bypass; Coronary Artery Disease; Double-Blind Method; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Stroke; 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

Topics: Adenosine; Chemistry, Pharmaceutical; Humans; Internationality; Intubation, Gastrointestinal; Myocardial Infarction; Prospective Studies; Purinergic P2Y Receptor Antagonists; Tablets; Ticagrelor

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

Ticagrelor is an oral platelet P2Y12 receptor antagonist which is recommended for patients suffering from myocardial infarction, both with and without persistent ST segment elevation. Morphine is the first choice drug in pain alleviation in the same clinical subset. Recently a possible negative influence of morphine on the pharmacokinetics and antiplatelet effects of P2Y12 receptor blockers has been postulated.. The IMPRESSION study is a phase IV, single center, randomized, double-blind, placebo-controlled clinical trial that is designed to assess the influence of morphine on the pharmacokinetics and pharmacodynamics of ticagrelor in patients with myocardial infarction. The study is planned to include up to 100 patients with myocardial infarction who will be randomized into one of two arms in a 1:1 ratio. Subjects in the intervention arm prior to the loading dose of ticagrelor (180 mg) will receive morphine (5 mg) intravenously, whereas patients in the control arm will receive a placebo prior to the loading dose of ticagrelor (180 mg). The pharmacokinetics of ticagrelor and its active metabolite (AR-C124910XX) will be assessed by liquid chromatography mass spectrometry. Platelet function testing in each patient will be performed using up to four different methods (platelet vasodilator-stimulated phosphoprotein assay, multiple electrode aggregometry, VerifyNow, and light transmission aggregometry).. This study is expected to provide essential evidence-based data on the impact of morphine on the absorption of ticagrelor in patients with myocardial infarction as well as to shed some light on the suspected connection between morphine use and antiplatelet activity of ticagrelor in the same group of patients.. ClinicalTrials.gov identifier: NCT02217878 (14 August 2014).

Topics: Adenosine; Aged; Analgesics, Opioid; Biotransformation; Blood Platelets; Chromatography, Liquid; Clinical Protocols; Double-Blind Method; Drug Interactions; Drug Monitoring; Female; Humans; Male; Mass Spectrometry; Morphine; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Function Tests; Poland; Purinergic P2Y Receptor Antagonists; Research Design; Ticagrelor; Treatment Outcome

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

Guidelines recommend a ticagrelor loading dose (LD) before PCI or a prasugrel LD at the time of percutaneous coronary intervention (PCI) in intermediate and high-risk non-ST-elevation acute coronary syndrome (NSTE-ACS). However, achieving an optimal PR inhibition at the time of PCI is critical to prevent adverse events and depends on the timing of LD intake in relation to PCI. We aimed to compare the rate of myonecrosis related to PCI in patients with NSTE-ACS receiving ticagrelor pretreatment versus prasugrel at the time of intervention. We prospectively randomized 213 patients with NSTE-ACS to a 180 mg of ticagrelor LD given as soon as possible after admission and before PCI or to a 60 mg LD of prasugrel given at the time of PCI. The primary end point was the rate of periprocedural myonecrosis as defined by an increase of >5 times the ninety-ninth percentiles in troponin-negative patients or a 20% increase in troponin-positive patients. The 2 groups were similar regarding baseline characteristics including clinical setting (p = 0.2). Procedural characteristics were also identical including the number of treated vessels and stenting procedures. Patients in the prasugrel group more often required emergent PCI (p = 0.001). Patients in the ticagrelor group had less periprocedural myonecrosis compared with those in the prasugrel group (19.8% vs 38.3%; p = 0.03). The rate of major adverse cardiovascular events and Bleeding Academic Research Consortium ≥2 at 1-month follow-up was low and similar between the 2 groups. In conclusion, a ticagrelor LD as soon as possible before PCI is superior to prasugrel at the time of PCI to prevent periprocedural myonecrosis in NSTE-ACS.

Topics: Acute Coronary Syndrome; Adenosine; Adolescent; Adult; Aged; Dose-Response Relationship, Drug; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Piperazines; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Treatment Outcome; Young Adult

To evaluate the safety and efficacy of antiplatelet therapy of ticagrelor on patients suffering from acute ST segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.. In the study, 96 patients suffering from acute ST segment elevation myocardial infarction onset within 12 h undergoing primary percutaneous coronary intervention from May to October in 2013 were randomly divided into ticagrelor group (n=48) and clopidogrel group (n=48) by using the method of random number table. Ticagrelor and clopidogrel antiplatelet treatment were used before and after operation. Their baseline data, coronary artery disease characteristics, platelet count, adenosine diphosphate(ADP)-induced platelet inhibition rate by thrombelastograph after 5 days of treatment, the major adverse cardiovascular events of the follow up for 6 months and bleeding complications were observed and compared in the two groups.. The differences between the two groups of patients with their baseline data, the features of coronary artery lesions, platelet count before and after 5 days of treatment had no statistical significance (P>0.05). ADP induced platelet inhibition rate [(80.2±10.7)%] after 5 days of treatment in ticagrelor group was significantly higher than that in clopidogrel group [(75.3±12.1)%, P<0.05]. The two groups of patients were followed up for 6 months, 8 cases of major adverse cardiovascular events occurred in clopidogrel group, 2 cases of major adverse cardiovascular events occurred in ticagrelor group, and there was significant difference between the two groups (P<0.05). The two groups (7 cases of 48 patients in ticagrelor group vs. 3 cases of 48 patients in clopidogrel group) had no statistically significant difference in bleeding complications (P>0.05).. Antiplatelet therapy of ticagrelor on patients suffering from acute ST segment elevation myocardial infarction undergoing emergency PCI has good efficacy and safety.

Topics: Adenosine; Clopidogrel; Follow-Up Studies; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Ticlopidine

The risk of recurrent ischemia is high in the acute period after ischemic stroke and transient ischemic attack. Aspirin is recommended by guidelines for this indication, but more intensive antiplatelet therapy may be justified.. We aim to evaluate whether ticagrelor, a potent antiplatelet agent that blocks the P2Y12 receptor without requiring metabolic activation, reduces the risk of major vascular events compared with aspirin when randomization occurs within 24 h after symptom onset of a nonsevere ischemic stroke or high-risk transient ischemic attack.. Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) is a randomized, double-blind, event-driven trial and will include an estimated 13,600 participants randomized in 33 countries worldwide to collect 844 primary events.. The primary endpoint is the composite of stroke (ischemic or hemorrhagic), myocardial infarction, and death. Time to the first primary endpoint will be compared in the treatment groups during 90-day follow-up, with major hemorrhage serving as the primary safety endpoint. Participants will be followed for an additional 30 days after the randomized treatment period.. The SOCRATES trial fulfills an important clinical need by evaluating a potent antiplatelet agent as a superior alternative to current standard of care in patients presenting acutely with ischemic stroke or transient ischemic attack.

Topics: Adenosine; Aspirin; Double-Blind Method; Fibrinolytic Agents; Follow-Up Studies; Humans; Internationality; Ischemic Attack, Transient; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Research Design; Ticagrelor; Treatment Outcome

High on-treatment platelet reactivity (HTPR) is accompanied by an increased risk of adverse outcomes. Direct comparison of the antiplatelet effects between ticagrelor and high-dose clopidogrel has not yet been reported in acute myocardial infarction (AMI) or coronary artery in-stent restenosis (ISR) patients with HTPR. Consecutive patients with AMI or coronary artery ISR treated with standard-dose clopidogrel (75 mg/day) were screened with the VerifyNow assay, defining HTPR as P2Y12 reaction units (PRUs)>208. Of the 102 screened patients, 48 (47.06%) patients with HTPR were randomly assigned to either ticagrelor (180 mg/90 mg twice daily) or high-dose clopidogrel (150 mg/day) for 24 hours. Baseline characteristics and mean PRUs were similar in both groups. After 24 hours, ticagrelor was associated with a significantly lower platelet reactivity than high-dose clopidogrel (44.38±40.26  vs. 212.58±52.34 PRU, P<0.05). No patient receiving ticagrelor exhibited HTPR, whereas 15 (62.50%) patients after treatment with high-dose clopidogrel remained HTPR (P<0.05). During the follow-up (mean, 138.42±53.59 days), no patient exhibited a major bleeding event in either treatment group. In conclusion, in patients with AMI or coronary artery ISR exhibiting HTPR after standard clopidogrel treatment, ticagrelor is significantly more effective compared with high-dose clopidogrel in overcoming HTPR.

Topics: Adenosine; Aged; Clopidogrel; Coronary Angiography; Coronary Restenosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Activation; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; Treatment Outcome

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

The goal of this study was to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of escalating ticagrelor loading dose (LD) regimens in primary percutaneous coronary intervention (PPCI).. Patients with ST-segment elevation myocardial infarction undergoing PPCI frequently have suboptimal platelet inhibition in the early hours after ticagrelor LD. The use of high ticagrelor LD regimens has been hypothesized to optimize platelet inhibition in PPCI.. This was a prospective, randomized study of escalating ticagrelor LD regimens (180 mg, 270 mg, or 360 mg) in PPCI (N = 52). PK/PD analyses were performed before and 30 min, 1, 2, 4, 8, and 24 h post-LD. PK assessments included exposure to ticagrelor and its metabolite (AR-C124910XX). PD assessments included P2Y12 reaction units (PRU) measured by VerifyNow P2Y12 and platelet reactivity index (PRI) measured by vasodilator-stimulated phosphoprotein (VASP).. Platelet reactivity was elevated during the first 2 h post-LD. There were no differences in PRU between groups during the study time course (p = 0.179). There were no significant differences in PRU levels across groups at all time points, except at 1 h (p = 0.017) where platelet reactivity was lowest with a 270-mg LD. No differences were found between the 180-mg and 360-mg groups (primary endpoint; p > 0.999). High on-treatment platelet reactivity rates were not different across groups, except at 1 hour (p = 0.038). Parallel PD findings were observed with VASP-PRI. PK analysis showed a delay in ticagrelor absorption and generation of AR-C124910XX, irrespective of dose. Although morphine was associated with a delay in ticagrelor PK/PD, it was not an independent predictor of high on-treatment platelet reactivity.. ST-segment elevation myocardial infarction patients undergoing PPCI frequently exhibit impaired response to ticagrelor in the early hours after drug administration, which cannot be overcome by increasing LD regimens. These PD findings are largely attributed to an impaired PK profile, indicating a delay in drug absorption compared with that reported in stable clinical settings. (High Ticagrelor Loading Dose in STEMI; NCT01898442).

Topics: Adenosine; Aged; Biotransformation; Blood Platelets; Cell Adhesion Molecules; Dose-Response Relationship, Drug; Female; Humans; Intestinal Absorption; Male; Microfilament Proteins; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Phosphoproteins; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Ticagrelor; Treatment Outcome

This study aimed to compare preoperative treatment using clopidogrel and ticagrelor for patients with acute myocardial infarction (AMI) undergoing emergent percutaneous coronary intervention (PCI), and to investigate the efficacy and safety of these medications in the management of AMI.. Between February 2013 and December 2014, 74 patients with AMI admitted for emergent PCI therapy were included in the study and randomly divided into two groups: study group and control group. Patients in the study group received different pre-PCI treatment with a loading dose of 180 mg ticagrelor, and those in the control group received treatments with a loading dose of 600 mg clopidogrel. After PCI procedure, all patients were orally administered 75 mg clopidogrel once a day for maintenance therapy, and patients were monitored for one week at the hospital and further followed up for one month Platelet aggregation rates (PAR) of each patient was measured before medication, at 30 min, 2h, 24h and one week after medication, respectively. PAR, thrombolysis in myocardial infarction (TIMI) flow, clinical outcomes and adverse reactions were compared between groups.. No significant differences were observed in PAR before treatment between groups (p>0.05), whereas PARs were significantly different after treatment between groups (p<0.05), with the efficacy of medications peaking at 2h after the treatment. In addition, PARs were significantly different between different time points after treatment (p<0.05). Evaluation of TIMI flow grade showed that in study group, 6 patients (16.22%) were grade 2 and 31 (83.78%) were grade 3 for the study group; for the control group, 11 patients (27.73%) were grade 2 and 26 (72.27%) were grade 3. No significant differences were observed in TIMI flow grades between different groups (p>0.05). No recurrence of the disease was observed, but one case (2.70%) of mucosal bleeding in the nasal cavity and four cases (10.81%) of vomiting were found in the study group. However, in the control group, four patients (10.81%) presented with recurrent disease, six patients (16.22%) experienced mucosal bleeding in the nasal cavity and 11 patients (29.73%) vomited. Significant differences were observed in the incidence of adverse events between different groups (p<0.05).. Compared with 600 mg clopidogrel, a loading dose of 180 mg ticagrelor could effectively inhibit platelet reactivity at the early stage of AMI, resulting in more favorable clinical outcomes and lower occurrence of adverse events and, thereby, can be used in clinical practice.

Topics: Adenosine; Aged; Clopidogrel; Combined Modality Therapy; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Preoperative Care; Ticagrelor; Ticlopidine; Treatment Outcome

Topics: Adenosine; Adult; Aged; Female; Humans; Male; Middle Aged; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Thrombolytic Therapy; Ticagrelor

In acute coronary syndromes (ACS), a dual antiplatelet regimen with an adenosine diphosphate (ADP) receptor antagonist plus aspirin has become the cornerstone of treatment. The third-generation thienopyridine prasugrel and the cyclopentyl-triazolo-pyrimidine ticagrelor provide a greater, more rapid and consistent platelet inhibition compared to their predecessor clopidogrel. Based on their advantages over clopidogrel in two landmark studies, both drugs received a class I recommendation for their use in ACS patients with and without ST segment elevation. Due to differences in ACS populations and conditions investigated, the relative merits of ticagrelor versus prasugrel in the treatment of ACS patients with planned invasive strategy cannot be reliably estimated from independent trials. To date, no direct head-to-head comparison of ticagrelor and prasugrel in terms of clinical outcome exists. The aim of this multicenter, randomized, open-label trial is to assess whether ticagrelor is superior to prasugrel in ACS patients with planned invasive strategy.

Topics: Acute Coronary Syndrome; Adenosine; Clinical Protocols; Coronary Thrombosis; Drug Administration Schedule; Fibrinolytic Agents; Germany; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Research Design; Stents; Stroke; Thiophenes; Ticagrelor; Time Factors; Time-to-Treatment; Treatment Outcome

This study sought to report the treatment effect of ticagrelor on myocardial infarction (MI) and the strategy for and impact of event adjudication in the PLATO (Platelet Inhibition and Patient Outcomes) trial.. In PLATO, ticagrelor reduced cardiovascular death, MI, or stroke in patients with acute coronary syndromes (ACS).. A clinical events committee (CEC) prospectively defined and adjudicated all suspected MI events, on the basis of events reported by investigators and by triggers on biomarkers. Treatment comparisons used CEC-adjudicated data, and per protocol, excluded silent MI.. Overall, 1,299 (610 ticagrelor, 689 clopidogrel) MIs reported by the CEC occurred during the trial. Of these, 1,097 (504 ticagrelor, 593 clopidogrel) contributed to the primary composite endpoint. Site investigators reported 1,198 (580 ticagrelor, 618 clopidogrel) MIs. Ticagrelor significantly reduced overall MI rates (12-month CEC-adjudicated Kaplan-Meier rates: 5.8% ticagrelor, 6.9% clopidogrel; hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.75 to 0.95). Nonprocedural MI (HR: 0.86; 95% CI: 0.74 to 1.01) and MI related to percutaneous coronary intervention or stent thrombosis tended to be lower with ticagrelor. MIs related to coronary artery bypass graft surgery were few, but numerical excess was observed in patients assigned ticagrelor. Analyses of overall MIs using investigator-reported data showed similar results but did not reach statistical significance (HR: 0.88; 95% CI: 0.78 to 1.00).. In patients with ACS, ticagrelor significantly reduced the incidence of MI compared with clopidogrel, with consistent results across most MI subtypes. CEC procedures identified more MI endpoints compared with site investigators. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872).

Topics: Acute Coronary Syndrome; Adenosine; Aged; Blood Platelets; Double-Blind Method; Female; Follow-Up Studies; Global Health; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Purinergic P2Y Receptor Antagonists; Survival Rate; Ticagrelor; 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

Although prompt reperfusion treatment restores normal epicardial flow, microvascular dysfunction may persist in some patients with acute coronary syndrome (ACS). Impaired myocardial perfusion is caused by intraluminal platelets, fibrin thrombi and neutrophil plugging; antiplatelet agents play a significant role in terms of protecting against thrombus microembolization. A novel antiplatelet agent, ticagrelor, is a non-thienopyridine, direct P2Y12 blocker that has shown greater, more rapid and more consistent platelet inhibition than clopidogrel. However, the effects of ticagrelor on the prevention of microvascular dysfunction are uncertain. The present study is a comparison between clopidogrel and ticagrelor use for preventing microvascular dysfunction in patients with ST elevation or non-ST elevation myocardial infarction (STEMI or NSTEMI, respectively).. The TIME trial is a single-center, randomized, open-label, parallel-arm study designed to demonstrate the superiority of ticagrelor over clopidogrel. A total of 152 patients with a spectrum of STEMI or NSTEMI will undergo prospective random assignment to clopidogrel or ticagrelor (1:1 ratio). The primary endpoint is an index of microcirculatory resistance (IMR) measured after percutaneous coronary intervention (PCI); the secondary endpoint is wall motion score index assessed at 3 months by using echocardiography.. The TIME trial is the first study designed to compare the protective effect of clopidogrel and ticagrelor on coronary microvascular dysfunction in patients with STEMI and NSTEMI.. ClinicalTrials.gov: NCT02026219. Registration date: 24 December 2013.

Topics: Acute Coronary Syndrome; Adenosine; Clinical Protocols; Clopidogrel; Coronary Circulation; Coronary Vessels; Humans; Microcirculation; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Republic of Korea; Research Design; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome; Ultrasonography

In ST-elevation myocardial infarction (STEMI) patients, residual platelet reactivity soon after a loading dose (LD) of prasugrel or ticagrelor is higher than that reported for healthy volunteers or subjects with stable coronary artery disease; and the majority of primary percutaneous coronary intervention (PPCI) procedures with bivalirudin monotherapy are performed without proper platelet inhibition. However, ticagrelor LD is just the daily dose, whereas prasugrel LD is 6-fold the long-term daily dose. We hypothesized that an increased ticagrelor LD may result in a faster and more effective platelet inhibition as compared with the standard prasugrel LD.. Fifty patients with STEMI, pretreated with intravenous aspirin, undergoing PPCI were randomized to receive prasugrel 60-mg LD (n = 25) or ticagrelor 360-mg LD (n = 25). Residual platelet reactivity was assessed by VerifyNow at baseline and 1, 2, 4, and 12 hours after drug LD.. At the time of LD, 90% of enrolled patients had an aspirin reactivity unit value <550. P2Y12 reaction units 1 hour after the LD (study primary end point) were 236 (129-289) and 248 (115-304) in the prasugrel and ticagrelor group, respectively (P = .899). High residual platelet reactivity (P2Y12 reaction units ≥240) was found in 43% and 56% of patients (P = .386) at 1 hour and in 30% and 32% of patients (P = .907) at 2 hours, respectively. There was no significant difference in bleeding, arrhythmias, or dyspnea episodes in the 2 groups.. In patients with STEMI undergoing PPCI, double (360 mg) ticagrelor LD failed to achieve a faster and more intense platelet inhibition as compared with the standard prasugrel LD. Intravenously administered aspirin allowed to achieve a very early inhibition of acid arachidonic pathway.

Topics: Adenosine; Aged; Aspirin; Combined Modality Therapy; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Activation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Premedication; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Time Factors; 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

Topics: Adenosine; Blood Platelets; Follow-Up Studies; Humans; Myocardial Infarction; Piperazines; Platelet Activation; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Time Factors

The aim of this health economic analysis was to compare the cost-effectiveness of ticagrelor versus clopidogrel within the German health care system. A two-part decision model was adapted to compare treatment with ticagrelor or clopidogrel in a low-dose acetylsalicylic acid (ASA) cohort (≤150 mg) for all ACS patients and subtypes NSTEMI/IA and STEMI. A decision-tree approach was chosen for the first year after initial hospitalization based on trial observations from a subgroup of the PLATO study. Subsequent years were estimated by a Markov model. Following a macro-costing approach, costs were based on official tariffs and published literature. Extensive sensitivity analyses were performed to test the robustness of the model. One-year treatment with ticagrelor is associated with an estimated 0.1796 life-years gained (LYG) and gained 0.1570 quality-adjusted life-years (QALY), respectively, over the lifetime horizon. Overall average cost with ticagrelor is estimated to be EUR 11,815 vs. EUR 11,387 with generic clopidogrel over a lifetime horizon. The incremental cost-effectiveness ratio (ICER) was EUR 2,385 per LYG (EUR 2,728 per QALY). Comparing ticagrelor with Plavix(®) or the lowest priced generic clopidogrel, ICER ranges from dominant to EUR 3,118 per LYG (EUR 3,567 per QALY). These findings are robust under various additional sensitivity analyses. Hence, 12 months of ACS treatment using ticagrelor/ASA instead of clopidogrel/ASA may offer a cost-effective therapeutic option, even when the generic price for clopidogrel is employed.

Topics: Acute Coronary Syndrome; Adenosine; Adult; Atherosclerosis; Clopidogrel; Cost-Benefit Analysis; Decision Trees; Double-Blind Method; Drugs, Generic; Follow-Up Studies; Germany; Humans; Markov Chains; Models, Economic; Myocardial Infarction; Platelet Aggregation Inhibitors; Prospective Studies; Quality-Adjusted Life Years; Thrombosis; Ticagrelor; Ticlopidine; Time Factors

This study sought to compare the action of prasugrel and ticagrelor in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI).. It has been documented that prasugrel and ticagrelor are able to provide effective platelet inhibition 2 h after a loading dose (LD). However, the pharmacodynamic measurements after prasugrel and ticagrelor LD have been provided by assessing only healthy volunteers or subjects with stable coronary artery disease.. Fifty patients with STEMI undergoing PPCI with bivalirudin monotherapy were randomized to receive 60 mg prasugrel LD (n = 25) or 180 mg ticagrelor LD (n = 25). Residual platelet reactivity was assessed by VerifyNow at baseline and 2, 4, 8, and 12 h after LD.. Platelet reactivity units (PRU) 2 h after the LD (study primary endpoint) were 217 (12 to 279) and 275 (88 to 305) in the prasugrel and ticagrelor groups, respectively (p = NS), satisfying pre-specified noninferiority criteria. High residual platelet reactivity (HRPR) (PRU ≥240) was found in 44% and 60% of patients (p = 0.258) at 2 h. The mean time to achieve a PRU <240 was 3 ± 2 h and 5 ± 4 h in the prasugrel and ticagrelor groups, respectively. The independent predictors of HRPR at 2 h were morphine use (odds ratio: 5.29; 95% confidence interval: 1.44 to 19.49; p = 0.012) and baseline PRU value (odds ratio: 1.014; 95% confidence interval: 1.00 to 1.03; p = 0.046).. In patients with STEMI, prasugrel showed to be noninferior as compared with ticagrelor in terms of residual platelet reactivity 2 h after the LD. The 2 drugs provide an effective platelet inhibition 2 h after the LD in only a half of patients, and at least 4 h are required to achieve an effective platelet inhibition in the majority of patients. Morphine use is associated with a delayed activity of these agents. (Rapid Activity of Platelet Inhibitor Drugs Study, NCT01510171).

Topics: Adenosine; Aged; Aged, 80 and over; Comparative Effectiveness Research; Drug Monitoring; Electrocardiography; Female; Humans; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Activation; Platelet Function Tests; Prasugrel Hydrochloride; Preoperative Care; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Time Factors; Treatment Outcome

Topics: Adenosine; Aged; Blood Platelets; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

We evaluated whether electrocardiogram (ECG) characteristics were aligned with clinical outcomes and the effect of ticagrelor within the diverse spectrum of non-ST-elevation acute coronary syndrome patients enrolled in the PLATelet inhibition and patient Outcomes (PLATO) trial.. There were 8884 PLATO patients who had baseline ECGs assessed by a core laboratory; of these, 4935 had an ECG at hospital discharge that also was assessed. Associations with study treatment on vascular death or myocardial infarction within 1 year were examined.. At baseline, most patients had either no or ≤0.5 mm of ST-segment depression (57%); 26% had 1.0 mm, and 17% had more extensive depression (>1.0 mm). Across the baseline ST-segment depression strata, there was a consistent treatment benefit with ticagrelor versus clopidogrel on vascular death/myocardial infarction. The extent of residual ST-segment depression at discharge was similar in the treatment groups, and the treatment effect did not differ by the extent of discharge ST-segment depression. There was a progressive increase in vascular death/myocardial infarction with increasing extent of baseline ST-segment depression (1.0 mm [vs no/0.5 mm]: hazard ratio [HR] 1.22; 95% confidence interval [CI], 1.03-1.45; >1.0 mm: HR 1.49; 95% CI, 1.24-1.78; P <.001) and at discharge (HR 1.28; 95% CI, 1.02-1.61; HR 2.13; 95% CI, 1.54-2.95; P <.001).. The treatment effect of ticagrelor among non-ST-segment-elevation acute coronary syndrome patients was consistently expressed across all baseline ST-segment depression strata. There was no indication of an anti-ischemic benefit of ticagrelor as reflected on the discharge ECG. Our data affirm the independent prognostic relationship of both baseline and hospital discharge ST-segment depression on outcomes within 1 year in non-ST-segment-elevation acute coronary syndrome patients.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Cardiovascular Diseases; Clopidogrel; Cohort Studies; Electrocardiography; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Prognosis; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Topics: Adenosine; Aged; Emergency Medical Services; Humans; Myocardial Infarction; Piperazines; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor

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

The efficacy and safety of ticagrelor vs. clopidogrel in patients with acute coronary syndromes (ACS) are well documented in the PLATelet inhibition and patient Outcomes trial (PLATO). The aim of this study was to assess the long-term cost-effectiveness of treating ACS patients for 12 months with ticagrelor compared with generic clopidogrel.. Event rates, health-care costs, and health-related quality of life during 12 months of therapy with either ticagrelor or generic clopidogrel were estimated from PLATO. Beyond 12 months, quality-adjusted survival and costs were estimated conditional on whether a non-fatal myocardial infarction (MI), a non-fatal stroke, or no MI or stroke occurred during the 12 months of therapy. Lifetime costs, life expectancy, and quality-adjusted life years (QALYs) were estimated for both treatment strategies. Incremental cost-effectiveness ratios were presented from a health-care perspective in 2010 Euros (€) applying unit costs and life tables from a Swedish setting in the base-case analysis. Treatment with ticagrelor was associated with increased health-care costs of €362 and a QALY gain of 0.13 compared with generic clopidogrel, yielding a cost per QALY gained with ticagrelor of €2753. The cost per life year gained was €2372. The results were consistent in major subgroups. Sensitivity analyses showed a cost per QALY gained with ticagrelor of ∼€7300 under certain scenarios.. Based on clinical and health-economic evidence from the PLATO study, treating ACS patients with ticagrelor for 12 months is associated with a cost per QALY below generally accepted thresholds for cost-effectiveness. ClinicalTrials.gov Identifier: NCT00391872.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Cost-Benefit Analysis; Female; Humans; Life Expectancy; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Quality-Adjusted Life Years; Stroke; Ticagrelor; Ticlopidine; Treatment Outcome

Topics: Adenosine; Adenosine Diphosphate; Blood Platelets; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Predictive Value of Tests; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Thiophenes; Ticagrelor; Time Factors; Treatment Outcome

We sought to evaluate the effect of potent platelet inhibition after acute coronary syndrome on total (ie, first and recurrent) occurrences of any of the primary outcome events (e.g., cardiovascular death, myocardial infarction, and stroke) as well as on other ischemic events, such as urgent revascularization, (severe) recurrent ischemia, transient ischemic attacks, and arterial thrombotic events.. In the PLATelet inhibition and patient Outcomes (PLATO) study, 18 624 patients presenting with acute coronary syndromes randomly received ticagrelor (n=9333) or clopidogrel (n=9291). Cox proportional hazard models were used to calculate time to first event and hazard ratios. Total events were compared using a Poisson regression model, and time to second event or death was calculated with the Wei Lin Weissfeld method. Patients randomized to ticagrelor had 1057 total primary end point events versus 1225 for patients on clopidogrel (rate ratio, 0.86; 95% confidence interval, 0.79-0.93; P=0.003). The number of additional events was numerically lower for ticagrelor (189 versus 205; P=0.40), resulting in a hazard for time to second event/death of 0.80 (95% confidence interval, 0.70-0.90; P<0.001) and a number needed to treat of 54. For cardiovascular death/myocardial infarction/stroke/(severe) recurrent ischemia/transient ischemic attack/arterial thrombotic events, total events were fewer with ticagrelor (2030 versus 2290; rate ratio, 0.88; 95% confidence interval, 0.82-0.95; P<0.001), with fewer recurrent events with ticagrelor (740 versus 834; P=0.01) and a highly significant concurrent reduction in hazard for time to second event or death of 0.83 (95% confidence interval, 0.75-0.91; P<0.001). Recurrent PLATO major or Thrombolysis in Myocardial Infarction (TIMI) major non-coronary artery bypass graft bleeding events were infrequent and not different between the two therapies (P=0.96 and 0.38, respectively).. In PLATO, treatment with ticagrelor compared with clopidogrel resulted in a reduction in total events, including first and subsequent recurrent cardiovascular events, when compared with clopidogrel. These types of analyses demonstrate an even greater absolute benefit of ticagrelor over clopidogrel than previously reported.. URL: http://www.clinicaltrials.gov/. Unique identifier: NCT00391872.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aged, 80 and over; Clopidogrel; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Severity of Illness Index; Stroke; Thrombosis; Ticagrelor; Ticlopidine; Treatment Outcome

The present trial aims at examining whether antiplatelet regimen modification, guided by assessment of the on-treatment platelet reactivity, might result with clinical benefit in moderate to high-risk patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).. High platelet reactivity has been associated with an increased rate of ischemic events after PCI. Recent large trials did not show a clinical benefit of platelet reactivity-guided therapy modification in acute coronary syndrome patients treated by PCI.. PLATFORM is an investigator-initiated, prospective, randomized, parallel-group, controlled clinical trial. Approximately 632 STEMI patients with intermediate to high-risk (RISK-PCI score >3) clinical features undergoing PPCI will be randomly allocated to treatment modification or standard therapy. Low responders to aspirin will receive 200 mg aspirin for 30 days. Low responders to clopidogrel will receive 180 mg ticagrelor for 1 year. The primary end-point is the time to the first composite major adverse cardiovascular events (MACE) including death, nonfatal infarction, stroke, or immediate target vessel revascularization. Key safety end-point is the rate of TIMI major bleeding unrelated to coronary artery bypass graft surgery. Our secondary end-points are individual components of MACE, definite stent thrombosis, total bleeding, and the need for blood transfusions. Patients will be followed-up at 30 days and at 1 year after PPCI.. PLATFORM will determine whether the platelet reactivity-guided use of ticagrelor in combination with 200 mg aspirin, compared with standard antiplatelet regimen, improves clinical outcome in moderate to high-risk STEMI patients undergoing PPCI.. U.S. National Institutes of Health (NIH) at www.clinicaltrials.gov. ClinicalTrials.gov Identifier: NCT01739556, and Current Controlled Trials at www.controlledtrials.com. International Standard Randomized Controlled Trial Number ISRCTN83081599.

Topics: Adenosine; Aspirin; Clopidogrel; Drug Therapy, Combination; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Prospective Studies; Ticagrelor; Ticlopidine; Treatment Outcome

We evaluated the predictive ability of cystatin C and creatinine-based estimations of glomerular filtration rate (eGFR), including the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation, in acute coronary syndrome (ACS) patients with (STE-ACS) or without (NSTE-ACS) ST elevation in a large contemporary ACS population.. Concentrations of cystatin C and creatinine, as well as eGFR at randomization, were measured in 16 401 patients in the Platelet Inhibition and Patient Outcomes (PLATO) study and evaluated as predictors of the composite end point of cardiovascular death or myocardial infarction within 1 year. Two Cox proportional hazards models were used, the first adjusting for clinical characteristics and the second for clinical characteristics plus the biomarkers N-terminal pro-B-type natriuretic peptide, troponin I, and C-reactive protein.. The median cystatin C value was 0.83 mg/L. Increasing quartiles of cystatin C were strongly associated with poor outcome (6.9%, 7.1%, 9.5%, and 16.2%). The fully adjusted hazard ratios per SD of cystatin C in the NSTE-ACS and STE-ACS populations were 1.12 (95% CI 1.04-1.20) (n=8053) and 1.06 (95% CI 0.97-1.17) (n=5278), respectively. There was no significant relationship of cystatin C with type of ACS (STE or NSTE). c Statistics ranged from 0.6923 (cystatin C) to 0.6941 (CKD-EPI).. Cystatin C concentration contributes independently in predicting the risk of cardiovascular death or myocardial infarction in NSTE-ACS, with no interaction by type of ACS. CKD-EPI exhibited the largest predictive value of all renal markers. Nevertheless, the additive predictive value of cystatin C or creatinine-based eGFR measures in the unselected ACS patient is small.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Biomarkers; C-Reactive Protein; Clopidogrel; Creatinine; Cystatin C; Double-Blind Method; Endpoint Determination; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Platelet Aggregation Inhibitors; Predictive Value of Tests; Proportional Hazards Models; Protein Precursors; Ticagrelor; Ticlopidine; Troponin I

Ticagrelor, when compared with clopidogrel, reduced the 12-month risk of vascular death/myocardial infarction and stroke in patients with ST-elevation acute coronary syndromes intended to undergo primary percutaneous coronary intervention in the PLATelet inhibition and patient Outcomes (PLATO) trial. This prespecified ECG substudy explored whether ticagrelor's association with vascular death and myocardial infarction within 1 year would be amplified by (1) the extent of baseline ST shift and (2) subsequently associated with fewer residual ST changes at hospital discharge.. ECGs were evaluated centrally in a core laboratory in 3122 ticagrelor- and 3084 clopidogrel-assigned patients having at least 1 mm ST-elevation in 2 contiguous leads as identified by site investigators on the qualifying ECG. Patients with greater ST-segment shift at baseline had higher rates of vascular death/myocardial infarction within 1 year. Among those who also had an ECG at hospital discharge (n=4798), patients with ≥50% ΣST-deviation (ΣST-dev) resolution had higher event-free survival than those with incomplete resolution (6.4% versus 8.8%, adjusted hazard ratio 0.69 (0.54-0.88), P=0.003). The extent of ΣST-dev resolution was similar irrespective of treatment assignment. The benefit of ticagrelor versus clopidogrel on clinical events was consistent irrespective of the extent of baseline ΣST-dev (P(interaction)=0.728). When stratified according to conventional times from symptom onset, ie, ≤3 hours, 3 to 6 hours, >6 hours, the extent of baseline ΣST-dev declined progressively over time. As time from symptom onset increased beyond 3 hours, the benefit of ticagrelor appeared to be more pronounced; however, the interaction between time and treatment was not significant (P=0.175).. Ticagrelor did not modify ΣST-dev resolution at discharge nor was its benefit affected by the extent of baseline ΣST-dev. These hypothesis-generating observations suggest that the main effects of ticagrelor may not relate to the rapidity or the completeness of acute reperfusion, but rather the prevention of recurrent vascular events by more powerful platelet inhibition or other mechanisms.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

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

The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) remains unclear.. We examined the relationship between PPI use and 1-year cardiovascular events (cardiovascular death, myocardial infarction, or stroke) in patients with acute coronary syndrome randomized to clopidogrel or ticagrelor in a prespecified, nonrandomized subgroup analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial. The primary end point rates were higher for individuals on a PPI (n=6539) compared with those not on a PPI (n=12 060) at randomization in both the clopidogrel (13.0% versus 10.9%; adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.04-1.38) and ticagrelor (11.0% versus 9.2%; HR, 1.24; 95% CI, 1.07-1.45) groups. Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI (PPI versus non-PPI gastrointestinal treatment: clopidogrel, HR, 0.98; 95% CI, 0.79-1.23; ticagrelor, HR, 0.89; 95% CI, 0.73-1.10). In contrast, patients on no gastric therapy had a significantly lower primary end point rate (PPI versus no gastrointestinal treatment: clopidogrel, HR, 1.29; 95% CI, 1.12-1.49; ticagrelor, HR, 1.30; 95% CI, 1.14-1.49).. The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel. However, a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment. Therefore, in the PLATO trial, the association between PPI use and adverse events may be due to confounding, with PPI use more of a marker for, than a cause of, higher rates of cardiovascular events.. http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Topics: Adenosine; Aged; Clopidogrel; Double-Blind Method; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Stroke; Ticagrelor; Ticlopidine; Treatment Outcome

Baseline Q waves may provide additional value compared with time from the onset of symptoms in predicting outcomes for patients with ST-segment elevation. We evaluated whether baseline Q waves superseded time from symptom onset as a prognostic marker of one-year mortality in patients with ST-segment elevation acute coronary syndrome. Our study was derived from data from patients undergoing primary percutaneous coronary intervention within 24 hours in the PLATelet inhibition and patient Outcomes trial. Q waves on the baseline electrocardiogram were evaluated by a blinded core laboratory. We assessed the associations between baseline Q waves and time from symptom onset to percutaneous coronary intervention with peak biomarkers, ST-segment resolution on the discharge electrocardiogram, and one-year all-cause and vascular mortality.. Of 4341 patients with ST-segment elevation, 46% had baseline Q waves. Compared to those without Q waves, those with baseline Q waves were older, more frequently male, had higher heart rates, more advanced Killip class and had a longer time between the onset of symptoms and percutaneous coronary intervention. They also had higher one-year all-cause mortality than patients without baseline Q waves (baseline Q waves: 4.9%; no baseline Q waves: 2.8%; hazard ratio [HR] 1.78, 95% confidence interval [CI] 1.29-2.45, p < 0.001). Complete ST-segment resolution was greatest and all-cause mortality lowest among those with symptom onset three hours or less before percutaneous coronary intervention and no baseline Q waves. After multivariable adjustment, baseline Q waves, but not time from symptom onset, were associated with a significant increase in all-cause mortality (adjusted HR 1.42, 95% CI 1.10-2.01, p = 0.046) and vascular mortality (adjusted HR 1.58, 95% CI 1.09-2.28, p = 0.02).. The presence of baseline Q waves provides useful additional prognostic insight into the clinical outcome of patients with ST-segment elevation. Clinical Trials.gov registration no. NCT00391872.

Topics: Acute Coronary Syndrome; Adenosine; Angioplasty, Balloon, Coronary; Biomarkers; Clopidogrel; Creatine Kinase, MB Form; Double-Blind Method; Electrocardiography; Female; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Prognosis; Prospective Studies; Purinergic P2Y Receptor Antagonists; Survival Analysis; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome; Troponin I; Troponin T

Ticagrelor is a new, direct acting, reversibly binding P2Y12 receptor antagonist with more potent inhibition of platelets than clopidogrel and which does not require metabolic activation. It was compared with clopidogrel, on a background of the standard of care in a randomized trial in the Platelet Inhibition and Patient Outcomes (PLATO) study, on patients with acute coronary syndrome (ACS). The purpose was to evaluate the efficacy and safety results from the global, prospective trial in a broad population [ST-elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI) patients] with ACS.. The main findings were a significant reduction of the primary outcome (death from vascular causes/myocardial infarction/stroke) with ticagrelor versus clopidogrel [9.8 versus 11.7% (hazard ratio 0.84; 95% confidence interval: 0.77-0.92); P < 0.001] without a significant increase in PLATO-defined major bleeding (11.6 versus 11.2%, respectively; P = 0.43), but a higher occurrence of noncoronary artery bypass grafting (CABG) related major bleeding (4.5 versus 3.8%; P = 0.026). In addition, there was a significant reduction in vascular mortality (4.0 versus 5.1%; P = 0.001). The findings were consistent in all subgroups, such as for STEMI, NSTEMI, planned invasive or noninvasive strategy, diabetes, renal function, and CABG.. Among patients with an ACS 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 nonprocedure-related bleeding.

Topics: Acute Coronary Syndrome; Adenosine; Blood Platelets; Clopidogrel; Confidence Intervals; Humans; Myocardial Infarction; Outcome Assessment, Health Care; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Statistics as Topic; Ticagrelor; Ticlopidine; United States

Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages.. We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2%) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5% versus 6.0%), death (10.5% versus 4.9%), stroke (3.4% versus 1.2%), and intracranial bleeding (0.8% versus 0.2%) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66-1.13; interaction P=0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively).. Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality.. URL: http://www.clinicatrials.gov. Unique identifier: NCT00391872.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Brain Ischemia; Clopidogrel; Female; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Male; Middle Aged; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Risk Factors; Stroke; Ticagrelor; Ticlopidine

Ticagrelor and prasugrel provide stronger platelet inhibition compared with clopidogrel. Direct pharmacodynamic comparison between them has not yet been reported in ST-segment-elevation myocardial infarction patients.. In a prospective, single-center, single-blind study, 55 out of 117 (47%) screened consecutive ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention were randomized to either ticagrelor 180 mg loading followed by 90 mg bid, or prasugrel 60 mg loading followed by 10 mg od for 5 days. Platelet reactivity (PR) was assessed with the VerifyNow P2Y12 function assay and the Multiplate Analyzer at 0, 1, 2, 6, 24 hours, and 5 days postrandomization. The primary end point, PR with VerifyNow at hour 1, did not differ significantly between patients randomized to ticagrelor versus prasugrel (257.3 P2Y12 reaction unit [PRU], 95% CI 230.8-283.8 versus 231.3 PRU, 95% CI 205.3-257.4; P=0.2). PR did not differ at 2, 6, and 24 hours, although at day 5 it was lower with ticagrelor than prasugrel (25.6 PRU, 95% CI 12.3-38.9 versus 50.3 PRU, 95% CI 36.4-64.1; P=0.01). At hour 2, high on-treatment PR rates (cutoff 208 PRU) were 46.2% and 34.6% for ticagrelor and prasugrel, respectively, decreased significantly thereafter, whereas did not differ significantly between the 2 agents at all the time points of the study.. In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, both ticagrelor and prasugrel exhibit an initial delay in the onset of their antiplatelet action. Ticagrelor did not appear superior to prasugrel in reducing PR during the first 24 hours of ST-segment-elevation myocardial infarction.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01463163.

Topics: Adenosine; Aged; Blood Platelets; Drug Administration Schedule; Female; Greece; Humans; Least-Squares Analysis; Linear Models; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Single-Blind Method; Thiophenes; Ticagrelor; Time Factors; Treatment Outcome

In the Platelet Inhibition and Patient Outcomes (PLATO) trial, a prespecified subgroup analysis showed a significant interaction between treatment and region (P=0.045), with less effect of ticagrelor in North America than in the rest of the world.. Reasons for the interaction were explored independently by 2 statistical groups. Systematic errors in trial conduct were investigated. Statistical approaches evaluated the likelihood of play of chance. Cox regression analyses were performed to quantify how much of the regional interaction could be explained by patient characteristics and concomitant treatments, including aspirin maintenance therapy. Landmark Cox regressions at 8 time points evaluated the association of selected factors, including aspirin dose, with outcomes by treatment. Systematic errors in trial conduct were ruled out. Given the large number of subgroup analyses performed and that a result numerically favoring clopidogrel in at least 1 of the 4 prespecified regions could occur with 32% probability, chance alone cannot be ruled out. More patients in the United States (53.6%) than in the rest of the world (1.7%) took a median aspirin dose ≥300 mg/d. Of 37 baseline and postrandomization factors explored, only aspirin dose explained a substantial fraction of the regional interaction. In adjusted analyses, both Cox regression with median maintenance dose and landmark techniques showed that, in patients taking low-dose maintenance aspirin, ticagrelor was associated with better outcomes compared with clopidogrel, with statistical superiority in the rest of the world and similar outcomes in the US cohort.. The regional interaction could arise from chance alone. Results of 2 independently performed analyses identified an underlying statistical interaction with aspirin maintenance dose as a possible explanation for the regional difference. The lowest risk of cardiovascular death, myocardial infarction, or stroke with ticagrelor compared with clopidogrel is associated with a low maintenance dose of concomitant aspirin.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Topics: Adenosine; Aged; Aspirin; Clopidogrel; Combined Modality Therapy; Female; Global Health; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Proportional Hazards Models; Purinergic P2Y Receptor Antagonists; Risk Factors; Stroke; Ticagrelor; Ticlopidine; United States

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

Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the mainstay regimen for acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI). We aimed to investigate DAPT compliance and switching patterns in ACS patients prescribed ticagrelor and aspirin. Secondly, we evaluated the impact of a pilot strategy of close surveillance telephone calls.. The study enrolled 150 consecutive ACS patients who underwent PCI and were prescribed DAPT (aspirin and ticagrelor). This cohort, the "close surveillance arm," then received telephone calls from a healthcare professional to inquire about DAPT for up to one year. These findings, and clinical outcomes, were then compared to a "historical arm" of ACS patients (n = 505) who received PCI and were prescribed DAPT before initiation of the program. Finally, healthcare providers were surveyed about their experience with prescribing DAPT.. The rate of ticagrelor cessation trended lower in the close surveillance arm (22.00 % versus 31.70 %, p = 0.0783). The most common reasons for ticagrelor cessation were adverse medication reaction (dyspnea), bleeding, and financial burden. Nevertheless, the adverse events were few and similar between the two groups during follow-up. Over 96 % of healthcare providers surveyed stated that they worry about their patients' DAPT compliance post-PCI.. Noncompliance and switching medications are still common for patients who undergo PCI for ACS. A close surveillance program identified patients at risk for medication cessation or switching and could potentially mitigate this phenomenon and improve quality of care.

Topics: Acute Coronary Syndrome; Aspirin; Drug Therapy, Combination; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; 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

To compare the long-term clinical outcomes of dual antiplatelet therapy (DAPT) with clopidogrel and DAPT with ticagrelor or prasugrel in patients with acute myocardial infarction (AMI) who underwent coronary intervention.. Between November 2011 and December 2015, a total of 13,104 patients with AMI were enrolled in the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) registry. Among them, 4,696 patients who received DAPT for more than 24 months were categorized into two groups: the clopidogrel group (n = 4,053) and ticagrelor or prasugrel group (n = 643). Propensity score matching (PSM) was used to reduce the bias due to confounding variables. Following PSM, the impacts of P2Y12 inhibitors on the clinical outcomes in both groups were compared during a 36-month clinical follow-up period.. There were no significant differences in clinical outcomes in terms of cardiac death (7.1% vs. 9.7%, p = 0.101), stroke (1.4% vs. 1.0%, p = 0.436), major bleeding (0.5% vs. 0.8%, p = 0.478), major adverse cardiac events (MACE) (21.6% vs. 20.5%, p = 0.626), and net adverse cardiac event (NACE) (22.1% vs. 21.3%, p = 0.731) between the groups. The ticagrelor or prasugrel group had a lower incidence of recurrent percutaneous coronary intervention (PCI) (12.2% vs. 7.6%, p = 0.006) than the clopidogrel group. However, no differences were observed in the cumulative incidences of 3-year NACE between the ticagrelor or prasugrel and clopidogrel groups.. Cumulative incidences of long-term NACE did not differ between the two groups. Therefore, the type and duration of DAPT should be customized for each patient with AMI.

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

Background Effectiveness estimates from observational studies on ticagrelor use in routine clinical care are conflicting, with some contrary to the results of the pivotal randomized controlled trial of ticagrelor in acute coronary syndrome. The aim of this study was to estimate the effect of implementing and using ticagrelor in routine clinical care in patients with myocardial infarction using a natural experimental approach. Methods and Results This is a retrospective cohort study including patients hospitalized for myocardial infarction in Sweden between 2009 and 2015. The study exploited differences in the timing and speed of ticagrelor implementation between treatment centers as a source of random treatment assignment. The effect of implementing and using ticagrelor was estimated based on the admitting center's likelihood of treating patients with ticagrelor, measured as the proportion of patients treated in the 90 days before patient admission. The main outcome was 12-month mortality. The study included 109 955 patients, of whom 30 773 were treated with ticagrelor. Being admitted to a treatment center with higher past ticagrelor use was associated with a reduction in 12-month mortality (2.5 percentage points for 100% versus 0% past use [95% CI, 0.2-4.8]). The results are in line with the findings from the ticagrelor pivotal trial. Conclusions Using a natural experiment, this study finds that the implementation and use of ticagrelor in routine clinical care has reduced 12-month mortality in patients admitted to the hospital with myocardial infarction in Sweden and supports the external validity of randomized evidence on ticagrelor effectiveness.

Topics: Acute Coronary Syndrome; Humans; Myocardial Infarction; Retrospective Studies; Sweden; 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

The pleiotropic action of ticagrelor, with effects in addition to platelet inhibition, has been shown to improve endothelial function in patients with coronary artery disease. These positive effects are possibly adenosine mediated. This study investigated the association of ticagrelor therapy and coronary artery flow reserve in survivors of myocardial infarction (MI).. This was an exploratory, cross-sectional, open substudy of PROFLOW. High-risk individuals with a history of MI were identified. Coronary flow reserve (CFR) was measured non-invasively in the left anterior descending artery using transthoracic Doppler echocardiography. Coronary flow velocity was measured at rest and at maximal flow after induction of hyperaemia by intravenous infusion of adenosine at 140 μg/kg/min. Patients receiving ticagrelor (n=75) were compared with those not receiving ticagrelor (n=506), using simple and multiple linear regression models. Most patients in both groups were treated with aspirin (97% in the ticagrelor and 94% in the non-ticagrelor group). Adjustment for traditional risk factors was conducted.. The mean age at study inclusion was 68.5±6.8 years, and most patients were male (81.8%). The simple linear regression analysis showed ticagrelor treatment to be significantly associated with increased CFR: ticagrelor 2.95±0.76 (mean±SD), non-ticagrelor 2.70±0.77, (coefficient 0.25; 95% CI 0.063-0.438; p=0.009). This association was significant in two of the three multiple linear regression models with increasing numbers of variables: Model 1 (0.28; 0.06-0.50; p=0.014), Model 2 (0.26; 0.03-0.48; p=0.025), and borderline significant in Model 3 (0.21; -0.01 to 0.43; p=0.058).. Ticagrelor treatment was associated with increased CFR in this high-risk population. Increased CFR may be a clinically important therapeutic effect of ticagrelor in addition to platelet inhibition.

Topics: Adenosine; Coronary Circulation; Cross-Sectional Studies; Female; Humans; Male; Myocardial Infarction; Survivors; Ticagrelor

Ticagrelor is widely used in patients with stable and acute coronary artery disease. Understanding the factors that influence its pharmacokinetics (PK) and pharmacodynamics (PD) could improve therapeutic outcomes. We therefore performed a pooled population PK/PD analysis using individual patient data from two studies. We focused on the impact of morphine administration and ST-segment elevation myocardial infarction (STEMI) on the risk of high platelet reactivity (HPR) and dyspnea.. A parent-metabolite population PK/PD model was developed based on data from 63 STEMI, 50 non-STEMI, and 25 chronic coronary syndrome (CCS) patients. Simulations were then run to evaluate the risk of non-response and adverse events associated with the identified variability factors.. The final PK model consisted of first-order absorption with transit compartments, distribution with two compartments for ticagrelor and one compartment for AR-C124910XX (active metabolite of ticagrelor), and linear elimination for both drugs. The final PK/PD model was an indirect turnover model with production inhibition. Morphine dose and STEMI, independently, had a significant negative effect on the absorption rate (reduction of log([Formula: see text]) by 0.21×morphine dose (mg) and by 2.37 in STEMI patients, both p < 0.001), and the presence of STEMI significantly impacted both efficacy and potency (both p < 0.001). The simulations run with the validated model showed a high rate of non-response in patients with those covariates (RR 1.19 for morphine, 4.11 for STEMI and 5.73 for morphine and STEMI, all three p < 0.001). By increasing ticagrelor dosage, the negative morphine effect was reversible in patients without STEMI and just limited in patients with STEMI.. The developed population PK/PD model confirmed the negative impact of morphine administration and presence of STEMI on ticagrelor PK and antiplatelet effect. Increasing ticagrelor doses seems effective in morphine users without STEMI, whereas the STEMI effect is not entirely reversible.

Topics: Humans; Morphine; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

A simple HPLC method was developed for the determination of antiplatelet drug ticagrelor (TCG) in blood. Sample preparation and extraction conditions were investigated and optimized. The preparation of blood plasma was investigated by protein precipitation using perchloric acid, methanol, acetonitrile (ACN), and trifluoroacetic acid. Protein precipitation using ACN was found to be the most suitable. Chromatographic separation of TCG was performed on a C18 column with a mobile phase consisting of ACN and 15 mM ammonium acetate buffered at pH 8.0. The method was applied to determine TCG in blood plasma of patients who had a heart attack. Blood samples were collected 1.5 h after the administration of the initial loading dose of the antiplatelet drug. The average concentration of TCG was found to be 0.97 ± 0.53 μg/ml. The developed method proved to be very selective, without interferences from other endogenous substances and the influences of possible coadministered drugs. The limits of detection and quantification estimated by the signal-to-noise ratio in real samples were 0.24 and 0.4 μg/ml, respectively. The developed method is simple and can be easily applied in clinics and emergency cardiac situations after the initial loading dose of TCG in the first few hours of a heart attack.

Topics: Acute Coronary Syndrome; Chromatography, High Pressure Liquid; Humans; Myocardial Infarction; Plasma; Platelet Aggregation Inhibitors; Ticagrelor

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

Ticagrelor is currently considered a first-line choice in dual antiplatelet therapy (DAPT) following revascularization of acute coronary syndrome (ACS). However, its use is correlated with an increased incidence of two side effects, dyspnea and bradyarrhythmias, whose molecular mechanisms have not yet been defined with certainty and, consequently, neither of the therapeutic decisions they imply. We report the case of a patient with acute myocardial infarction treated with ticagrelor and aspirin as oral antithrombotic therapy after primary percutaneous coronary intervention (PCI), manifesting in a significant bradyarrhythmic episode that required a switch of antiplatelet therapy. Starting from this case report, this article aims to gather the currently available evidence regarding the molecular mechanisms underlying these side effects and propose possible decision-making algorithms regarding their management in clinical practice.

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

Topics: Acute Coronary Syndrome; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Retrospective Studies; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

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

This study aimed to investigate the effects of ticagrelor on myocardial microcirculation, cardiac function, and adverse cardiovascular events in ST-segment elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention (PCI).. A total of 80 STEMI patients admitted to our hospital from February 2020 to March 2023 were selected and included in the retrospective study, all receiving PCI treatment. They were randomly and retrospectively divided into a control group (40 cases) and an observation group (40 cases), and treated with clopidogrel and ticagrelor, respectively. The clinical effects were compared.. The starting perfusion time of the contrast agent in the myocardial infarction area in the observation group was 2.22±0.27 s, and the peak perfusion time was 2.62±0.27 s, which was lower than those in the control group (2.51±0.29 s and 3.21±0.39 s, t=4.629, 7.867, p=0.000). The ratio of peak perfusion intensity between the two groups was significantly different (t=2.363, p=0.021). Left ventricular ejection fraction, stroke volume index, and cardiac index in the observation group were higher than those in the control group (55.03±6.03 vs. 52.33±5.13; 57.39±6.81 vs. 51.11±6.31 L/min·m-2; 3.49±0.45 vs. 3.12±0.38 mL/m2, t=2.157, 4.278, 3.973, p<0.05). The observation group had lower levels of brain natriuretic peptide and C-reactive protein compared to the control group (425.35±55.71 vs. 589.36±70.24 pg/mL; 15.13±1.03 vs. 21.64±2.74 mg/L; t=11.570, 14.066, p=0.000). There was no statistical significance in the incidence of adverse cardiovascular events between the two groups (2.50% vs. 7.50%, χ2=1.920, p=0.166).. The use of ticagrelor can regulate myocardial microcirculation and improve cardiac function in STEMI patients undergoing PCI.

Topics: Humans; Microcirculation; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Retrospective Studies; ST Elevation Myocardial Infarction; Stroke Volume; Ticagrelor; Treatment Outcome; Ventricular Function, Left

To investigate whether use of ticagrelor compared to clopidogrel is associated with different risks for thrombotic events or major bleeding among acute myocardial infarction (AMI) patients with a prior history of acute ischemic stroke.. This retrospective cohort study used the Health and Welfare Database in Taiwan. Stroke patients prescribed ticagrelor plus aspirin or clopidogrel plus aspirin after a primary hospitalization for AMI between July 1, 2013, and December 31, 2018, were included. Inverse probability of treatment weighting was applied to balance covariates between treatment groups. The primary effectiveness outcome included a composite measure of AMI, acute ischemic stroke, or all-cause mortality. The primary safety outcome included a composite measure of intracranial hemorrhage (ICH) and major gastrointestinal bleeding. The secondary effectiveness and safety outcomes comprised each of the individual components that make up the primary effectiveness and safety outcomes, respectively.. A total of 1691 eligible patients were included in the study, of whom 734 (43.4%) received ticagrelor plus aspirin and 957 received clopidogrel plus aspirin. There were no significant differences observed in the primary and secondary effectiveness outcomes between the two study groups. However, the use of ticagrelor was associated with a higher risk of ICH (ticagrelor: 8.68 per 1000 person-year; clopidogrel: 2.17 per 1,000 person-year; HR, 3.34; 95% CI, 1.27 to 8.81, P = .01) compared with clopidogrel.. In AMI patients with a history of acute ischemic stroke, the risks of cardiovascular events were comparable between ticagrelor plus aspirin and clopidogrel plus aspirin. However, ticagrelor was associated with a higher risk of ICH. Ticagrelor should be used cautiously in AMI patients with a history of acute ischemic stroke.

Topics: Aspirin; Clopidogrel; Humans; Ischemic Stroke; Myocardial Infarction; Platelet Aggregation Inhibitors; Retrospective Studies; Ticagrelor

Mild therapeutic hypothermia (MTH) is believed to reduce the effectiveness of antiplatelet drugs. Effective dual-antiplatelet therapy after percutaneous coronary intervention (PCI) is mandatory to avoid acute stent thrombosis. The effectiveness of ticagrelor in MTH-treated out-of-hospital cardiac arrest (OHCA) survivors is still a matter of debate. The aim of the study was to evaluate the impact of MTH on the platelet-inhibitory effect of ticagrelor in comatose survivors of OHCA treated with primary PCI.. Eighteen comatose survivors of OHCA with acute coronary syndrome undergoing immediate PCI treated with MTH were compared with 14 patients with uncomplicated primary myocardial infarction after PCI, matched for gender and age, in a prospective, single-center, observational study. Platelet aggregation was evaluated using VerifyNow P₂Y₁₂ point-of-care testing at 3 time points: admission (T₀), during MTH (T₁), and 48-72 h after rewarming (T₂).. Ticagrelor effectively inhibits platelet aggregation in OHCA patients subjected to MTH and in all patients in the control group. The effectiveness of ticagrelor did not differ between the MTH group and the control group (p = 0.581). In 2 cases in the MTH population, the platelet response to ticagrelor was inadequate, and in one of them it remained insufficient during the re-warming phase. There was no stent thrombosis in these patients.. The present study confirmed the effectiveness of ticagrelor to inhibit platelets in myocardial infarction patients after OHCA treated with primary PCI undergoing hypothermia. The use of cooling was not associated with an increased risk of stent thrombosis.

Topics: Coma; Humans; Hypothermia, Induced; Myocardial Infarction; Out-of-Hospital Cardiac Arrest; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Prospective Studies; Ticagrelor

To examine methodologies that address imbalanced treatment switching and censoring, 6 different analytical approaches were evaluated under a comparative effectiveness framework: intention-to-treat, as-treated, intention-to-treat with censor-weighting, as-treated with censor-weighting, time-varying exposure, and time-varying exposure with censor-weighting. Marginal structural models were employed to address time-varying exposure, confounding, and possibly informative censoring in an administrative data set of adult patients who were hospitalized with acute coronary syndrome and treated with either clopidogrel or ticagrelor. The effectiveness endpoint included first occurrence of death, myocardial infarction, or stroke. These methodologies were then applied across simulated data sets with varying frequencies of treatment switching and censoring to compare the effect estimate of each analysis. The findings suggest that implementing different analytical approaches has an impact on the point estimate and interpretation of analyses, especially when censoring is highly unbalanced.

Topics: Acute Coronary Syndrome; Adult; Aged; Clopidogrel; Comparative Effectiveness Research; Computer Simulation; Female; Hospitalization; Humans; Intention to Treat Analysis; Latent Class Analysis; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Selection Bias; Stroke; Ticagrelor; Treatment Outcome; Treatment Switching

Topics: Asian People; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Ticagrelor

To assess, in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous intervention, the pace of introduction in clinical practice (2010-2017) of drug-eluting stents (DES), ticagrelor, prasugrel, and prolonged dual antiplatelet therapy (DAPT) duration, and their potential impact on the risk of 2-year outcomes.. Prospective and exhaustive community-wide cohort of 14 841 STEMI patients undergoing primary percutaneous intervention between 2010 and 2017. Index episodes were obtained from the Catalan Codi IAM Registry, events during follow-up from the Minimum Data Set and DAPT were defined by pharmacy dispensation. Follow-up was 24 months. The temporal trend for exposures and outcomes was assessed using regression models.. Age> 65 years, diabetes, renal failure, previous heart failure, and need for anticoagulation at discharge were more frequent in later periods (P <.001). From 2010 to 2017, the use of DES increased from 31.1% to 69.8%, ticagrelor from 0.1% to 28.6%, prasugrel from 1.5% to 23.8%, and the median consecutive months on DAPT from 2 to 10 (P <.001 for all). Adjusted analysis showed a temporal trend to a lower risk of the main outcome over time: the composite of death, acute myocardial infarction, stroke and repeat revascularization (absolute odds reduction 0.005% each quarter; OR, 0.995; 95%CI, 0.99-0.999; P=.028). The odds of all individual components except stroke were reduced, although significance was only reached for revascularization.. Despite a strong increase between 2010 and 2017 in the use and duration of DAPT and the use of ticagrelor, prasugrel and DES, there was no substantial reduction in major cardiovascular outcomes.

Topics: Aged; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; ST Elevation Myocardial Infarction; Stroke; Ticagrelor; Treatment Outcome

Transcarotid artery revascularization (TCAR) with dynamic flow reversal is a hybrid technique for operative management of carotid artery stenosis. Dual antiplatelet therapy is recommended for patients undergoing TCAR; however, nonresponders to these medications may be predisposed to perioperative thromboembolic complications. Prevalent in up to 44% to 66% of patients taking clopidogrel, high on-treatment platelet reactivity may thus be responsible for a portion of adverse cerebrovascular events in TCAR. A previous single-institution study has demonstrated the use of ticagrelor as a viable alternative to clopidogrel for antiplatelet therapy in patients undergoing TCAR; however, large-scale comparisons between clopidogrel and ticagrelor are needed to confirm the safety of ticagrelor outside of highly selected patients and providers.. Data from patients enrolled in the Society for Vascular Surgery Vascular Quality Initiative undergoing TCAR with a perioperative antiplatelet therapy regimen including either clopidogrel or ticagrelor from January 2015 to March 2021 were analyzed and compared. Multivariable logistic regression and propensity score matching were used to evaluate the primary 30-day outcomes of stroke, major bleeding event, and combined stroke/myocardial infarction (MI)/death rate while adjusting for baseline characteristics of the patients.. A total of 11,973 patients underwent TCAR with a dual antiplatelet therapy regimen that included clopidogrel vs 426 patients with ticagrelor. Compared with patients on clopidogrel, patients on ticagrelor were significantly more likely to have coronary artery disease (51% vs 66%; P < .001), particularly unstable angina or MI within 6 months (3% vs 9%; P < .001), and more likely to have insulin-dependent diabetes mellitus (14% vs 19%; P < .001). The unadjusted 30-day rates of stroke, major bleeding, and combined stroke/MI/death were not statistically significant among both groups (1.3% vs 0.5%; P = .14, 2.4% vs 1.4%; P = .18, and 1.9% vs 1.6%; P = .71], respectively). After multivariable adjustment and propensity matching, these remained statistically insignificant.. Despite a substantially higher medical risk in patients undergoing TCAR with ticagrelor, 30-day rates of stroke, major bleeding events, and combined stroke/MI/death were similar between patients on ticagrelor and clopidogrel as part of adjunctive antiplatelet therapy. Randomized prospective trials, and studies with larger sample sizes and longer follow-up will be needed to better examine the outcome differences in TCAR between these two medications.

Topics: Clopidogrel; Endovascular Procedures; Femoral Artery; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Prospective Studies; Retrospective Studies; Risk Assessment; Risk Factors; Stents; Stroke; Ticagrelor; Time Factors; 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

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

Ticagrelor or prasugrel are recommended to reduce ischemic events in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). However, in clinical practice, patients are often switched from a potent P2Y12 inhibitor to clopidogrel prior to or at discharge ('de-escalation'). We sought to assess the incidence and predictors of de-escalation.. Consecutive patients who received either a ticagrelor or prasugrel loading dose for AMI PCI at two tertiary centers between Jan 2015-Mar 2019 who survived to discharge were included. Data were obtained from the electronic health record and institutional NCDR CathPCI data. Patients who were de-escalated to clopidogrel were compared with those who remained on potent P2Y12 inhibitors through the time of discharge.. Of the1818 patients in the cohort, 1146 (63%) were de-escalated. Patients in the de-escalation group were older, more often Black, had lower prevalence of co-morbidities, less often had private insurance, and had less complex PCI. After adjustment, older age remained positively associated (OR 1.2, CI 1.08-1.34, p = .001) and Caucasian race (OR 0.5, CI 0.33-0.77, p = .002), prior MI (OR 0.7, CI 0.5-0.97, p = .032), bifurcation lesion (OR 0.71, CI 0.53-0.95, p = .019), and greater number of stents (OR 0.82, CI 0.75-0.91, p = .0001) were negatively associated with de-escalation. In de-escalated patients, the rationale was not documented in 75.9% of cases.. De-escalation occurred frequently in patients with AMI and was associated with both non-clinical and clinical factors. Medical decision making was poorly documented and represent an area for improvement.

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

To explore the clinical efficacy of tirofiban combined with ticagrelor and aspirin in acute myocardial infarction treatment by percutaneous coronary intervention and its effect on patients' cardiac function.. We selected 102 patients with acute myocardial infarction who came to The First Hospital of LanZhou University for treatment from July 2018 to May 2021. On the basis of conventional treatment, patients were separated into a joint group (tirofiban combined with ticagrelor and aspirin) comprising 55 cases and a control group (conventional ticagrelor and aspirin dual treatment) involving 47 cases. Blood flow classification of the two groups of patients was immediately recorded and compared after the myocardial infarction thrombolysis test (TIMI). Left ventricular function-related indicators, platelet-related parameters, neutrophil/lymphocyte ratio (NLR), red blood cell distribution width (RDW), and platelet/lymphocyte ratio (PLR) before treatment and 7 days after PCI were evaluated and compared between the groups before treatment and 3 months after treatment. ELISA was utilized to detect the serum levels of inflammatory factors, tumor necrosis factor-

Topics: Aspirin; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Tirofiban; Treatment Outcome

Kim CJ, Park MW, Kim MC, et al.

Topics: Clopidogrel; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; 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

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

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

Introduction: In patients who have survived myocardial infarction, platelet aggregation inhibitor (TAG) treatment plays an important role in preventing recurrent ischemic events. Objective: to investigate the proportion of patients who received aspirin, clopidogrel, prasugrel and ticagrelor during the hospitalization and the proportion of patients who continued taking the recommended therapy during follow-up. All patients treated for myocardial infarction who had a medical ID number were included in the study. Results: 16 273 patients had ST-elevation (STEMI) and 20 305 patients had non-ST-elevation (NSTEMI) infarction. 80% of patients were hypertensive. Diabetes mellitus (35%) and impaired renal function (30%) were demonstrated in one in three patients. The TAG treatment recommendation was analysed in 36 578 patients who left the hospital. Clopidogrel 12.7%, prasugrel 4.3%, ticagrelor, 93.9%, 77.7%, 8.3% and 3.2% were found in the NSTEMI group. For medicines available under special conditions (prasugrel, ticagrelor), there were significant differences between cen­tres: the proposal varied between 1.2–4.3% for prasugrel and 0.3–10.8% for ticagrelor. Drug switching events were monitored using the National Institute of Health Insurance Fund database. Pharmacovigilance data were available for 29 405 patients. We considered the longest period in the adherence study, and the grace period was 2 months. Adherence durations were processed using a standard survival analysis toolkit (Kaplan–Meier method). At 1 year after the first switch, 76.1%, 78.3%, and 80.9% of the patients in clopidogrel, prasugrel and ticagrelor were adherents to the recommended treatment. Conclusion: The frequency of use of certain antiplatelet drugs varies significantly across different intervention centres. More than three-quarters of the patients are adherent to treatment 1 year after starting treatment.. Összefoglaló. Bevezetés: Szívinfarktust túlélt betegeknél a thrombocytaaggregáció-gátló (TAG-) kezelésnek fontos szerepe van az újabb ischaemiás események megelőzése szempontjából. Célkitűzés: Annak vizsgálata, hogy a kórházi távozás idején a betegek milyen arányban részesültek clopidogrel-, prasugrel- és ticagrelorkezelésben, és az utánkövetés ideje alatt milyen arányban folytatták a javasolt terápiát. Módszer: A Nemzeti Szívinfarktus Regiszter adatbázisában 2018. 01. 01. és 2020. 12. 31. között 39 308 olyan, infarktus miatt kezelt beteget tartottunk nyilván, aki egészségügyi azonosító számmal rendelkezett, és szívkatéteres centrumban kapott ellátást. Eredmények: 16 273 betegnél ST-elevációval (STEMI), 20 305 betegnél ST-elevációval nem járó (NSTEMI) infarktus volt. A betegek 80%-a hypertoniás volt, minden harmadik betegnél diabetes mellitus (35%), illetve csökkent vesefunkció (30%) igazolódott. A kórházból távozó betegek 36 578 infarktusos eseményénél elemeztük a távozáskor adott TAG-kezelési javaslatot. A STEMI-betegek 96,2%-a aszpirin-, 78,3%-a clopidogrel-, 12,7%-a prasugrel- és 4,3%-a ticagrelorkezelési javaslatot kapott. Az NSTEMI-betegcsoportban 93,9%, 77,7%, 8,3%, 3,2% értékeket találtuk. A speciális feltételek esetén rendelhető gyógyszerek (prasugrel, ticagrelor) esetén az egyes centrumok között jelentős különbségek voltak: a javaslat a prasugrel esetén 1,2–24,3%, a ticagrelor esetén 0,3–10,8% között változott. A Nemzeti Egészségbiztosítási Alapkezelő (NEAK) adatbázisának felhasználásával követtük a gyógyszerkiváltási eseményeket. A gyógyszertámogatási adatok 29 405 betegnél álltak rendelkezésre. Az adherencia vizsgálatakor a leghosszabb időszakot vettük figyelembe, és a türelmi idő 2 hónap volt. Az adherencia-időtartamokat standard túléléselemzési eszköztárral (Kaplan–Meier-féle eljárás) dolgoztuk fel. Az első gyógyszerkiváltást követő 1 évnél a clopidogrel, a prasugrel és a ticagrelor esetében a betegek 76,1%-a, 78,3%-a és 80,9%-a adherens volt a javasolt kezeléshez. Következtetés: Bizonyos TAG-gyógyszerek alkalmazásának gyakorisága jelentősen eltér a különböző intervenciós centrumokban. 1 évvel a kezelés megkezdése után a betegek több mint háromnegyede adherens a kezeléshez. Orv Hetil. 2022; 163(19): 743–749.

Topics: Clopidogrel; Humans; Hungary; Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; ST Elevation Myocardial Infarction; Ticagrelor

Background In clinical trials, cangrelor has been shown to reduce percutaneous coronary intervention-related ischemic complications without increasing major bleeding. This study was performed to examine cangrelor use and transition to oral P2Y

Topics: Adenosine Monophosphate; Clopidogrel; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Registries; Ticagrelor; Treatment Outcome

Patients with type-2 diabetes are twice as likely to suffer from acute myocardial infarction (AMI) and have a higher incidence of recurrent events than their non-diabetic counterparts. Ticagrelor is a platelet inhibitor known to reduce major adverse cardiovascular events (MACE) in AMI patients. This study measures the level and change in platelet activation and aggregation at the time of and following an AMI in patients with and without diabetes treated with ticagrelor.. Ninety-seven patients were prospectively enrolled (diabetes, N = 33; no diabetes, N = 64). No difference was observed in the expression of P-selectin and PAC-1 at any given point between diabetes and non-diabetes groups (p > 0.05). No difference was observed in the percentage of platelet bound to leukocytes at any measured timepoint between patients with and without diabetes (p > 0.05). Platelet leukocyte aggregation was suppressed during the acute phase compared to quiescence equally among both groups.. Ticagrelor demonstrated similar in-vivo effects on platelet activation and aggregation regardless of diabetes status in patients presenting with AMI.

Topics: Diabetes Mellitus, Type 2; Humans; Myocardial Infarction; P-Selectin; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; 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

Secondary prevention of cardiovascular events among patients with diagnosed cardiovascular disease and high ischemic risk poses a significant challenge in clinical practice. The combinations of aspirin with low-dose (LD) ticagrelor or LD rivaroxaban have shown superiority in preventing major adverse cardiovascular events (MACE) compared with aspirin treatment alone. The comparative value for money of these two regimens remains unexplored.. We analyzed each regimen's annual cost needed to treat (CNT) by multiplying the annualized number needed to treat (aNNT) by the annual cost of each drug. The aNNTs were based on outcome data from PEGASUS TIMI-54 and COMPASS trials. Scenario analyses were performed to overcome variances in terms of population risk. Costs were calculated as 75% of US National Average Drug Acquisition Cost (NADAC), extracted in January 2022. The primary outcome was defined as CNT to prevent one MACE across the two regimens. Secondary value analysis was performed for myocardial infarction (MI), stroke, and cardiovascular death as separate outcomes.. The aNNTs to prevent MACE with LD ticagrelor and with LD rivaroxaban were 229 [95% confidence interval (CI) 141-734] and 147 (95% CI 104-252), respectively. At an annual cost of US$3726 versus US$4533, the corresponding CNTs were US$853,254 (95% CI 525,366-2,734,884) with LD ticagrelor and US$666,351 (95% CI 471,432-1,142,316) with LD rivaroxaban.. Combining aspirin with LD rivaroxaban provides better value for money than with LD ticagrelor for secondary prevention of MACE.

Topics: Adenosine; Aspirin; Drug Therapy, Combination; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Rivaroxaban; Secondary Prevention; 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

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

Potent P2Y. The authors compared the efficacy and safety of ticagrelor and prasugrel in a real-world contemporary PCI cohort.. Consecutive patients undergoing PCI between 2014 and 2019 discharged on either prasugrel or ticagrelor were included from the prospectively collected institutional PCI registry. Primary endpoint was the composite of death and myocardial infarction (MI), with secondary outcomes including rates of bleeding, stroke, and target vessel revascularization at 1 year.. Overall, 3,858 patients were included in the study (ticagrelor: n = 2,771; prasugrel: n = 1,087), and a majority (48.4%) underwent PCI in the context of CCS. Patients prescribed ticagrelor were more likely to be female, have a history of cerebrovascular disease, and have ACS presentation, while those receiving prasugrel were more likely to be White with a higher prevalence of prior revascularization. No difference in the risk of death or MI was noted across the groups (ticagrelor vs prasugrel: 3.3% vs 3.1%; HR: 0.88; 95% CI: 0.54-1.43; P = 0.59). Rates of target vessel revascularization were significantly lower in the ticagrelor cohort (9.3% vs 14.0%; adjusted HR: 0.71; 95% CI: 0.55-0.91; P = 0.007) with no differences in stroke or bleeding. The results were consistent in patients with CCS (HR: 0.84; 95% CI: 0.46-1.54) and ACS (HR: 1.18; 95% CI: 0.46-1.54), without evidence of interaction (P = 0.37), and confirmed across multivariable adjustment and propensity score stratification analysis.. In this contemporary patient population undergoing PCI, prasugrel and ticagrelor were associated with similar 1-year efficacy and safety.

Topics: Acute Coronary Syndrome; Female; Humans; Male; Myocardial Infarction; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Stroke; Ticagrelor; Treatment Outcome

Ticagrelor is a frequently prescribed platelet aggregation inhibitor used in patients with acute coronary syndrome. A rare side effect is severe dyspnoea.. A 76 year old woman experiences severe shortness of breath three weeks after percutaneous coronary intervention because of acute myocardial infarction. Physical examination and additional investigation showed no pulmonary or cardiac explanation for her complaints. Shortly after cessation of ticagrelor, her complaints disappeared.. Ticagrelor-related severe dyspnoea in post-myocardial infarction patients is a diagnosis by exclusion of other reasonable causes of dyspnoea. Unfamiliarity with this side effect can lead to excess diagnostics and unnecessary referrals.

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

Ticagrelor and prasugrel are the mainstay of antithrombotic therapy for patients with acute myocardial infarction (MI). However, direct comparative data on clinical outcomes of potent P2Y12 inhibitors are limited, especially in East Asian populations. We aimed to evaluate the effect of ticagrelor versus prasugrel on clinical outcomes in patients with acute MI.. From the Korean nationwide National Health Insurance database, 10,797 patients with acute MI who received either ticagrelor or prasugrel in combination with aspirin after percutaneous coronary intervention (PCI) were enrolled. The primary outcome was net clinical benefit, defined as a composite of death, MI, stroke, or major bleeding. Secondary outcomes included the individual components of the primary outcome as effectiveness and safety measures.. Among 10,797 patients, 9591 (88.8%) received ticagrelor and 1206 (11.2%) received prasugrel. During a median follow-up of 1.8 years, the primary outcome occurred in 1051 (16.6%) and 131 (14.4%) patients in the ticagrelor and prasugrel groups, respectively. In the propensity score matched cohort (n = 5979), the risk for the primary outcome was similar between the two groups (hazard ratio [HR] 0.949 for prasugrel; 95% confidence interval [CI]: 0.780-1.154). The risks for the composite of death, MI, or stroke (HR 0.938; 95% CI: 0.752-1.169) and major bleeding (HR 1.022; 95% CI: 0.709-1.472) were also comparable.. In patients with acute MI undergoing PCI, ticagrelor and prasugrel appeared to have similar net clinical benefits. The risks for death, MI, or stroke and major bleeding were not significantly different between the two groups.

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

Ticagrelor is anantiplatelet agent which acts through reversible binding to the P2Y12 adenosine-diphosphate receptors. In acute coronary syndromes it has been shown to reduce the risk of major cardiovascular events such as myocardial infarction, stroke and death. Although some hemorrhagic, kidney, liver and respiratory complications have been described in detail with the use of ticagrelor, other less frequent adverse effects are not so well clarified. We report the case of a patient with a systemic inflammatory response syndrome secondary to the use of ticagrelor.. El ticagrelor es un antiagregante plaquetario que actúa a través de la unión reversible a los receptores P2Y12 de la adenosina-difosfato. En el síndrome coronario agudo, ha demostrado reducir el riesgo de eventos cardiovasculares mayores como infarto de miocardio, accidente cerebrovascular y muerte. Si bien se han descripto en detalle ciertas complicaciones hemorrágicas, renales, hepáticas y respiratorias por el uso del ticagrelor, otros efectos adversos menos frecuentes de la droga no han sido adecuadamente esclarecidos. Presentamos el caso de un paciente con un síndrome de respuesta inflamatoria sistémica secundario al uso de ticagrelor.

Topics: Acute Coronary Syndrome; Adenosine; Humans; Myocardial Infarction; Systemic Inflammatory Response Syndrome; Ticagrelor

Clinical outcomes are unknown after ticagrelor treatment in patients with end-stage renal disease (ESRD) who are diagnosed with acute myocardial infarction (AMI). ESRD patients who were on hemodialysis and received dual antiplatelet therapy (DAPT) for AMI between July 2013 and December 2016 were identified in Taiwan's National Health Insurance Research Database. Using stabilized inverse probability of treatment weighting, patients receiving aspirin plus ticagrelor (n = 530) were compared with those receiving aspirin plus clopidogrel (n = 2462) for the primary efficacy endpoint, a composite of all-cause death, nonfatal myocardial infarction, or nonfatal stroke, and bleeding, defined according to the Bleeding Academic Research Consortium. Study outcomes were compared between the two groups using Cox proportional hazards model or competing risk model for the hazard ratio or subdistribution hazard ratio (SHR). During 9 months of follow-up, ticagrelor was comparable to clopidogrel with respect to the risks of primary efficacy endpoint [11.69 vs. 9.28/100 patient-months; SHR, 1.16; 95% confidence interval (CI) 0.97-1.4] and bleeding (5.55 vs. 4.36/100 patient-months; SHR 1.14; 95% CI 0.88-1.47). In conclusion, among hemodialysis patients receiving DAPT for AMI, ticagrelor was comparable to clopidogrel with regard to the composite efficacy endpoint and bleeding.

Topics: Aged; Clopidogrel; Cohort Studies; Female; Humans; Kidney Failure, Chronic; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Renal Dialysis; 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

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

Periprocedural myocardial infarction is a common complication following percutaneous coronary intervention. The present study was conducted with an aim to compare the safety and efficacy of loading doses of ticagrelor versus clopidogrel in preventing periprocedural myocardial infarction in Asian patients with acute coronary syndrome undergoing elective percutaneous coronary intervention.. A total of 114 patients with acute coronary syndrome undergoing elective percutaneous coronary intervention were assigned to clopidogrel group (n = 57, the loading and maintenance doses were 300 and 75 mg qd for clopidogrel, and 300 and 100 mg qd for aspirin), or ticagrelor group (n = 57, the loading and maintenance doses were 180 and 90 mg bid for ticagrelor, and 300 and 100 mg qd for aspirin). Cardiac biomarkers were measured before, 8 hours, and 24 hours after percutaneous coronary intervention. The percutaneous coronary intervention-related periprocedural myocardial infarction was defined according to the fourth universal definition of myocardial infarction (2018).. The overall incidence of percutaneous coronary intervention-related periprocedural myocardial infarction was 21.1%. The ticagrelor group showed a significantly lower incidence of periprocedural myocardial infarction (12.3% vs 29.8%, p = 0.022) and numerically lower bleeding events (3.5% vs 8.8%, p = 0.242) as compared with clopidogrel group. No patient had major adverse cardiovascular events during the 1-month follow-up. The levels of high-sensitivity C-reactive protein did not differ significantly between the two groups (p > 0.05), indicating that the benefits of ticagrelor were not from its anti-inflammatory effects. Multivariable analysis showed that the use of ticagrelor (odds ratio: 0.50; 95% confidence interval: 0.29-0.87; p = 0.014) and number of stents (odds ratio: 2.75; 95% confidence interval: 1.25-6.06; p = 0.012) were independent predictors of periprocedural myocardial infarction.. Pretreatment with a loading dose of ticagrelor seems to be superior in reducing the incidence of percutaneous coronary intervention-related periprocedural myocardial infarction in Asian patients with acute coronary syndrome as compared with clopidogrel.

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

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

To investigate the effects of early upstream antithrombotic therapy administration (ATTA) in ST-segment elevation myocardial infarction (STEMI) patients with prolonged transport times to primary percutaneous intervention (PPCI) on major clinical outcomes.. It remains unclear whether early upstream administration of aspirin, ticagrelor, and unfractionated heparin (UFH) confers additional benefits compared with in-hospital administration.. Between 2015 and 2018, we performed PPCI in 709 included consecutive STEMI patients. We compared 482 STEMI patients who received aspirin, ticagrelor, and UFH loading in a non-PCI capable spoke hospital before transfer (NPHT) versus 227 prehospital triage setting (PTS) STEMI patients who received in-ambulance aspirin, followed by ticagrelor and UFH in the hub catheterization laboratory. The primary outcome was the presence of a pre-PPCI TIMI flow 2-3 in the infarct related artery (IRA). The secondary outcomes included definite acute stent thrombosis and hemorrhagic complications.. The median times from ticagrelor and heparin administration to angiography in the NPHT group and the PTS group were 80.5 min (Interquartile Range (IQR) 68.5-94) and 10 min (IQR 5-15) respectively (p < .0001). Using inverse probability of treatment weighting to minimize heterogeneity between groups, we showed significant differences for the primary outcome (44.6 versus 18.5%, p < .0001) and for definite acute stent thrombosis (0.6 versus 2.6%, p = .03), with no difference in the combined in-hospital BARC 2-5 bleeding events (1.9 versus 3.5%, p = .18) in the NPHT versus the PTS group, respectively.. In this single-center retrospective cohort study, after adjusting for baseline covariates, early upstream ATTA with aspirin, ticagrelor, and UFH was associated with greater pre-PPCI TIMI flow and less definite acute stent thrombosis in STEMI patients, without increased bleeding risk.

Topics: Aspirin; Heparin; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Retrospective Studies; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

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

The current article describes a 72-year-old woman who suffered an acute myocardial infarction due to plaque erosion (PE) 2 weeks after abemaciclib treatment onset due to advanced breast cancer. Abemaciclib is a cyclin-dependent kinase 4 and 6 inhibitor that has recently demonstrated efficacy and safety in advanced breast cancer. Of major concern, however, reported thromboembolic rates in randomized clinical trials testing this drug range from 0.6 to 5%. To the best of our knowledge this is the first thrombotic coronary side effect ever reported. We suggest that a treatment that increases thromboembolic risk, such abemaciclib, may have triggered PE in our patient, 15 days after abemaciclib initiation. New molecules are promising in cancer treatment; however, care must be paid to their potential cardiotoxic effects.

Topics: Aged; Aminopyridines; Antineoplastic Agents; Artifacts; Benzimidazoles; Breast Neoplasms; Coronary Vessels; Enoxaparin; Female; Humans; Lipids; Myocardial Infarction; Protein Kinase Inhibitors; Thromboembolism; Ticagrelor; Treatment Outcome

A 41-year-old woman with chest pain for 6 hours was admitted to our chest pain center, presenting with acute myocardial infarction. Coronary angiography showed acute total occlusion in the proximal left anterior descending artery due to late stent thrombosis. After thrombus aspiration and intracoronary administration of 0.5 mg tirofiban, repeated angiography showed that no obvious residual stenosis remained. The patient underwent drug-coated balloon angioplasty 69 days ago and was then administered dual antiplatelet treatment (aspirin and clopidogrel) uninterruptedly. Genetic testing found that both cytochrome P450 2C19 (CYP2C19) (G681A) and glycoprotein Ia (GPIa) (C807T, G873A) were hybrid mutant types, demonstrating that the patient was possibly resistant to clopidogrel and aspirin simultaneously. Thus, clopidogrel was replaced by ticagrelor and no more cardiovascular adverse events occurred during the 2-year follow-up.

Topics: Acute Disease; Adult; Aftercare; Angioplasty, Balloon, Coronary; Aspirin; Clopidogrel; Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Cytochrome P-450 CYP2C19; Dual Anti-Platelet Therapy; Female; Fibrinolytic Agents; Humans; Integrin alpha2; Mutation; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Stents; Thrombectomy; Thrombosis; Ticagrelor; Tirofiban; Treatment Outcome

To examine the effect of de-escalation of P2Y12 inhibitor in dual antiplatelet therapy (DAPT) on major adverse cardiovascular events (MACE) and bleeding complications after acute myocardial infarction (AMI) in Taiwanese patients undergoing percutaneous coronary intervention (PCI). Patients who had received PCI during hospitalization for AMI (between 2013 and 2016) and were initially treated with aspirin and ticagrelor and without adverse events after 3 months of treatment were retrospectively evaluated. In total, 1,901 and 8,199 patients were identified as "de-escalated DAPT" (switched to aspirin and clopidogrel) and "unchanged DAPT" (continued on aspirin and ticagrelor) cohorts, respectively. With a mean follow-up of 8 months, the incidence rates (per 100 person-year) of death, AMI readmission and MACE were 2.89, 3.68, and 4.91 in the de-escalated cohort and 2.42, 3.28, and 4.72 in the unchanged cohort, respectively, based on an inverse probability of treatment weighted approach that adjusting for baseline characteristics of the patients. Multivariate Cox regression analyses showed the two groups had no significant differences in the hazard risk of death, AMI admission, and MACE. Additionally, there was no observed difference in the risk of bleeding, including major or clinically relevant non-major bleeding. The real-world data revealed that de-escalation of P2Y12 inhibitor in DAPT was not associated with a higher risk of death or AMI readmission in Taiwanese patients with AMI undergoing successful PCI.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aspirin; Clopidogrel; Drug Substitution; Dual Anti-Platelet Therapy; Humans; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Ticagrelor; Young Adult

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

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

溃疡性结肠炎患者通常处于高凝状态且存在消化道出血，若同时合并急性心肌梗死则在药物及介入治疗方面存在诸多矛盾，通常预后较差，目前尚无公认的最佳治疗方案。该文报道1例重度活动性溃疡性结肠炎合并消化道出血的患者，院内发生急性下壁心肌梗死合并交界性心律及低血压，行急诊经皮冠状动脉介入治疗，于右冠状动脉病变行血栓抽吸及球囊扩张。术后予替格瑞洛90 mg（2次/d）抗血小板单药治疗，随访14个月无心绞痛发作，未出现便血加重。.

Topics: Acute Coronary Syndrome; Colitis, Ulcerative; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Observational studies comparing ticagrelor and prasugrel in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) have yielded contradictory results, but these studies often did not consider differential censoring (eg, for treatment switching or insurance disenrollment) or confounding by time-dependent factors.. Our objective was to conduct a comparative effectiveness and safety analysis of ticagrelor and prasugrel in patients who underwent PCI after being hospitalized for an ACS.. This study used the Optum's de-identified Clinformatics. Included in the analysis were 2559 patients initiated on ticagrelor and 4456 patients initiated on prasugrel following PCI. Patients initiated on ticagrelor were 10% more likely to have eligibility disenrollment (Ticagrelor: 57%, Prasugrel: 47%, p < 0.01) and 7 percentage-points more likely to switch medication (Ticagrelor: 35%, Prasugrel: 28%, p < 0.01). After adjusting for multiple factors, including time-varying exposure and censoring imbalance, ticagrelor was associated with a higher risk of all-cause death, MI, or stroke when compared to prasugrel (Hazard ratio (HR): 1.33; 95% CI: 1.04-1.68). Similarly, ticagrelor was associated with a higher risk in bleeding events when compared with prasugrel (HR: 1.61; 95% CI: 1.19-2.17).. When compared with ticagrelor, prasugrel use following PCI for ACS was associated with a lower risk of death, MI, or stroke, as well as a reduced risk of major bleeding.

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

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

Topics: Adverse Drug Reaction Reporting Systems; Decision Support Techniques; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Primary Prevention; Purinergic P2Y Receptor Antagonists; Risk Assessment; Stroke; Ticagrelor; United States; United States Food and Drug Administration

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

"Ad hoc" percutaneous coronary intervention (PCI) is a frequent practice as reported in large real-life registries, but most of the patients undergo PCI without being on full and effective dual antiplatelet therapy or clopidogrel is administered orally only a few minutes before the beginning of the procedure. This practice, especially in complex PCI, could be affected by a higher rate of peri-procedural adverse events.. We present the case of a 72-year old male diabetic, hypertensive and hyperlipidemic, clopidogrel-naïve, with stable angina who underwent coronary angiography showing several tight stenoses on the left descending artery (LAD) and followed by a chronic total occlusion (CTO) of the vessel. The two main diagonal branches were severely stenosed at the origin as well. Due to patient's decision an ad hoc complex PCI (CTO and multiple Bifurcations) was successfully performed using cangrelor, instead of cath-lab clopidogrel pretreatment, in order to reduce the incidence of peri-procedural myocardial infarction risk, as suggested by recent evidence. Finally, the patient was started on dual antiplatelet therapy with ticagrelor, as guidelines recommend to consider in complex procedures, and discharged 48 h later without complications or significant increases of myocardial enzymes.. Current Guidelines recommend loading dose (I/A) or pre-treatment with clopidogrel, nevertheless trials have not demonstrated its benefit, unlike cangrelor. This case highlights the role of aggressive antiplatelet therapy administered in the cath lab to reduce periprocedural ischemic events during elective treatment of complex lesions requiring multiple stenting in clopidogrel-naïve patients.

Topics: Aged; Clopidogrel; Humans; Male; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

We evaluated the effect of ticagrelor monotherapy on outcomes after multiple arterial grafting (MAG) or single arterial grafting (SAG) in coronary artery bypass grafting (CABG).. In a post hoc, non-randomized analysis of the TiCAB (Ticagrelor in CABG; ClinicalTrials.gov NCT01755520) trial, we compared event rates for ticagrelor versus aspirin in patients undergoing MAG and SAG. Primary outcome was the composite of cardiovascular death, non-fatal myocardial infarction (MI), stroke or repeat revascularization 1 year after CABG. Secondary outcomes included individual components of the primary end point, all-cause death and bleeding.. Among 1753 patients, 998 patients underwent MAG and 755 patients underwent SAG. There was no significant difference in the 1-year primary composite outcome for ticagrelor versus aspirin with MAG [7.2% vs 7.9%; hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.57-1.43; P = 0.66] or SAG (12.3% vs 8.6%; HR 1.47, 95% CI 0.93-2.31; P = 0.10). Event rates for cardiovascular death, MI, stroke, repeat revascularization and all-cause death were similar for both treatment groups with MAG and SAG. No significant difference in major bleeding was observed for ticagrelor versus aspirin with MAG (2.6% vs 2.7%; HR 0.95, 95% CI 0.44-2.05; P = 0.90) or SAG (5.8% vs 4.0%; HR 1.49, 95% CI 0.77-2.89; P = 0.24).. In patients undergoing either MAG or SAG in the TiCAB trial, ticagrelor monotherapy compared with aspirin did not affect the rate of cardiovascular death, non-fatal MI, stroke or repeat revascularization, or the rate of bleeding, at 1 year after CABG.

Topics: Aspirin; Coronary Artery Bypass; Coronary Artery Disease; Humans; Myocardial Infarction; Stroke; Ticagrelor; Treatment Outcome

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: Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Secondary Prevention; Ticagrelor

Topics: Humans; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; NF-kappa B; Ticagrelor

ACC/AHA guidelines support the use of the P2Y. Multicenter, longitudinal analysis of patients and hospitals in the National Cardiovascular Data Registry (NCDR) Chest Pain - MI Registry from the third quarter of 2013 to the first quarter of 2017.. A total of 362,354 AMI patients treated at 801 hospitals were included in our analysis. Ticagrelor use increased over time, from 6.1% in 2013 to 33.7% in 2017, with corresponding reductions in the use of clopidogrel and prasugrel (p < 0.001 for all trends). In multivariable models, patients of white race, with private insurance, or STEMI were more likely to receive ticagrelor (p < 0.05 for all). Hospitals in the highest quartile of ticagrelor uptake had use rates ranging from 29% to 88%, and were more likely to have the lowest volume of MI patients. The correlation between prasugrel and ticagrelor adoption was weakly positive (correlation coefficient: 0.15, p = 0.004); hospitals with the lowest early adoption of prasugrel started with the lowest rate of ticagrelor use and had the slowest rate of increase in ticagrelor use.. There has been a rapid increase in use of ticagrelor since its approval by the FDA and both patient and hospital characteristics were associated with variation in its adoption and utilization. Further examination of the characteristics associated with the rapid adoption of new evidence may provide insights about improving health system performance.

Topics: Chest Pain; Hospitals; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Registries; Ticagrelor; Treatment Outcome

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

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

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

Topics: Betacoronavirus; Coronavirus Infections; COVID-19; Humans; Myocardial Infarction; Pandemics; Platelet Aggregation Inhibitors; Pneumonia, Viral; SARS-CoV-2; Ticagrelor

Topics: Aged; Aspirin; Bacteria; Case-Control Studies; Dual Anti-Platelet Therapy; Female; Gastrointestinal Microbiome; Humans; Intestines; Male; Methylamines; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recurrence; Risk Assessment; Risk Factors; Secondary Prevention; Stroke; Thrombosis; Ticagrelor; Time Factors; Treatment Outcome; United States; Up-Regulation

Treatment with newer direct-acting anti-platelet drugs (Ticagrelor and Prasugrel) prior to primary percutaneous coronary intervention (PCI) is associated with improved outcome in patients with ST-segment elevation myocardial infarction (STEMI) when compared with Clopidogrel. We compared infarct size following treatment with Ticagrelor/Prasugrel versus Clopidogrel in the DANish trial in Acute Myocardial Infarction (DANAMI-3) population of STEMI patients treated with primary PCI.. Patients were loaded with Clopidogrel, Ticagrelor or Prasugrel in the ambulance before primary PCI. Infarct size and myocardial salvage index were calculated using cardiac magnetic resonance (CMR) during index admission and at three-month follow-up. Six-hundred-and-ninety-three patients were included in this analysis. Clopidogrel was given to 351 patients and Ticagrelor/Prasugrel to 342 patients. The groups were generally comparable in terms of baseline and procedural characteristics. Median infarct size at three-month follow-up was 12.9% vs 10.0%, in patients treated with Clopidogrel and Ticagrelor/ Prasugrel respectively (p < 0.001), and myocardial salvage index was 66% vs 71% (p < 0.001). Results remained significant in a multiple regression model (p < 0.001).. Pre-hospital loading with Ticagrelor or Prasugrel compared to Clopidogrel, was associated with smaller infarct size and larger myocardial salvage index at three-month follow-up in patients with STEMI treated with primary PCI.

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

To investigate the long-term clinical benefit of dual antiplatelet therapy with potent P2Y12 inhibitors compared to clopidogrel in patients with acute coronary syndrome (ACS).. In this prospective multicenter observational study, we enrolled 708 patients with ACS treated with clopidogrel (n = 137), ticagrelor (n = 260) or prasugrel (n = 311). Major adverse cardiac events (MACE; over 1 year) and long-term mortality (median: 5.6 years; interquartile range [IQR] 4.9-6.5 years) were assessed. Multiple electrode aggregometry (MEA) was used to measure adenosine diphosphate (ADP)- and arachidonic acid (AA)-induced platelet aggregation.. Type of P2Y12 inhibitor emerged as an independent predictor of long-term mortality and MACE: patients treated with potent platelet inhibitors prasugrel or ticagrelor were at lower risk for long-term mortality (adjusted hazard ratio [HR] = 0.44; 95% CI: 0.22-0.92; P = .028) or MACE (adjusted HR = 0.38; 95% CI: 0.20-0.73; P = .004) than those treated with clopidogrel independent from clinical risk factors. In contrast, the efficacy of clopidogrel decreased with increasing severity of ACS: platelet aggregation was 37% higher in patients with ST segment elevation myocardial infarction (STEMI) and 25% higher in patients with non-ST elevation myocardial infarction (non-STEMI) compared to patients with unstable angina (P = .039). Patients with diabetes achieved less potent ADP- and AA-induced platelet inhibition under clopidogrel, compared to patients without diabetes (P = .045; P = .030, respectively).. In the setting of ACS, treatment with ticagrelor or prasugrel reduced long-term mortality and 1-year MACE as compared to clopidogrel.

Topics: Acute Coronary Syndrome; Adenosine Diphosphate; Aged; Arachidonic Acid; Aspirin; Cardiovascular Diseases; Clopidogrel; Dual Anti-Platelet Therapy; Female; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Prognosis; Proportional Hazards Models; Prospective Studies; Secondary Prevention; Stroke; Survival Rate; 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

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

Topics: Aged; Clopidogrel; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; 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

To investigate the therapeutic effects of ticagrelor and clopidogrel on patients with acute myocardial infarction (AMI) and its effect of lncRNA BANCR.. A total of 169 AMI patients admitted to our hospital from June 2015 to July 2018 were prospectively selected, of which 82 patients treated with clopidogrel were enrolled in the clopidogrel group (CG) and 87 patients treated with ticagrelor were enrolled in the ticagrelor group (TG). The therapeutic effect, serum lncRNA BANCR, platelet count, maximum platelet aggregation rate, serum troponin Ⅰ (cTnI), serum creatine kinase isoenzyme (CK-MB), and serum high sensitivity C-reactive protein (hs-CRP) levels of the two groups of patients were detected and compared before and after treatment. The incidence of adverse reactions (ADR) and the occurrence of major adverse cardiovascular events (MACE) within 6 months after treatment were recorded and compared, and the predictive value of BANCR on therapeutic effect and MACE occurrence was analyzed.. The therapeutic effect of TG was remarkably better than that of CG (p<0.05), and the improvement of serum BANCR, platelet count, maximum platelet aggregation rate, cTnⅠ, CK-MB, hs-CRP levels of the TG were remarkably better than that of CG (p<0.05). The incidence of ADR and MACE in the TG were notably lower than the CG (p<0.05). The expression of BANCR in the serum of patients with better therapeutic effect was significantly lower than that of patients with invalid treatment (p<0.05). The expression of BANCR in the serum of patients without MACE was significantly lower than that of patients with MACE (p<0.05). BANCR had high predictive value for both therapeutic effect and occurrence of MACE.. The effect of ticagrelor on AMI patients is significantly better than clopidogrel, and has higher safety. It can effectively reduce the content of BANCR in the serum of AMI patients, which is worthy of further promotion in clinical practice. Moreover, the predictive value of BANCR for the efficacy of AMI patients and the occurrence of MACE was high.

Topics: Acute Disease; Aged; Clopidogrel; Female; Humans; Male; Middle Aged; Myocardial Infarction; RNA, Long Noncoding; Ticagrelor

Out-of-hospital cardiac arrest (OHCA) frequently occurs in the early phase of acute myocardial infarction (MI). Survivors require percutaneous coronary intervention (PCI) with concomitant dual antiplatelet therapy. Target temperature management, including mild therapeutic hypothermia (MTH), should be applied in comatose patients after resuscitation. However, an increased risk of stent thrombosis in patients undergoing hypothermia is observed. The aim of this study was to assess the impact of MTH on pharmacokinetics of ticagrelor in cardiac arrest survivors with MI treated with MTH and PCI.. In a prospective, observational, single-center study pharmacokinetics of ticagrelor were evaluated in 41 MI patients, including 11 patients after OHCA undergoing MTH (MTH group) and 30 MI patients without OHCA and MTH (no-MTH group). Blood samples were drawn before administration of a 180 mg ticagrelor loading dose, and 30 min, 1, 2, 4, 6, 12, and 24 h after the loading dose.. In patients treated with MTH total exposure to ticagrelor during the first 12 h after the loading dose and maximal plasma concentration of ticagrelor were significantly lower than in the no-MTH group (AUC(0-12): 3403 ± 2879 vs. 8746 ± 5596 ng·h/mL, difference: 61%, p = 0.01; Cmax: 475 ± 353 vs. 1568 ± 784 ng/mL, p = 0.0002). Time to achieve maximal ticagrelor plasma concentration was also delayed in the MTH group (tmax for ticagrelor: 12 [6-24] vs. 4 [2-12] h, p = 0.01).. Bioavailability of ticagrelor was substantially decreased and delayed in MI patients treated with MTH after OHCA.. ClinicalTrials.gov Identifier: NCT02611934.

Topics: Biological Availability; Humans; Hypothermia, Induced; Myocardial Infarction; Out-of-Hospital Cardiac Arrest; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Ticagrelor; Treatment Outcome

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

See Article Schmucker et al.

Topics: Aged; Clopidogrel; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor

The recent publication of the PEGASUS and COMPASS studies could have a great influence on the clinical management of patients with stable ischemic heart disease. In the presence of possible eligibility for both approaches, a practical tool based on inclusion/exclusion criteria of the two studies could be useful for clinical decision of ideal treatment for suitable patients. We therefore report a simple nomogram helpful in identifying the treatment indicated on the base of patient's characteristics.

Topics: Aspirin; Cerebrovascular Disorders; Clinical Decision-Making; Clinical Protocols; Drug Administration Schedule; Drug Therapy, Combination; Factor Xa Inhibitors; Humans; Myocardial Infarction; Myocardial Ischemia; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Registries; Risk; Rivaroxaban; Ticagrelor

We assessed the effects of ticagrelor, aspirin and prasugrel, started 7days after myocardial ischemia-reperfusion injury on remodeling, inflammation and fibrosis in the rat. We examined whether ticagrelor can affect the number of progenitor cells in the border zone. Ticagrelor, started 24h after myocardial ischemia-reperfusion injury, attenuates the decrease in heart function and adverse remodeling, an effect which is blocked by aspirin.. Rats underwent 40min ischemia followed by reperfusion. Oral dosing with vehicle, ticagrelor (300mg/kg/d), aspirin (20mg/kg/d), their combination or prasugrel (15mg/kg/d) started 7days after infarction. Echocardiography was used to assess systolic function. Heart tissue were analyzed by rt-PCR, immunoblotting, ELISA and immunohistochemistry 2weeks after infarction.. Both ticagrelor and aspirin attenuated the decrease in systolic function and remodeling, an effect that was blocked by their combination. Ticagrelor and aspirin attenuated the increase in ANP, BNP, collagen-I and collagen-III. Again, the effect was blocked by their combination. Ticagrelor increased c-Kit, Sca-1, Ki-67, CD34, attenuated the decrease in CD105 mRNA levels, and attenuated the increase in CD31, whereas aspirin increased Ki-67, suppressed the increase in CD31 and attenuated the decrease in CD105 mRNA levels. Prasugrel did not display any effects.. Ticagrelor attenuated adverse remodeling and deterioration of left ventricular systolic function despite starting treatment after the myocardial ischemia-reperfusion injury is completed. Aspirin had similar effects; however, when combined with ticagrelor, the protective effects were significantly attenuated. Ticagrelor increased the levels of several markers of stem cells and regeneration, suggesting cardiac healing by recruiting regenerative cells into the infarct.

Topics: Animals; Apoptosis; Aspirin; Atrial Natriuretic Factor; Disease Models, Animal; Drug Therapy, Combination; Endoglin; Fibrosis; Gene Expression Regulation; Myocardial Infarction; Myocardial Reperfusion Injury; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proto-Oncogene Proteins c-kit; Rats; Rats, Sprague-Dawley; Stem Cells; Ticagrelor; Ventricular Function, Left; Ventricular Remodeling

Clinical outcomes in acute coronary syndrome patients treated with P2Y. We examined clinical outcomes in acute coronary syndrome patients in relation to the timing of CABG following P2Y. Among 508 patients (95 ticagrelor, 413 clopidogrel), the timing of CABG following P2Y. CABG within 72 h after P2Y

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Case-Control Studies; Clopidogrel; Coronary Angiography; Coronary Artery Bypass; Female; Humans; Ischemia; Male; Middle Aged; Myocardial Infarction; Postoperative Hemorrhage; Prospective Studies; Purinergic P2Y Receptor Antagonists; Stroke; Ticagrelor; Time Factors; Treatment Outcome; Withholding Treatment

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

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

To characterize ticagrelor exposure-response relationship for platelet inhibition in patients with stable coronary artery disease (CAD) and a history of myocardial infarction (MI), using nonlinear mixed effects modelling and simulation.. Platelet function data were integrated with plasma concentration data of ticagrelor and its active metabolite AR-C1249010XX in a population pharmacokinetic (PK) and pharmacodynamic (PD) model, based on two clinical studies. In the ONSET/OFFSET study, PK and platelet function were assessed in 123 CAD patients receiving placebo, ticagrelor (180 mg followed by 90 mg twice daily) or clopidogrel (600 mg followed by 75 mg once daily). In the PEGASUS-TIMI 54 platelet function substudy, PK and platelet function were assessed during maintenance dosing in 180 prior MI patients receiving placebo, ticagrelor 60 mg or ticagrelor 90 mg twice daily.. Platelet inhibition by ticagrelor was described by a sigmoidal E. In patients with stable CAD or a history of MI, near maximal platelet inhibition is achieved with both ticagrelor 60 and 90 mg twice daily. At modelled doses <60 mg, the response is reduced overall, more variable between patients, and patients will display greater peak-to-trough variability.

Topics: Adult; Aged; Aged, 80 and over; Blood Platelets; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Coronary Artery Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Models, Biological; Multicenter Studies as Topic; Myocardial Infarction; Platelet Aggregation; Platelet Function Tests; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Ticagrelor; Treatment Outcome; Young Adult

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

Topics: Adenosine; Animals; Disease Models, Animal; Equilibrative Nucleoside Transporter 1; Ischemic Preconditioning, Myocardial; Isolated Heart Preparation; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Purinergic P2Y Receptor Antagonists; Rats, Sprague-Dawley; Ticagrelor

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

To evaluate the impact of a rapid change in preferred treatment from clopidogrel to ticagrelor on the risk of ischemic stroke following acute myocardial infarction (AMI).. Data for AMI patients treated with either clopidogrel or ticagrelor were obtained from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA). Patients were divided into two cohorts, each covering a two-year time period; the initial prescription of ticagrelor (20 Dec 2011) was used as a cut-off point. Patients in the early cohort (n = 23,447) were treated with clopidogrel, while those in the later cohort (n = 24,227), were treated with either clopidogrel (47.9%) or ticagrelor (52.1%). Kaplan-Meier analyses were used to assess the risk of ischemic stroke over time, with multivariable Cox regression analyses used to identify predictors of ischemic stroke.. Of 47,674 patients, there were 1203 cases of ischemic stroke. Cumulative Kaplan-Meier incidence estimates of ischemic stroke after one year were 2.8% vs. 2.4% for the early and late cohorts, respectively (p = 0.001). Older age, hypertension, diabetes, previous stroke, congestive heart failure, atrial fibrillation, and ST-elevation myocardial infarction were associated with an increased risk of ischemic stroke. Percutaneous coronary intervention and statins at discharge were associated with a decreased risk of ischemic stroke, as was higher estimated glomerular filtration rate. Membership of the late cohort correlated with a 13% reduction in the relative risk of ischemic stroke.. The introduction of ticagrelor as well as an improved management of AMI was associated with a lower rate of ischemic stroke in a relatively unselected AMI population.

Topics: Aged; Brain Ischemia; Clopidogrel; Comorbidity; Humans; Incidence; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Registries; Risk Assessment; Risk Factors; Stroke; Sweden; Ticagrelor; Time Factors; Treatment Outcome

Topics: Blood Platelets; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor

Although the new oral P2Y12 inhibitors, prasugrel/ticagrelor have shown greater efficacy than clopidogrel in patients with the acute coronary syndrome, but they have not shown better efficacy in Korean patients. So we evaluated the efficacy of the prasugrel/ticagrelor in patients with myocardial infarction (MI) and diabetes, a more high-risk patients group.From the Korea Acute Myocardial Infarction Registry-National Institute of Health, 3985 patients with MI and diabetes who underwent PCI were enrolled between November 2011 and December 2015. The patients were divided into 2 groups: clopidogrel (n = 2985) and prasugrel/ticagrelor (n = 1000).After propensity score matching, prasugrel/ticagrelor group showed a no significant difference in risk of the composite of cardiac death (CD), recurrent MI or stroke (hazard ratio [HR], 0.705; 95% confidence interval [CI], 0.474-1.048; P = .084). However, the risk of major bleeding was significantly higher in the prasugrel/ticagrelor group. (HR; 2.114, 95% CI; [1.027-4.353], P = .042). In subgroup analysis, major bleeding was significantly increased in the subgroup of creatinine clearance <60 ml/min/1.73 m, hypertension, underwent a trans-femoral approach and diagnosed as NSTEMI among the prasugrel/ticagrelor group.The use of prasugrel/ticagrelor did not improve the composite of CD, recurrent MI or stroke, however, significantly increased major bleeding events in Korean patients with MI and diabetes undergoing PCI.

Topics: Aged; Clopidogrel; Cohort Studies; Comorbidity; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Myocardial Infarction; Outcome and Process Assessment, Health Care; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Postoperative Period; Prasugrel Hydrochloride; Republic of Korea; Thromboembolism; 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

Limited data are available concerning differences in clinical outcomes for real-life patients treated with ticagrelor versus prasugrel after percutaneous coronary intervention (PCI).. Our objective was to determine and compare the efficacy and safety of ticagrelor and prasugrel in a real-world population.. RENAMI was a retrospective, observational registry including the data and outcomes of consecutive patients with acute coronary syndrome (ACS) who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT) between January 2012 and January 2016. The mean follow-up period was 17 ± 9 months. In total, 11 university hospitals from six European countries participated. After propensity-score matching, there were no substantial differences in the baseline clinical and interventional features. All patients were treated with acetylsalicylic acid plus prasugrel 10 mg once daily or acetylsalicylic acid plus ticagrelor 90 mg twice daily. Mean duration of DAPT was 12.04 ± 3.4 months with prasugrel and 11.90 ± 4.1 months with ticagrelor (p = 0.47). The primary and secondary endpoints were long-term net adverse clinical events (NACE) and major adverse cardiovascular events (MACE), respectively, along with their single components. Subgroup analysis for freedom from NACE and MACE was performed according to length of DAPT and clinical presentation [ST-elevation myocardial infarction (STEMI)-ACS versus non-ST-elevation myocardial infarction (NSTEMI)-ACS].. In total, 4424 patients (2725 ticagrelor, 1699 prasugrel) were enrolled. After propensity-score matching, 1290 patients in each cohort were included in the analysis. At 12 months, the incidence of both NACE and MACE was lower with prasugrel (NACE: 5.3% vs. 8.5% [p = 0.001]; MACE: 5% vs. 8.1% [p =  0.001]) mainly driven by a reduction in recurrent myocardial infarction (MI) (2.4 vs. 4.0%; p = 0.029) and a lower rate of Bleeding Academic Research Consortium (BARC) 3-5 bleeding (1.5 vs. 2.9%; p = 0.011). The benefit of prasugrel was confirmed for patients with NSTEMI and for those discharged with a DAPT regimen of ≤ 12 months. Only a trend in the reduction of NACE and MACE was noted for STEMI or for those treated with longer DAPT.. Comparison of these drugs suggested that prasugrel is safer and more efficacious than ticagrelor in combination with aspirin after NSTEMI but not STEMI. No differences were found for events occurring after 12 months. The nonrandomized design of the present research means further studies are required to support these findings.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Europe; Female; Humans; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Propensity Score; Registries; Retrospective Studies; Ticagrelor; Treatment Outcome

Topics: Aspirin; Coronary Artery Bypass; Fibrinolytic Agents; Humans; Myocardial Infarction; Ticagrelor

Topics: Acute Coronary Syndrome; Aged; Drug Substitution; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Polysomnography; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Recurrence; Sleep Apnea, Central; 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

Topics: Humans; Myocardial Infarction; Percutaneous Coronary Intervention; ST Elevation Myocardial Infarction; Ticagrelor

We recently showed that ticagrelor reduced myocardial ischemia-reperfusion injury (IRI) and downregulated galectin-3 in the ischemic myocardium. This study tested the hypothesis that ticagrelor could reduce IRI through the NF-κB pathway. Rats were randomly divided into sham-operated group, placebo group (gastric administration of saline after IRI), ticagrelor group (gastric administration of ticagrelor after left anterior descending artery ligation), dextran sodium sulfate (DSS) group (DSS was added to drinking water 7 days before IRI), and DSS + ticagrelor group (DSS was added to drinking water 7 days before IRI and gastric administration of ticagrelor after left anterior descending artery ligation). Ticagrelor significantly reduced the infarct size and plasma cTnI at 3 and 7 days after IRI, significantly downregulated protein and mRNA expressions of NF-κB and galectin-3, and mRNA expressions of IL-6 and TNF-α in the ischemic area at 24 hours, 3 and 7 days after IRI. Ticagrelor also significantly decreased plasma high-sensitivity C-reactive protein and NT-proBNP levels at 24 hours and 3 days after IRI. Furthermore, pretreatment with DSS blocked the beneficial effects of ticagrelor. Our study indicates that the cardioprotective effect of ticagrelor might be partly mediated by inhibiting the NF-κB pathway in this rat model of IRI.

Topics: Animals; Anti-Inflammatory Agents; C-Reactive Protein; Disease Models, Animal; Galectin 3; Interleukin-6; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Natriuretic Peptide, Brain; NF-kappa B; Peptide Fragments; Rats, Sprague-Dawley; Signal Transduction; Ticagrelor; Troponin I; Tumor Necrosis Factor-alpha

Topics: Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Ticagrelor

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

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

Topics: Angioplasty; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor

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

Topics: Cost-Benefit Analysis; Humans; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Ticagrelor

Topics: Cost-Benefit Analysis; Humans; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Ticagrelor

The full benefits of myocardial revascularization strategies applied to acute myocardial infarction patients might be reduced by myocardial ischaemia and reperfusion (I/R) injury. It is known that inflammation plays an important role in the pathogenesis of I/R injury and galectin-3, a known inflammatory factor, is actively involved in ischaemia-induced inflammation and fibrosis of various organs. Previous studies demonstrated that anti-platelets therapy with ticagrelor, a new P2Y12 receptor antagonist, could effectively attenuate myocardial I/R injury and I/R injury-related inflammatory responses. It remains unknown whether the cardioprotective effects of ticagrelor are also mediated by modulating myocardial galectin-3 expression.. Our results showed that ticagrelor treatment significantly reduced IA/AAR ratio at 3 and 7 days post I/R, downregulated mRNA and protein expression of galectin-3, as well as mRNA expression of TNF-α and IL-6 in infarct area at 24 h, 3 and 7 days post I/R.. Our results suggest that the cardioprotective effects of ticagrelor might partly be mediated by downregulating galectin-3 expression in infarct area in this rat model of myocardial I/R injury.

Topics: Animals; Anti-Inflammatory Agents; Cytoprotection; Disease Models, Animal; Down-Regulation; Galectin 3; Inflammation Mediators; Interleukin-6; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; Rats, Sprague-Dawley; Ticagrelor; Time Factors; Tumor Necrosis Factor-alpha

Topics: Acute Coronary Syndrome; Angioplasty; Humans; Myocardial Infarction; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor

Topics: Aged; Cheyne-Stokes Respiration; Clopidogrel; Dyspnea; Humans; Male; Myocardial Infarction; Polysomnography; Ticagrelor

Third-generation P2Y

Topics: Aged; Asia; Aspirin; Clopidogrel; Drug Administration Schedule; Female; Humans; Incidence; Inpatients; Male; Middle Aged; Myocardial Infarction; Outcome Assessment, Health Care; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Propensity Score; Proportional Hazards Models; Prospective Studies; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Registries; Republic of Korea; Stroke; Ticagrelor; Treatment Outcome

To compare ticagrelor and prasugrel with clopidogrel for recurrent fatal and non-fatal myocardial infarction (reMI) in real-life conditions.. Case-referent study using the Pharmacoepidemiological General Research eXtension (PGRx)-acute coronary syndrome (ACS) registry. Cases were patients with reMI from a cohort with index ACS or external to the cohort (same sites). Referents from the cohort, without recurrent event, were matched on index ACS type and date, age and sex with reMI cases. Multivariate conditional logistic regression assessed the OR (95% CI) for reMI associated with ticagrelor and prasugrel vs clopidogrel, adjusted for aspirin use and cardiovascular risk factors.. 1047 cases and 2234 matched referents were included. Compared with clopidogrel, ticagrelor and prasugrel were associated with respective ORs of 0.65 (95% CI 0.52 to 0.81) and 0.71 (95% CI 0.53 to 0.96) for reMI occurrence. ORs for ticagrelor and prasugrel vs clopidogrel were: 0.50 (95% CI 0.38 to 0.67) and 0.66 (95% CI 0.45 to 0.95), 0.39 (95% CI 0.24 to 0.62) and 0.44 (95% CI 0.26 to 0.75), 0.63 (95% CI 0.43 to 0.92) and 1.20 (95% CI 0.69 to 2.07), 1.11 (95% CI 0.72 to 1.72) and 0.82 (95% CI 0.44 to 1.54) when index ACS was a first MI, a first ST-elevated MI (STEMI), a first non-STEMI and a recurrent ACS, respectively, and 0.63 (95% CI 0.45 to 0.87) and 0.77 (95% CI 0.41 to 1.45) for patients aged ≥70  years.. This real-world study showed a significant reduction of reMI with new antiplatelets compared with clopidogrel, ticagrelor being associated with a greater decrease of risk notably for first, either STEMI or non-STEMI. The larger magnitude of effect may be attributed to potential residual confounding or higher effectiveness compared with efficacy reported in trials (EMA Post Authorisation Study Registry Number EUPAS5905).

Topics: Age Factors; Aged; Aspirin; Case-Control Studies; Clopidogrel; Drug Therapy, Combination; Female; France; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Recurrence; Registries; Risk Factors; Secondary Prevention; Sex Factors; Ticagrelor

Topics: Acute Coronary Syndrome; Clopidogrel; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Ticagrelor

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

There is little information regarding comparison of ticagrelor and prasugrel in patients with ST-segment elevation myocardial infarction (STEMI). We sought to compare clinical outcomes between ticagrelor and prasugrel in STEMI.Methods and Results:A total of 1,440 patients with STEMI who underwent successful primary percutaneous coronary intervention were analyzed; the data were obtained from the Korea Acute Myocardial Infarction Registry-National Institutes of Health. Of the patients, 963 received ticagrelor, and 477 received prasugrel. The primary study endpoint was 12-month major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), and target vessel revascularization (TVR). MACE occurred in 91 patients (6.3%) over the 1-year follow-up, and there were no differences in the incidence of MACE (hazard ratio [HR] 1.20, 95% confidence interval [CI] 0.76-1.91, P=0.438) between the 2 groups. Analysis by propensity score matching (429 pairs) did not significantly affect the results. The incidence of in-hospital major bleeding events was still comparable between the 2 groups (2.4% vs. 2.5%, odds ratio 0.75, 95% CI 0.30-1.86, P=0.532), and there was no significant difference in the incidence of MACE (5.4% vs. 5.8%, HR 0.98, 95% CI 0.56-1.74, P=0.951) after matching.. Ticagrelor and prasugrel showed similar efficacy and safety profiles for treating STEMI in this Korean multicenter registry.

Topics: Aged; Cardiovascular Diseases; Cohort Studies; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Registries; Republic of Korea; ST Elevation Myocardial Infarction; Ticagrelor; 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

Topics: Coronary Artery Disease; Humans; Myocardial Infarction; Secondary Prevention; Ticagrelor

Topics: Acute Coronary Syndrome; Angioplasty; Humans; Myocardial Infarction; Prasugrel Hydrochloride; Ticagrelor

Topics: Acute Coronary Syndrome; Angioplasty; Humans; Myocardial Infarction; Prasugrel Hydrochloride; Ticagrelor

Ticagrelor is a P2Y. Our contemporary analysis shows a modest but significant increase in the use of ticagrelor and a high rate of adherence to the use of low-dose aspirin at discharge.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Drug Prescriptions; Drug Therapy, Combination; Female; Guideline Adherence; Humans; Male; Middle Aged; Myocardial Infarction; Patient Discharge; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Practice Patterns, Physicians'; Purinergic P2Y Receptor Antagonists; Registries; Ticagrelor; Treatment Outcome; United States

Topics: Aged; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Time Factors; Withholding Treatment

Aims It is unknown whether dual antiplatelet therapy with ticagrelor instead of clopidogrel reduces the risk of ischaemic stroke in acute myocardial infarction patients that undergo percutaneous coronary intervention. This study investigated whether the introduction of dual antiplatelet therapy with ticagrelor was associated with reduced ischaemic stroke risk in a real-world population. Methods and results Patients with ischaemic stroke after acute myocardial infarction from 8 December 2009-31 December 2013 were identified using the Register for Information and Knowledge on Swedish Heart Intensive Care Admissions and the Swedish National Patient Register. The study period was divided into two similar periods using the date of the first prescription of ticagrelor as the cut-off. The risk of ischaemic stroke in percutaneous coronary intervention-treated acute myocardial infarction patients during the first period (100% clopidogrel treatment) versus the second period (60.7% ticagrelor treatment) was assessed using Kaplan-Meier analysis. Variables associated with ischaemic stroke were identified using a multivariable Cox proportional hazards model. There were 686 ischaemic stroke events (2.0%) among 34931 percutaneous coronary intervention-treated acute myocardial infarction patients within one year, 366 (2.2%) during the first period and 320 (1.8%) during the second period ( p = 0.004). The Cox model showed a 21% relative risk reduction in ischaemic stroke in the second period versus the first one (hazard ratio 0.79, 95% confidence interval, 0.68-0.92; p = 0.003). The independent predictors of increased stroke risk were older age, hypertension, diabetes mellitus, atrial fibrillation, heart failure during hospitalization, previous ischaemic stroke, and ST-segment elevation myocardial infarction. Conclusion The risk of ischaemic stroke in percutaneous coronary intervention-treated acute myocardial infarction patients decreased after the introduction of ticagrelor in Sweden.

Topics: Aged; Brain Ischemia; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Incidence; Male; Myocardial Infarction; Percutaneous Coronary Intervention; Prognosis; Purinergic P2Y Receptor Antagonists; Registries; Retrospective Studies; Sweden; Ticagrelor; Time Factors

Acute ST-segment elevation of myocardial infarction (STEMI) is the most severe type of acute coronary syndrome (ACS). Particular attention has been focused on studying the pathogenesis of STEMI, and how to prevent thrombosis, reduce inflammatory reaction, stabilize plaques and improve vascular endothelial functions to preserve the survived myocardium. This study aimed to compare the anti-inflammatory endothelium-protective effects, clinical prognosis, and relevant bleeding risks of ticagrelor versus clopidogrel in patients with STEMI who underwent urgent percutaneous coronary intervention (PCI) and provide certain experimental evidence and a theoretical basis for the selection of safe and effective drugs and their proper dosage, thereby further guiding clinical medication.. We sequentially enrolled 193 patients (104 males and 89 females) admitted to hospital due to acute STEMI. These patients underwent urgent PCI between December 2013 and May 2015 and met the inclusion criteria. They were assigned (1: 1) into two groups according to different treatments, 97 patients in the ticagrelor group (treatment group), and 96 patients in the clopidogrel group (control group). Levels of hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), and endothelial cell-specific molecule 1 (ESM-1) taken at admission and 24 h, 4 days, and 7 days after administration, as well as the correlation between the levels of IL-6, hs-CRP, and ESM-1, were determined in the two groups. At the same time, the effects of treatment with ticagrelor and clopidogrel on the efficacy endpoint events (ischemic and safety) were explored.. No statistically significant difference was found in the levels of hs-CRP, IL-6, or ESM-1 at admission between the two groups (P> 0.05); Their levels were significantly elevated 24 h after administration, with statistical differences between two groups (P< 0.05). Furthermore, a downward trend with statistically significant differences was found on Day 4 and Day 7 (P< 0.05); ESM-1 levels increased along with increases of hs-CRP and IL-6 levels, indicating ESM-1 was positively correlated with hs-CRP (r=0.523, P< 0.001) and IL-6 (r=0.431, P< 0.001); and the occurrence rates of ischemic endpoint events at 30 days were lower in the treatment group than in the control group. The occurrence of safety endpoint events was higher than in the control group; however, no statistically significant difference was found (P> 0.05).. Compared with clopidogrel, ticagrelor appears to rapidly reduce the prevalence of inflammatory reactions and stabilize the functions of vascular endothelium to improve the stability of atherosclerotic plaque and decrease the occurrence rate of thrombosis as well as ischemic outcome events without any obvious increase in the risk of bleeding in patients with acute STEMI receiving urgent PCI. This renders it a potential drug for clinical practice. At the same time, measurement of ESM-1, a new biological marker for vascular endothelial function disorder, could possibly become a simple, effective, and practical new method for clinical evaluation of risk stratification of patients with acute STEMI at admission.

Topics: Adenosine; Adult; Aged; Biomarkers; C-Reactive Protein; Clopidogrel; Endothelium, Vascular; Female; Humans; Interleukin-6; Male; Middle Aged; Myocardial Infarction; Neoplasm Proteins; Percutaneous Coronary Intervention; Pilot Projects; Platelet Aggregation Inhibitors; Prognosis; Proteoglycans; Ticagrelor; Ticlopidine; Treatment Outcome

P2Y12 antagonists are the standard in antiplatelet therapy but their potential effects on functional myocardial recovery and cardioprotection post-myocardial infarction (MI) are unknown. We investigated in a preclinical model of MI whether ticagrelor and clopidogrel differently affect cardiac repair post-MI.. Pigs either received: (i) clopidogrel (600 mg; 75 mg/qd); (ii) ticagrelor (180 mg; 90 mg/bid); and (iii) placebo control. MI was induced by mid-left anterior descending coronary artery balloon occlusion (60 min) and animals received the maintenance doses for the following 42 days. Serial cardiac magnetic resonance was performed at Day 3 and Day 42 for the assessment of global and regional cardiac parameters. We determined cardiac AMP-activated protein kinase (AMPK), Akt/PKB, aquaporin-4, vascular density, and fibrosis. In comparison to controls, both P2Y12 antagonists limited infarct expansion at Day 3, although ticagrelor induced a further 5% reduction (P < 0.05 vs. clopidogrel) whereas oedema was only reduced by ticagrelor (≈23% P < 0.05). Scar size decreased at Day 42 in ticagrelor-treated pigs vs. controls but not in clopidogrel-treated pigs. Left ventricular ejection fraction was higher 3 days post-MI in ticagrelor-treated pigs and persisted up to Day 42 (P < 0.05 vs. post-MI). Regional analysis revealed that control and clopidogrel-treated pigs had severe and extensive wall motion abnormalities in the jeopardized myocardium and a reduced myocardial viability that was not as evident in ticagrelor-treated pigs (χ2P < 0.05 vs. ticagrelor). Only ticagrelor enhanced myocardial AMPK and Akt/PKB activation and reduced aquaporin-4 levels (P < 0.05 vs. control and clopidogrel). No differences were observed in vessel density and fibrosis markers among groups.. Ticagrelor is more efficient than clopidogrel in attenuating myocardial structural and functional alterations post-MI and in improving cardiac healing. These benefits are associated with persistent AMPK and Akt/PKB activation.

Topics: AMP-Activated Protein Kinases; Animals; Clopidogrel; Disease Models, Animal; Echocardiography; Fibrosis; Heart Ventricles; Magnetic Resonance Imaging, Cine; Myocardial Infarction; Myocytes, Cardiac; Proto-Oncogene Proteins c-akt; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2; Receptors, Purinergic P2Y12; Signal Transduction; Stroke Volume; Sus scrofa; Ticagrelor; Time Factors; Ventricular Function, Left; Ventricular Remodeling

Inflammatory bowel diseases have been recognized as predisposing factors to atherosclerosis and thrombotic events, involving both the venous and the arterial circulatory systems. We report the case of a 70-year-old man who presented with ST elevation myocardial infarction during the active phase of ulcerative colitis (UC). Because of the ongoing hematochezia, after successful revascularization of the culprit vessel, the patient was medicated with Clopidogrel, in place of one of the more powerful new oral P2Y

Topics: Abciximab; Aged; Angioplasty, Balloon, Coronary; Clopidogrel; Colitis, Ulcerative; Coronary Thrombosis; Humans; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Complications; Stents; Ticagrelor

Topics: Animals; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Swine; Ticagrelor

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

Topics: Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Prognosis; Stroke; Ticagrelor

Background and Purpose- Guidelines recommend dual antiplatelet treatment with ticagrelor instead of clopidogrel after acute myocardial infarction. Ticagrelor increases major and minor noncoronary artery bypass graft bleeding compared with clopidogrel, but whether the risk of intracranial hemorrhage (ICH) increases is unknown. We aimed to examine any association between ticagrelor and ICH and to identify predictors of ICH among unselected patients after acute myocardial infarction. Methods- Patients with acute myocardial infarction were identified using the Register of Information and Knowledge About Swedish Heart Intensive Care Admissions, and the data were combined with the Swedish National Patient Registry to identify ICH occurrence. To avoid obvious selection bias related to the choice of dual antiplatelet treatment, we divided the study cohorts into 2 time periods of similar length using the first prescription of ticagrelor as a cutoff point (December 20, 2011). The risk of ICH during the first period (100% clopidogrel treatment) versus the second period (52.1% ticagrelor and 47.8% clopidogrel treatment) was assessed using Kaplan-Meier analysis. Cox proportional-hazards regression analyses, with assessment of interactions between all significant variables, were used to identify predictors of ICH. Results- The analysis included 47 674 patients with acute myocardial infarction. The cumulative incidence of ICH during the first period was 0.59% (91 cases [95% CI, 0.49-0.69]) versus 0.52% (97 cases [95% CI, 0.43-0.61]) during the second period ( P=0.83). In multivariable Cox analysis, study period (second versus first period) was not predictive of ICH. Interaction analyses showed that age and prior cardiovascular morbidities were of importance in predicting the risk of ICH. Conclusions- The increased use of ticagrelor was not associated with ICH, whereas age and prior cardiovascular morbidities were related to the risk of ICH and interacted significantly.

Topics: Age Factors; Aged; Clopidogrel; Cohort Studies; Female; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Proportional Hazards Models; Secondary Prevention; Sweden; Ticagrelor

See Editorial by Bonaca et al.

Topics: Adenosine; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor

The effect of polyvascular disease on cardiovascular outcomes in the background of peripheral artery disease (PAD) is unclear.. To determine the risk of ischemic events (both cardiac and limb) among patients with PAD and polyvascular disease.. In this post hoc secondary analysis of the international Examining Use of Ticagrelor in Peripheral Artery Disease (EUCLID) trial, outcomes were compared among 13 885 enrolled patients with PAD alone, PAD + coronary artery disease (CAD), PAD + cerebrovascular disease (CVD), and PAD + CAD + CVD. Adjusted Cox proportional hazards regression models were implemented to determine the risk associated with polyvascular disease and outcomes, and intention-to-treat analysis was performed. The EUCLID trial was conducted from December 31, 2012, to March 7, 2014; the present post hoc analysis was performed from June 1, 2017, to February 5, 2018.. EUCLID evaluated ticagrelor vs clopidogrel in preventing major adverse cardiac events (cardiovascular death, myocardial infarction [MI], or ischemic stroke) and major bleeding in patients with PAD.. The primary end point was a composite of cardiovascular death, MI, or ischemic stroke. Key secondary end points included the individual components of the primary end point and acute limb ischemia leading to hospitalization, major amputation, and lower-extremity revascularization. The primary end point of Thrombolysis in Myocardial Infarction (TIMI) major bleeding was also evaluated.. The EUCLID trial randomized 13 885 patients with a median age of 66 years (interquartile range, 60-73 years), of whom 3888 (28.0%) were women. At baseline, 7804 patients (56.2%) had PAD alone; 2639 (19.0%) had PAD + CAD; 2049 (14.8%) had PAD + CVD; and 1393 (10.0%) had PAD + CAD + CVD. Compared with patients with isolated PAD, the adjusted hazard ratios (aHRs) for major adverse cardiac events were 1.34 (95% CI, 1.15-1.57; P < .001) for PAD + CVD, 1.65 (95% CI, 1.43-1.91; P < .001) for PAD + CAD, and 1.99 (95% CI, 1.69-2.34; P < .001) for PAD + CAD + CVD. The aHRs for lower-extremity revascularization were 1.17 (95% CI, 1.03-1.34; P = .01) for PAD + CAD, 1.17 (95% CI, 1.02-1.35; P = .02) for PAD + CVD, and 1.34 (95% CI, 1.15-1.57; P < .001) for PAD + CAD + CVD. Polyvascular disease was not associated with an increased risk of acute limb ischemia (aHR for PAD + CVD, 0.91; 95% CI, 0.62-1.34, P = .63; PAD + CAD, 0.93; 95% CI, 0.64-1.34, P = .69; and PAD + CAD + CVD, 0.98; 95% CI, 0.63-1.53, P = .93), major amputation (aHR for PAD + CVD, 0.83; 95% CI, 0.54-1.27, P = .40; PAD + CAD, 0.74; 95% CI, 0.47-1.16, P = .19; and PAD + CAD + CVD, 1.12; 95% CI, 0.69-1.80, P = .65), or TIMI major bleeding (PAD + CVD, 0.98; 0.66-1.44, P = .91; PAD + CAD, 1.04; 0.74-1.48, P = .81; and PAD + CAD + CVD, 0.96; 95% CI, 0.62-1.51, P = .88).. Compared with patients with PAD alone, the risk of major adverse cardiac events and lower-extremity revascularization increased with multiple vascular bed involvement. There was no clear increased risk of bleeding associated with polyvascular disease.

Topics: Aged; Female; Humans; Male; Middle Aged; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Ticagrelor

Topics: Heart; Humans; Myocardial Infarction; Prasugrel Hydrochloride; Ticagrelor

Topics: Heart; Humans; Myocardial Infarction; Prasugrel Hydrochloride; Ticagrelor

Topics: Acute Coronary Syndrome; Adenosine; Humans; Myocardial Infarction; Patient Discharge; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Ticlopidine

Topics: Clopidogrel; Dose-Response Relationship, Drug; Humans; Magnetic Resonance Imaging, Cine; Myocardial Infarction; Myocardium; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Preoperative Period; Severity of Illness Index; Ticagrelor

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

Topics: Aspirin; Belgium; Clopidogrel; Diabetes Mellitus; Drug Therapy, Combination; Humans; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Stroke; Ticagrelor; Treatment Outcome

Although Asian people are believed to be more susceptible to bleeding on currently recommended dose of ticagrelor, there is limited evidence supporting low-dose ticagrelor. We prospectively randomized patients receiving dual antiplatelet therapy with aspirin and clopidogrel into 3 groups; aspirin plus clopidogrel 75 mg versus aspirin plus ticagrelor 90 mg once daily versus aspirin plus ticagrelor 45 mg twice daily. Platelet function assessments were conducted using VerifyNow P2Y12 assay at baseline and 28 days after randomization. No differences in baseline P2Y12 reaction unit (PRU) values were observed among the 3 groups. PRU values at the end of the treatment periods were significantly lower in low-dose ticagrelor (90 mg QD group, 98.6 ± 73.4 and 45 mg BID group, 65.5 ± 58.8) compared with clopidogrel (221.2 ± 50.1, both p <0.001). There was no significant difference in PRU values between 2 groups of low-dose ticagrelor (p = 0.208). The rates of high on-treatment platelet reactivity were significantly lower in low-dose ticagrelor compared with clopidogrel, whereas clopidogrel showed higher rate of optimal on-treatment platelet reactivity than ticagrelor 45 mg BID. However, similar rate of optimal on-treatment platelet reactivity was observed in clopidogrel and ticagrelor 90 mg QD. In conclusion, low-dose ticagrelor treatment, either with 90 mg QD or 45 mg BID, was associated with a more potent antiplatelet effect compared with clopidogrel treatment and once daily dose provided similar antiplatelet effect but favorable effect on optimal platelet inhibition compared with twice daily dose.

Topics: Adenosine; Aged; Clopidogrel; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Postoperative Care; Prospective Studies; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Topics: Cost-Benefit Analysis; Humans; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Ticagrelor

Patients with acute myocardial infarction pretreated with prasugrel or ticagrelor may require urgent coronary artery bypass grafting (CABG). However, prasugrel and ticagrelor withdrawal period is recommended for 5-7 days before planned CABG to enable full platelet recovery. We hypothesized that monitoring sequential platelet reactivity (PR) could identify patients with early platelet recovery who may benefit from earlier surgery before the guideline-recommended 5-7 day delay.. We performed preoperative PR assays in 35 patients with acute myocardial infarction who received prasugrel (60%) or ticagrelor (40%) and required an urgent CABG. When platelet inhibition levels were favorable, on the basis of the VerifyNow assay, surgery was endorsed. CABG-related bleeding parameters were collected and compared with two matched control groups composed of patients who received fewer potent antiplatelet regimens.. On the basis of platelet function monitoring, we identified 21 (56.7%) patients with a relatively earlier platelet recovery who underwent CABG before the end of the conventional washout period (5-7 days). For these patients, the washout periods were shortened to an average time of 2.6±1.0 days for ticagrelor and 3.8±1.5 days for prasugrel. CABG-related bleeding parameters were comparable with the two matched control groups.. A strategy of performing preoperative PR assays can identify patients who recover platelet function in less than 5-7 days after ticagrelor or prasugrel discontinuation. This strategy may provide the basis for performing urgent CABGs earlier than the currently recommended delay. Future, larger studies are required to establish these preliminary findings.

Topics: Adenosine; Aged; Blood Loss, Surgical; Coronary Artery Bypass; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Myocardial Infarction; Pilot Projects; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Point-of-Care Testing; Postoperative Hemorrhage; Prasugrel Hydrochloride; Predictive Value of Tests; Preoperative Period; Risk Factors; Ticagrelor; Time Factors; Time-to-Treatment; Treatment Outcome

BACKGROUND Clopidogrel is commonly used in the prevention and treatment of cardiovascular events. However, despite clopidogrel treatment, some patients experience recurrent ischemic events. CASE REPORT We present the case of a 58-year-old man with polycythemia vera and concomitant thrombocytosis who suffered 6 episodes of cerebral infarctions and 1 myocardial infarction, despite treatment with clopidogrel. Following his last ischemic event, the antiplatelet therapy was intensified from initially clopidogrel monotherapy to dual antiplatelet therapy with aspirin 75 mg once daily and ticagrelor 90 mg twice daily. Since then, no cardiovascular event has been reported. CONCLUSIONS This case report illustrates that insufficient platelet inhibition with clopidogrel monotherapy in a patient with thrombocytosis may be associated with recurrent arterial thrombosis. The exact reasons for the insufficient platelet inhibition are not known, but a plausible explanation may be an accelerated platelet turnover reflected by an increased number of immature platelets in this patient.

Topics: Adenosine; Brain Infarction; Clopidogrel; Drug Therapy, Combination; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Polycythemia Vera; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Thrombocytosis; Ticagrelor; Ticlopidine

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

Topics: Adenosine; Aspirin; China; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Thrombolytic Therapy; Ticagrelor; Ticlopidine; Treatment Outcome

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

After myocardial infarction (MI) treated with percutaneous coronary intervention (PCI), guidelines recommend dual antiplatelet therapy (DAPT) with aspirin and an ADP receptor inhibitor (ADPri) for at least 1year. However, whether real-world Canadian practice patterns reflect this recommendation is unknown.. We studied 2175 MI patients treated with PCI and discharged from 26 Canadian hospitals between 12/2011 and 05/2013 in the Canadian Observational Antiplatelet sTudy (COAPT). Hierarchical Cox proportional hazard regression modeling was used to determine baseline demographic and clinical factors associated with duration of ADPri therapy post-discharge.. At index-hospitalization discharge, 1597 (73%) patients were treated with clopidogrel, 220 (10%) with prasugrel, and 358 (17%) with ticagrelor. ADPri was discontinued prior to 1year in 474 (21.8%) patients; discontinuation rates were lowest for patients discharged on prasugrel (17.7%), compared with clopidogrel (22.5%) or ticagrelor (21.0%), (log rank test, p=0.03). In addition to regional variability, factors associated with shorter ADPri duration included older age, low body weight, Killip III/IV heart failure, atrial fibrillation, ticagrelor on discharge, and bare metal stent use, while longer ADPri duration was associated with history of prior MI.. One in five PCI-treated MI patients did not complete Canadian guideline-recommended 1-year course of ADPri treatment. Premature ADPri discontinuation was most strongly associated with factors that increase the risk of bleeding. Further study is required to assess the clinical implications of premature ADPri discontinuation on patient outcomes.

Topics: Adenosine; Aged; Canada; Clopidogrel; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Retrospective Studies; Ticagrelor; Ticlopidine; Treatment Outcome

Patients pretreated with ticagrelor with less than 1 hour from percutaneous coronary intervention (PCI) or receiving ticagrelor in cath lab were prospectively included and received cangrelor. Cangrelor was infused for 2 hours and platelet function was assessed as P2Y12 reactivity units (PRU) with the VerifyNow P2Y12 function assay before start of infusion, 15 min after the start of infusion, and 30 min after the end of infusion. A total of n = 32 patients with an average age of 68 (±13) years with n = 22 (69%) males were included. The level of P2Y12 inhibition before cangrelor infusion was started was 249 PRU (IQR 221-271). After 15 min of cangrelor infusion the P2Y12 reactivity was markedly decreased to 71 PRU (IQR 52-104, p < 0.001). At 30 min after end of infusion PRU remained within the therapeutic range, 89 PRU (IQR 50-178; p < 0.001 for comparison with preinfusion) with only n = 4 (12.5%) patients with PRU >225. Results were consistent between patients receiving ticagrelor prehospital or in the cath lab and no statistical differences in PRU were noted between the two groups in any of the three measurements. In conclusion, cangrelor in combination with ticagrelor results in consistent and strong P2Y12 inhibition during and after infusion and cangrelor may bridge the gap until oral P2Y12 inhibitors achieve effect in real-world STEMI patients undergoing primary PCI.

Topics: Adenosine; Adenosine Monophosphate; Female; Humans; Male; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; 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

To examine whether a loading dose of ticagrelor on top of clopidogrel reduced postpercutaneous coronary intervention (PCI) myonecrosis.. Seventy seven coronary artery disease patients received a loading dose of 300 mg clopidogrel pre-PCI and were divided into three groups: group TT (n = 36): a loading dose of 180 mg ticagrelor pre-PCI, followed by ticagrelor 90 mg twice daily commencing one day post-PCI; group CT (n = 26): a maintenance dose of ticagrelor 90 mg twice daily; group CC (n = 15): clopidogrel 75 mg daily post- PCI. High sensitivity cardiac troponin T (hs-cTnT) and creatine kinase-MB (CK-MB) were measured pre-PCI and 0 h, 2 h or 24 h post-PCI. Platelet aggregation was measured in a separate cohort of 54 coronary artery disease patients (35 diabetic and 19 non-diabetic patients).. There were no significant differences in hs-cTnT and CK-MB concentration among the three groups. In group TT, diabetic patients had significant higher Δhs-cTnT2h-0h than non-diabetic patients. In the second cohort, although baseline platelet aggregation was higher in diabetic than non-diabetic patients, platelet aggregation was comparable between diabetic and non-diabetic patients at 0 and 2 h post-PCI.. This study indicates that a loading dose of ticagrelor does not significantly reduce post- PCI myonecrosis. Diabetes is associated with more post-PCI myonecrosis. A loading dose of ticagrelor effectively reduces platelet aggregation in diabetic patients.

Topics: Adenosine; Coronary Angiography; Dose-Response Relationship, Drug; Elective Surgical Procedures; Electrocardiography; Female; Follow-Up Studies; Humans; Injections, Intravenous; Male; Myocardial Infarction; Percutaneous Coronary Intervention; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Ticagrelor

Topics: Adult; Chest Pain; Coronary Angiography; Diagnosis, Differential; Drug-Eluting Stents; Humans; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Purpura, Thrombotic Thrombocytopenic; Ticagrelor

Patients in a coma after cardiac arrest may have adversely affected drug absorption and metabolism. This study, the first of its kind, aimed to investigate the early pharmacokinetic and pharmacodynamic effects of ticagrelor administered through a nasogastric tube (NGT) to patients resuscitated after an out of hospital cardiac arrest (OHCA) and undergoing primary percutaneous coronary intervention (pPCI).. Blood samples were drawn at baseline and at two, four, six, eight, 12, and 24 hours and then daily for up to five days after administration of a 180 mg ticagrelor loading dose (LD), followed by 90 mg twice daily in 44 patients. The primary endpoint was the occurrence of high platelet reactivity (HPR) 12 hours after the LD. Assessment by VerifyNow (VFN) showed 96 (15.25-140.5) platelet reactivity units (PRU), and five (12%) patients exhibited HPR. Multiplate analysis showed 19 (12-29) units (U) at twelve hours, and three patients (7%) had HPR. Ticagrelor and its main metabolite AR-C124910XX concentrations were 85.2 (37.2-178.5) and 18.3 (6.4-52.4) ng/mL. Median times to sufficient platelet inhibition below the HPR limit were 3 (2-6) hours (VFN) and 4 (2-8) hours (Multiplate).. Ticagrelor, administered as crushed tablets through a nasogastric tube, leads to sufficient platelet inhibition after 12 hours, and in many cases earlier, in the vast majority of patients undergoing pPCI and subsequent intensive care management after an OHCA.

Topics: Adenosine; Blood Platelets; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Purinergic P2Y Receptor Antagonists; Ticagrelor

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

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

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Clopidogrel; Drug Therapy, Combination; Humans; Myocardial Infarction; Patient Selection; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Secondary Prevention; Ticagrelor; Ticlopidine; Time Factors

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

The study investigated dual antiplatelet therapy (DAPT) patterns over time and patient characteristics associated with the various treatments in a myocardial infarction (MI) population.. A registry-based observational cohort study was performed using antecedent data.. This study linked morbidity, mortality and medication data from Danish national registries.. All 28 449 patients admitted to a Danish hospital with a first-time MI and alive at discharge from 2009 through 2012 were included.. Primary outcome was initiation of DAPT and secondary outcomes comprised persistence in DAPT treatment and switches between DAPT treatments.. The overall proportion of patients prescribed DAPT increased from 68% (CL 95% 67-69%) to 73% (CL 95% 72-74%) from 2009 to 2012. For treatment of patients with and without percutaneous coronary intervention (PCI), the corresponding numbers were from 87% (CL 95% 86-88%) to 91% (CL 95% 90-92%) and from 49% (CL 95% 47-50%) to 52% (CL 95% 51-54%), respectively. Non-PCI patients had a higher cardiovascular risk compared with PCI patients. Among PCI patients, age>75 years, atrial fibrillation, diabetes and peripheral arterial disease were associated with a higher risk of treatment breaks for DAPT. Among patients without PCI, ticagrelor treatment was associated with an increased risk of treatment breaks during the first 12 months compared with clopidogrel treatment.. From 2009 to 2012, there was an increase in the proportion of patients with MI receiving DAPT, and a longer duration of DAPT. Still, a large proportion of patients without PCI are discharged either without DAPT or with a short DAPT duration. These findings may indicate the need for more careful attention to DAPT for patients with MI not undergoing PCI in Denmark.

Topics: Adenosine; Aged; Aged, 80 and over; Aspirin; Clopidogrel; Cohort Studies; Denmark; Drug Prescriptions; Drug Therapy, Combination; Female; Humans; Male; Medication Adherence; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Registries; Ticagrelor; Ticlopidine

 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

Topics: Adenosine; Electrocardiography; Humans; Myocardial Infarction; ST Elevation Myocardial Infarction; Ticagrelor

Ticagrelor reduces ischaemic events and mortality in acute coronary syndrome (ACS) vs. clopidogrel. We wished to study clinical outcomes in a large real-world population post-ACS.. We performed a prospective cohort study in 45 073 ACS patients enrolled into Swedish Web system for Enhancement and Development of Evidence-based care in Heart Disease Evaluated According to Recommended Therapies who were discharged on ticagrelor (N = 11 954) or clopidogrel (N = 33 119) between 1 January 2010 and 31 December 2013. The primary outcome was a composite of all-cause death, re-admission with myocardial infarction (MI) or stroke, secondary outcomes as the individual components of the primary outcome, and re-admission with bleeding. The risk of the primary outcome with ticagrelor vs. clopidogrel was 11.7 vs. 22.3% (adjusted hazard ratio (HR) 0.85 [95% confidence interval: 0.78-0.93]), risk of death 5.8 vs. 12.9% (adjusted HR 0.83 [0.75-0.92]), and risk of MI 6.1 vs. 10.8% (adjusted HR 0.89 [0.78-1.01]) at 24 months. Re-admission with bleeding with ticagrelor vs. clopidogrel occurred in 5.5 vs. 5.2% (adjusted HR 1.20 [1.04-1.40]). In a subset of patients undergoing percutaneous coronary intervention (PCI) on ticagrelor vs. clopidogrel the PCI-related in-hospital bleeding was 3.7 vs. 2.7% (adjusted odds ratio, OR, 1.57 [1.30-1.90]).. Ticagrelor vs. clopidogrel post-ACS was associated with a lower risk of death, MI, or stroke, as well as death alone. Risk of bleeding was higher with ticagrelor. These real-world outcomes are consistent with randomized trial results.

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Prospective Studies; Registries; Ticagrelor; Ticlopidine; Treatment Outcome

Topics: Adenosine; Aspirin; Drug Therapy, Combination; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Secondary Prevention; Ticagrelor; United Kingdom

Topics: Adenosine; Cheyne-Stokes Respiration; Dyspnea; Humans; Hypercapnia; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Respiratory Function Tests; Ticagrelor

The P2Y. Pigs received the following before MI induction: (1) placebo-control; (2) a loading dose of clopidogrel (600 mg); (3) a loading dose of ticagrelor (180 mg); or (4) a loading dose of ticagrelor followed by an adenosine A1/A2-receptor antagonist [8-(p-sulfophenyl)theophylline, 4 mg/kg intravenous] to determine the potential contribution of adenosine in ticagrelor-related cardioprotection. Animals received the corresponding maintenance doses of the antiplatelet agents during the following 24 hours and underwent 3T-cardiac MRI analysis. Platelet inhibition was monitored by ADP-induced platelet aggregation. In the myocardium, we assessed the expression and activation of proteins known to modulate edema formation, including aquaporin-4 and AMP-activated protein kinase and its downstream effectors CD36 and endothelial nitric oxide synthase and cyclooxygenase-2 activity.. Clopidogrel and ticagrelor exerted a high and consistent antiplatelet effect (68.2% and 62.2% of platelet inhibition, respectively, on challenge with 20 μmol/L ADP) that persisted up to 24 hours post-MI (P<0.05). All groups showed comparable myocardial area-at-risk and cardiac worsening after MI induction. 3T-Cardiac MRI analysis revealed that clopidogrel- and ticagrelor-treated animals had a significantly smaller extent of MI than placebo-control animals (15.7 g left ventricle and 12.0 g left ventricle versus 22.8 g left ventricle, respectively). Yet, ticagrelor reduced infarct size to a significantly greater extent than clopidogrel (further 23.5% reduction; P=0.0026), an effect supported by troponin-I assessment and histopathologic analysis (P=0.0021). Furthermore, in comparison with clopidogrel, ticagrelor significantly diminished myocardial edema by 24.5% (P=0.004), which correlated with infarct mass (r=0.73; P<0.001). 8-(p-Sulfophenyl)theophylline administration abolished the cardioprotective effects of ticagrelor over clopidogrel. At a molecular level, aquaporin-4 expression decreased and the expression and activation of AMP-activated protein kinase signaling and cyclooxygenase-2 increased in the ischemic myocardium of ticagrelor- versus clopidogrel-treated animals (P<0.05). These protein changes were not observed in those animals administered the adenosine receptor blocker 8-(p-sulfophenyl)theophylline.. Ticagrelor, beyond its antiplatelet efficacy, exerts cardioprotective effects by reducing necrotic injury and edema formation via adenosine-dependent mechanisms.

Topics: Adenosine; Animals; Blood Platelets; Cardiotonic Agents; Clopidogrel; Cyclooxygenase 2; Myocardial Infarction; Platelet Aggregation Inhibitors; Random Allocation; Swine; Ticagrelor; Ticlopidine

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

Drug-eluting bioresorbable vascular scaffold (BVS) is a revolutionary treatment option for obstructive coronary artery disease in percutaneous coronary intervention. It restores blood flow to the myocardium but unlike permanent metallic stent, BVS dissolves in the body within 2 years. This allows the coronary vessel to regain its normal function and motion. The clinical efficacy and safety of BVS in the first-in-human trials have been reported with low major adverse cardiac event rates observed at short- and long-term follow-up. The incidence of BVS scaffold thrombosis (ST) in these studies was 0 %. There is limited data on the incidence of BVS ST in the real world. We report 2 cases of subacute ST involving BVS in our real-world practice and discuss on the possible mechanisms of these thrombotic episodes (with insights from intracoronary imaging studies).

Topics: Absorbable Implants; Adenosine; Aged; Aspirin; Clopidogrel; Coronary Angiography; Coronary Stenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; Treatment Outcome

We describe, to the best of our knowledge, the first incidence of stent thrombosis in a patient treated with ticagrelor, who exhibited high on-treatment platelet reactivity (HTPR) according to platelet reactivity testing. He was on clopidrogel and tested for platelet reactivity using the VerifyNow P2Y12 assay. The test showed a PRU of 249 and only 12% platelet inhibition. The patient was then switched to ticagrelor, with a loading dose of 180 mg given. The patient had stent thrombosis three weeks later with an acute myocardial infarction (MI). The patient had good platelet inhibition when started on Ticagrelor treatment (PRU=33), but had HTPR when the stent thrombosis occurred three weeks later (PRU=339).

Topics: Adenosine; Aged; Angina, Stable; Coronary Artery Disease; Coronary Thrombosis; Graft Occlusion, Vascular; Humans; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Stents; Ticagrelor

High on-treatment platelet reactivity (HTPR) despite use of P2Y12 antagonists is associated with adverse cardiac events. The long-term variability in response to prasugrel and ticagrelor is unclear. Our aim was to assess residual platelet reactivity (PR) and rates of HTPR during treatment with prasugrel versus ticagrelor in patients with myocardial infarction (MI). 114 patients with MI treated with percutaneous coronary intervention (PCI) were included. Sixty-two patients were treated with prasugrel (mean age 58 ± 8 years, 21 % women, 29 % diabetes), and 52 patients with ticagrelor (mean age 63 ± 9, 19 % women, 37 % diabetes). Patients were tested for PR at 2-4 days and 30 days post-PCI, using the VerifyNow P2Y12 assay and the multiple-electrode aggregometry. Our results show a higher residual PR in patients treated with prasugrel than those treated with ticagrelor (VerifyNow: 65.4 ± 60.6 vs. 26.0 ± 24.2 P2Y12 reaction units, p < 0.001 at 2-4 days, and 67.3 ± 62.5 vs. 21.1 ± 26.1, p < 0.001 at follow-up). HTPR rates were higher in the prasugrel group (8.1-11.3 % vs. none with ticagrelor in the early test, and 8.7-10.9 % vs. none with ticagrelor at follow-up). In conclusion, in patients with MI undergoing PCI, treatment with ticagrelor resulted in greater platelet inhibition and lower HTPR rates compared with prasugrel, up to 30 days after the event.

Topics: Adenosine; Adolescent; Adult; Aged; Blood Platelets; Female; Humans; Male; Middle Aged; Myocardial Infarction; Piperazines; Platelet Activation; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Time Factors

Prasugrel and ticagrelor are potent P2Y12-ADP receptor antagonists which are superior to clopidogrel in acute coronary syndromes. To date no clinical trial directly compared these two drugs. Platelet reactivity correlates with ischemic and bleeding events in patients undergoing percutaneous coronary intervention. Recent pharmacological studies have observed a delayed onset of action of these two drugs in ST-segment elevation myocardial infarction (STEMI). We provide the first adequately powered pharmacological study comparing PR following ticagrelor and prasugrel loading dose (LD) in STEMI patients when the maximal biological effect is reached. In the present study, ticagrelor was associated with a lower rate of high on-treatment PR compared to prasugrel.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Electrocardiography; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Risk Factors; Ticagrelor; Treatment Outcome

Topics: Absorbable Implants; Adenosine; Adult; Aspirin; Blood Vessel Prosthesis; Clopidogrel; Graft Occlusion, Vascular; Humans; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Stents; Ticagrelor; Ticlopidine; Tirofiban; Tissue Scaffolds; Tyrosine

Topics: Adenosine; Clopidogrel; Coronary Thrombosis; Drug Resistance; Drug Substitution; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Predictive Value of Tests; Purpura, Thrombocytopenic, Idiopathic; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Reticulated platelets (RP) are young, hyperactive platelets that are increased during situations of enhanced platelet turnover such as acute myocardial infarction (AMI). The dynamics of RP levels after AMI is not established. We aimed to characterize the levels of circulating RP over time in patients with AMI. Patients with AMI treated with ticagrelor or prasugrel who underwent percutaneous coronary intervention (PCI) were tested for circulating RP using flow cytometry with Thiazole orange staining at 3 time points at 2-4 days, 30-60 days and 1 year post PCI. Platelet reactivity was assessed using the VerifyNow P2Y12 assay at these time points (results in platelet reactivity units-PRU). Thirty-five patients were included in the study (mean age 62.6 ± 9.1 years, 82.9 % males). Median RP levels were similar at the first and second time points (17.5 %, IQR 25-75: 10.8-22.4 % and 14.9 %, IQR 25-75: 9.7-26.8 %, respectively; p = 0.75). However, RP levels after 1 year were significantly lower as compared to the first and second time points (10.5 % (IQR 25-75: 5.3-18.1 %), p = 0.005 and p = 0.01, respectively). Residual platelet reactivity was very low at all 3 time points (median PRU 25, IQR 25-75: 7-53) and did not change significantly between them (p = 0.66). No significant correlation was found between levels of RP and PRU at any given time point. RP levels of patients with AMI treated with prasugrel or ticagrelor decrease over time after the acute event. However, RP levels over time do not correlate well with residual platelet reactivity.

Topics: Adenosine; Aged; Blood Platelets; Cohort Studies; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Ticagrelor; Time Factors; Treatment Outcome

While randomized clinical trials have compared clopidogrel with higher potency adenosine diphosphate (ADP) receptor inhibitors among patients with acute myocardial infarction, little is known about the frequency, effectiveness and safety of switching between ADP receptor inhibitors in routine clinical practice.. We studied 11,999 myocardial infarction patients treated with percutaneous coronary intervention at 230 hospitals from April 2010 to October 2012 in the TRANSLATE-ACS study. Multivariable Cox regression was used to compare six-month post-discharge risks of major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, or unplanned revascularization) and Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-defined bleeding between in-hospital ADP receptor inhibitor switching versus continuation of the initially selected therapy. Among 8715 patients treated initially with clopidogrel, 994 (11.4%) were switched to prasugrel or ticagrelor; switching occurred primarily after percutaneous coronary intervention (60.9%) and at the time of hospital discharge (26.7%). Among 3284 patients treated initially with prasugrel or ticagrelor, 448 (13.6%) were switched to clopidogrel; 48.2% of switches occurred after percutaneous coronary intervention and 48.0% at hospital discharge. Switching to prasugrel or ticagrelor was not associated with increased bleeding when compared with continuation on clopidogrel (2.7% vs. 3.3%, adjusted hazard ratio 0.96, 95% confidence interval 0.64-1.42, p=0.82). Switching from prasugrel or ticagrelor to clopidogrel was not associated with increased MACE (8.9% vs. 7.7%, adjusted hazard ratio 1.06, 95% confidence interval 0.75-1.49, p=0.76) when compared with continuation on the higher potency agent.. In-hospital ADP receptor inhibitor switching occurs in more than one in 10 myocardial infarction patients in contemporary practice. In this observational study, ADP receptor inhibitor switching does not appear to be significantly associated with increased hazard of MACE or bleeding.

Topics: Adenosine; Aged; Clopidogrel; Drug Substitution; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Patient Discharge; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proportional Hazards Models; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine

Morphine is recommended in patients with ST-segment-elevation myocardial infarction, including those undergoing primary percutaneous coronary intervention. Suboptimal antiplatelet effect during and after primary percutaneous coronary intervention is associated with increased thrombotic complications. It was hypothesized a potential drug-drug interaction between morphine and antiplatelet agents. We sought to assess platelet inhibition after a loading dose of the currently recommended antiplatelet agents in ST-segment-elevation myocardial infarction patients according to morphine use.. Three hundred patients undergoing primary percutaneous coronary intervention receiving either prasugrel (n = 95) or ticagrelor (n = 205) loading dose had platelet reactivity assessed by VerifyNow 1, 2, and 4 hours after loading dose. Patients treated with morphine (n = 95; 32%) had a higher incidence of vomit (15% versus 2%; P = 0.001). P2Y12 reactivity units 2 hours after the loading dose was 187 (153-221) and 133 (102-165) in patient with and without morphine (P < 0.001); the difference persisted after excluding patients with vomit (P < 0.0001). High residual platelet reactivity (P2Y12 reactivity units ≥ 208) at 2 hours was found in 53% and 29% patients with and without morphine (P < 0.001) and without difference between prasugrel and ticagrelor patients. The independent predictors of high residual platelet reactivity at 2 hours were morphine use (odds ratio, 2.91 [1.71-4.97]; P < 0.0001) and age (odds ratio, 1.03 [1.01-1.05]; P = 0.010). Morphine remained associated with high residual platelet reactivity after propensity score adjustment (c-statistic, 0.68; 95% confidence interval, 0.66-0.70; P = 0.879 for Hosmer-Lemeshow test).. In patients with ST-segment-elevation myocardial infarction, morphine use is associated with a delayed onset of action of the oral antiplatelet agents. This association persisted after adjusting for the propensity to receive morphine and after excluding patients with vomit.

Topics: Acute Disease; Adenosine; Age Factors; Aged; Analgesics, Opioid; Drug Interactions; Electrocardiography; Female; Humans; Male; Middle Aged; Morphine; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Thiophenes; Ticagrelor

Topics: Adenosine; Clinical Trials as Topic; Emergency Medical Services; Humans; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

The recently published Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary Artery (ATLANTIC) trial concluded that prehospital administration of ticagrelor in patients with acute STEMI appeared to be safe but did not improve pre-PCI coronary reperfusion. The ATLANTIC data fully support the PLATO Angiographic Substudy denying early benefit of ticagrelor, and correspond well with lack of immediate clinical benefit including the early PCI "death paradox" in PLATO-USA patients. Finally, there were significantly (p=0.043) more deaths in early ticagrelor ATLANTIC arm (odds ratio 3.18 (1.02-9.90) challenging stent thrombosis reduction. Indeed, ATLANTIC represents an important step for our better understanding of ticagrelor, although the confirmation of the PLATO mortality wonder in an adequately powered PEGASUS (TIMI-54) to be reported in 2015 will be vital for ticagrelor future.

Topics: Adenosine; Clinical Trials as Topic; Drug Administration Schedule; Emergency Medical Services; Humans; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Topics: Adenosine; Gout; Humans; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Ticagrelor; Uric Acid

The newer oral P2Y12 inhibitors prasugrel and ticagrelor have been reported to be more potent and faster-acting antiplatelet agents than clopidogrel. This study aimed to investigate whether prehospital loading with prasugrel or ticagrelor improves early coronary reperfusion as compared to prehospital loading with clopidogrel in a real-world ST-elevation myocardial infarction (STEMI) setting. Over a 70-month period, 3497 patients with on-going STEMI of less than 6 hours and without cardiac arrest or cardiogenic shock underwent primary percutaneous coronary intervention (PPCI) at our centre. The primary endpoint of this study was the proportion of patients who did not meet the criteria for TIMI (Thrombolysis In Myocardial Infarction) flow grade 3 in the infarct-related artery at initial angiography before PPCI. Prehospital loading with prasugrel (n = 883) or ticagrelor (n = 491) did not significantly improve coronary reperfusion as compared to prehospital loading with clopidogrel (n = 1,532) - a TIMI-flow 3 at initial angiography was absent in 71.7 %, 69.0 % and 71.5 % of patients, respectively. Major adverse cardiac event (MACE) rates were low at 30 days (3.4 % to 4.0 %) and did not significantly differ between the different P2Y12 inhibitor regimens. In conclusion, this large observational, non-randomised study is the first to show that prehospital loading with the newer P2Y12 inhibitors does not improve early coronary reperfusion as compared to prehospital loading with clopidogrel in a PPCI cohort excluding cardiac arrest and cardiogenic shock.

Topics: Adenosine; Aged; Clopidogrel; Coronary Angiography; Coronary Circulation; Drug Administration Schedule; Emergency Medical Services; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

In ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) peri-procedural P2Y12 antagonism - although of great importance - is often suboptimal, even with the novel oral antiplatelet agents prasugrel and ticagrelor. The concept of pre-hospital ticagrelor loading, investigated in the recently published Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary Artery (ATLANTIC) trial, appears quite a promising strategy to optimize peri-procedural platelet inhibition and potentially clinical outcome. Implementation of such an approach when treating low risk STEMI patients in 'real life' practice might prove even more beneficial than expected from the ATLANTIC results, given the reported delays from first medical contact to primary PCI performance.

Topics: Adenosine; Electrocardiography; Humans; Myocardial Infarction; Myocardial Reperfusion; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

Topics: Adenosine; Coronary Disease; Humans; Long-Term Care; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Recurrence; Ticagrelor

In addition to P2Y12 receptor antagonism, ticagrelor inhibits adenosine cell uptake. Prior data show that 7-day pretreatment with ticagrelor limits infarct size. We explored the acute effects of ticagrelor and clopidogrel on infarct size and potential long-term effects on heart function.. Rats underwent 30-minute ischemia per 24-hour reperfusion. (1) Ticagrelor (10 or 30 mg/kg) or clopidogrel (12.5 mg/kg) was given via intraperitoneal injection 5 minutes before reperfusion. (2) Rats received ticagrelor acute (intraperitoneal; 30 mg/kg), chronic (oral; 300 mg/kg per day) for 4 weeks starting 1 day after reperfusion or the combination (acute+chronic). Another group received clopidogrel (intraperitoneal [12.5 mg/kg]+oral [62.5 mg/kg per day]) for 4 weeks. (1) Ticagrelor dose-dependently reduced infarct size, 10 mg/kg (31.5%±1.8%; P<0.001) and 30 mg/kg (21.4%±2.6%; P<0.001) versus control (45.3±1.7%), whereas clopidogrel had no effect (42.4%±2.6%). Ticagrelor, but not clopidogrel, increased myocardial adenosine levels, increased phosphorylation of Akt, endothelial NO synthase, and extracellular-signal-regulated kinase 1/2 4 hours after reperfusion and decreased apoptosis. (2) After 4 weeks, left ventricular ejection fraction was reduced in the vehicle-treated group (44.8%±3.5%) versus sham (77.6%±0.9%). All ticagrelor treatments improved left ventricular ejection fraction, acute (69.5%±1.6%), chronic (69.2%±1.0%), and acute+chronic (76.3%±1.2%), whereas clopidogrel had no effect (37.4%±3.7%). Ticagrelor, but not clopidogrel, attenuated fibrosis and decreased collagen-III mRNA levels 4 weeks after ischemia/reperfusion. Ticagrelor, but not clopidogrel, attenuated the increase in proinflammatory tumor necrosis factor-α, interleukin-1β, and interleukin-18, and increased anti-inflammatory 15-epi-lipoxin-A4 levels.. Ticagrelor, but not clopidogrel, administered just before reperfusion protects against reperfusion injury. This acute treatment or chronic ticagrelor for 4 weeks or their combination improved heart function, whereas clopidogrel, despite achieving a similar degree of platelet inhibition, had no effect.

Topics: Adenosine; Administration, Oral; Animals; Apoptosis; Cardiotonic Agents; Clopidogrel; Disease Models, Animal; Dose-Response Relationship, Drug; Fibrosis; Injections, Intraperitoneal; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Purinergic P2Y Receptor Antagonists; Rats, Sprague-Dawley; Signal Transduction; Ticagrelor; Ticlopidine; Time Factors; Ventricular Function, Left; Ventricular Remodeling

We describe a case of a 67-year-old man who required emergency surgery for acute intracranial bleeding after having received a loading dose of aspirin and ticagrelor for an acute ST-elevation myocardial infarction. Before and during the craniocervical decompression, the assessment of platelet function was performed using the Multiplate® analyzer. Biological evaluation of platelet function was consistent with the clinical impression, suggesting that platelet transfusion and desmopressin administration in the presence of ticagrelor had very little, if any, hemostatic effect.

Topics: Adenosine; Aged; Aspirin; Combined Modality Therapy; Deamino Arginine Vasopressin; Fatal Outcome; Hemostatics; Humans; Intracranial Hemorrhages; Male; Myocardial Infarction; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Platelet Transfusion; Purinergic P2Y Receptor Antagonists; Ticagrelor

Recent studies have suggested that ticagrelor 90mg twice daily provides stronger platelet inhibition than prasugrel 10mg once daily in acute coronary syndrome patients undergoing percutaneous coronary intervention.. To compare the effects of ticagrelor 90 mg twice daily and prasugrel 10mg once daily on platelet reactivity in patients with ST-segment elevation myocardial infarction (STEMI), using: the VerifyNow(®) P2Y12 (VN-P2Y12) assay, expressed in P2Y12 reaction units (PRU); measurement of the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI; %); and light transmission aggregometry (LTA), expressed as residual platelet aggregation (RPA; %).. Platelet reactivity was evaluated prospectively using the three assays 30 days after primary PCI in 118 patients with STEMI on a maintenance dose of prasugrel 10mg once daily (n=60) or ticagrelor 90mg twice daily (n=58).. On-treatment platelet reactivity, assessed by the VN-P2Y12 assay, was lower for ticagrelor compared with prasugrel (20.91 ± 4.59 PRU vs. 43.50±6.98 PRU; P=0.008) but was not significantly different when using the more specific VASP-PRI assay (13.05 ± 1.61% vs. 17.44 ± 1.97%; P=0.09) or RPA assessed by LTA (10.49 ± 1.44% vs. 7.20 ± 1.27%; P=0.09).. The difference in platelet reactivity between ticagrelor and prasugrel varies according to the platelet function test in patients with STEMI. The differences observed may be related more to the tests than to the drugs used.

Topics: Adenosine; Blood Platelets; Cell Adhesion Molecules; Drug Administration Schedule; Female; Humans; Male; Microfilament Proteins; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Phosphoproteins; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Predictive Value of Tests; Prospective Studies; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Ticagrelor; Time Factors; Treatment Outcome

Topics: Acute Coronary Syndrome; Adenosine; Cardiac Catheterization; Humans; Mitral Valve Insufficiency; Myocardial Infarction; Percutaneous Coronary Intervention; Polymorphism, Single Nucleotide; Purinergic P2Y Receptor Antagonists; Ticagrelor

Topics: Adenosine; Aged; Aspirin; Female; Humans; Male; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Secondary Prevention; Ticagrelor; Treatment Outcome

Topics: Adenosine; Aspirin; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Ticagrelor

Ticagrelor was daily administered throughout pregnancy to a 37-year-old pregnant woman until 36 weeks of gestation. The patient, with Behçet disease, suffered from a non-ST elevation myocardial infarction 4 months before conception, possibly related to hypertension and tobacco abuse. Pregnancy and postpartum periods were uneventful. She delivered a healthy but small-for-gestational-age term neonate.

Topics: Adenosine; Adult; Aspirin; Drug Therapy, Combination; Female; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Pregnancy; Pregnancy Complications; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Thromboembolism; 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

The current standard of antiplatelet therapy of patients after myocardial infarction includes the P2Y12 receptor antagonists clopidogrel, prasugrel or ticagrelor. This study aimed to compare the antiplatelet effect of clopidogrel, prasugrel and ticagrelor in patients after myocardial infarction. In a single-centre registry the antiplatelet effect of clopidogrel, prasugrel and ticagrelor was investigated by aggregometry in patients after myocardial infarction. To assess the overall capacity of platelet aggregation whole blood was induced with thrombin receptor activating peptide (TRAP; 32 µM). To specifically quantify the effect of P2Y12 antagonists, whole blood was stimulated with 6.4 µM adenosine diphophosphate (ADP). Relative ADP induced aggregation (r-ADP-agg) was defined as the ADP-TRAP ratio to reflect an individual degree of P2Y12-dependent platelet inhibition.Platelet function of 238 patients was analysed [clopidogrel (n=58), prasugrel (n=65), ticagrelor (n=115)]. The r-ADP-agg was 35 ± 14% for patients receiving clopidogrel, 28 ± 10% for patients receiving prasugrel and 26 ± 11% for patients receiving ticagrelor. The r-ADP-agg was significantly lower in patients treated with prasugrel (p=0.0024) or ticagrelor (p<0.0001) compared to clopidogrel. There was no significant difference between patients receiving prasugrel or ticagrelor (p=0.2559). In conclusion, prasugrel and ticagrelor provide a stronger platelet inhibition compared to clopidogrel in patients after myocardial infarction. No significant difference in platelet inhibition was detected between prasugrel and ticagrelor. (registry for patients after Myocardial Infarction Treated with AntiPlatelet agents; DRKS00003146).

Topics: Adenosine; Aged; Aged, 80 and over; Blood Platelets; Clopidogrel; Drug Design; Female; Germany; Humans; Male; Middle Aged; Myocardial Infarction; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Registries; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

A 68 year-old man, initially managed with primary percutaneous coronary intervention (PCI) to the right coronary artery (RCA) for an inferior ST elevation myocardial infarction (STEMI) with residual disease requiring coronary artery bypass graft surgery (CABG), re-presented with chest pain. There were no acute ischaemic changes on ECG and his pain settled with nitrates. A day later, he developed left sided abdominal pain and hypovolaemic shock after straining in the toilet. A subsequent computed tomography (CT) scan of his abdomen revealed an omental bleed. He proceeded to emergency laparotomy, recovered well, and was discharged on aspirin and clopidogrel. Apart from dual antiplatelet therapy with aspirin and ticagrelor, and presumed raised intra-abdominal pressure, there were no other identified risk factors for increased bleeding.

Topics: Adenosine; Aged; Aspirin; Clopidogrel; Gastrointestinal Hemorrhage; Humans; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine

Topics: Adenosine; Clinical Trials as Topic; Clopidogrel; Emergency Medical Services; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticagrelor; Ticlopidine

In a phase III clinical trial (PLATelet inhibition and patient Outcomes, PLATO), ticagrelor provided better clinical outcomes than clopidogrel in patients with acute coronary syndromes. In addition to P2Y12-receptor antagonism, ticagrelor prevents cell uptake of adenosine and has proven able to augment adenosine effects. Adenosine protects the heart against ischemia-reperfusion injury. We compared the effects of clopidogrel and ticagrelor on myocardial infarct size (IS).. Rats received oral ticagrelor (0, 75, 150, or 300 mg/kg/d) or clopidogrel (30 or 90 mg/kg/d) for 7 days and underwent 30-minute coronary artery ligation and 24-hour reperfusion. Area at risk was assessed by blue dye and IS by 2,3,5-triphenyl-tetrazolium-chloride. Cyclooxygenase-2 (COX2) enzyme activity was assessed by ELISA and expression by real-time polymerase chain reaction. Mechanism responsible was explored using adenosine-receptor antagonist (CGS15943, an A2A/A1 antagonist) or cyclooxygenase inhibition by either aspirin (5, 10, or 25 mg/kg) or specific cyclooxygenase-1 (SC560) or COX2 (SC5815) inhibitors. Ticagrelor, dose-dependently, reduced IS, whereas clopidogrel had no effect. Adenosine-receptor antagonism blocked the ticagrelor effect and COX2 inhibition by SC5815, or high-dose aspirin attenuated the IS-limiting effect of ticagrelor, whereas cyclooxygenase-1 inhibition or low-dose aspirin had no effect. Ticagrelor, but not clopidogrel, upregulated COX2 expression and activity. Also this effect was blocked by adenosine-receptor antagonism. Ticagrelor, but not clopidogrel, increased Akt and endothelial nitric oxide synthase phosphorylation.. Ticagrelor, but not clopidogrel, reduces myocardial IS. The protective effect of ticagrelor was dependent on adenosine-receptor activation with downstream upregulation of endothelial nitric oxide synthase and COX2 activity.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine; Adenosine A1 Receptor Antagonists; Adenosine A2 Receptor Antagonists; Animals; Aspirin; Cardiotonic Agents; Clopidogrel; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Drug Evaluation, Preclinical; Enzyme Induction; Lipoxins; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Nitric Oxide Synthase Type III; Pyrazoles; Quinazolines; Rats; Rats, Sprague-Dawley; Receptor, Adenosine A1; Receptor, Adenosine A2A; Ticagrelor; Ticlopidine; Triazoles; Up-Regulation

To evaluate the clinical utility of individualising dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in an all-comers population, including ST-elevation myocardial infarction (STEMI) patients.. Tertiary care single centre registry.. 1008 consecutive PCI patients with stent implantation, without exclusion criteria.. Peri-interventional individualisation of DAPT, guided by multiple electrode aggregometry (MEA), to overcome high on-treatment platelet reactivity (HPR) to ADP-induced (≥50 U) and arachidonic acid (AA)-induced aggregation (>35 U).. The primary efficacy end point was definite stent thrombosis (ST) at 30 days. The primary safety end point was thrombolysis in myocardial infarction (TIMI) major and minor bleeding. Secondary end points were probable ST, myocardial infarction, cardiovascular death and the combined end point: major cardiac adverse event (MACE).. 53% of patients presented with acute coronary syndrome (9% STEMI, 44% non-ST-elevation). HPR to ADP after 600 mg clopidogrel loading occurred in 30% of patients (73±19 U vs 28±11 U; p<0.001) and was treated by prasugrel or ticagrelor (73%), or clopidogrel (27%) reloading (22±12 U; p<0.001). HPR to ADP after prasugrel loading occurred in 2% of patients (82±26 U vs 19±10 U; p<0.001) and was treated with ticagrelor (34±15 U; p=0.02). HPR to AA occurred in 9% of patients with a significant higher proportion in patients with HPR to ADP (22% vs 4%, p<0.001) and was treated with aspirin reloading. Definite ST occurred in 0.09% of patients (n=1); probable ST, myocardial infarction, cardiovascular death and MACE occurred in 0.19% (n=2), 0.09% (n=1) and 1.8% (n=18) of patients. TIMI major and minor bleeding did not differ between patients without HPR and individualised patients (2.6% for both).. Individualisation of DAPT with MEA minimises early thrombotic events in an all-comers PCI population to an unreported degree without increasing bleeding. A randomised multicentre trial utilising MEA seems warranted.. http://www.clinicaltrials.gov; NCT01515345.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Angioplasty, Balloon, Coronary; Aspirin; Blood Platelets; Clopidogrel; Cohort Studies; Coronary Artery Disease; Female; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Precision Medicine; Prospective Studies; Registries; Stents; 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

The ATLANTIC trial compared effects of initiation of ticagrelor at the prehospital (ambulance) or hospital (in the catheterization laboratory) stage of treatment of patients with ST-segment elevation myocardial infarction. Initiation of therapy with ticagrelor at prehospital stage short before percutaneous coronary intervention was safe, but did not improve coronary reperfusion before this procedure. However, earlier administration of ticagrelor significantly reduced the risk of stent thrombosis after percutaneous coronary intervention.

Topics: Adenosine; Coronary Circulation; Emergency Medical Services; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Preoperative Care; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Stents; Thrombosis; Ticagrelor; Time-to-Treatment; Treatment Outcome

Primary percutaneous coronary intervention (PCI) is the treatment of choice for patients presenting with acute ST-segment elevation myocardial infarction (STEMI). However, if catheterization facilities are not immediately available, the effectiveness of PCI can be affected by delays in transfer. Evidence suggests that antiplatelet therapy administered early, preferably in the ambulance during transfer, may provide better and earlier perfusion. Ticagrelor, a direct platelet P2Y12 receptor inhibitor, is indicated for the management of patients with acute coronary syndromes. The ATLANTIC study (NCT01347580; EudraCT 2011-000214-19) is a 30-day international, randomized, parallel-group, placebo-controlled study in male and female patients (aged ≥18 years) who are diagnosed as having STEMI, with intended primary PCI. In total, 1770 patients will be randomized immediately after diagnosis to prehospital administration of ticagrelor 180 mg followed by matching placebo administered in hospital, or prehospital administration of placebo followed by ticagrelor 180 mg administered in hospital. All patients will then receive ticagrelor 90 mg twice daily for 30 days. The coprimary end point is the percentage of patients reaching thrombolysis in myocardial infarction flow grade 3 in the infarct-related artery at initial angiography or achieving ≥70% ST-segment elevation resolution pre-PCI. The primary safety end point is major, life-threatening, or minor bleeding after ticagrelor administration. The results of this study may have an impact on future recommendations for treatment for patients with STEMI.

Topics: Adenosine; Adult; Ambulances; Angioplasty, Balloon, Coronary; Double-Blind Method; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Reperfusion; Patient Selection; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Research Design; Ticagrelor; Young Adult

Cangrelor, a P2Y12 receptor blocker, administered just prior to reperfusion reduced but did not eliminate myocardial infarction in rabbits. Combining cangrelor with ischemic postconditioning offered no additional protection suggesting they protected by a similar mechanism. To determine if cangrelor's protection might be additive to other cardioprotective interventions we tested cangrelor in combination with ischemic preconditioning, cariporide, a sodium-hydrogen exchange blocker, and mild hypothermia.. Open-chest rats underwent 30-min coronary occlusion/2-h reperfusion.. Cangrelor, administered as a bolus (60 μg/kg) 10 min before reperfusion and continued as an infusion (6 μg/kg/min) for the duration of the experiment, decreased infarction from 45.3 % of risk zone in control hearts to 25.0 %. Combining cangrelor and ischemic preconditioning offered no additional protection. Mild hypothermia (32-33 °C) instituted by peritoneal lavage with cold saline just prior to coronary occlusion resulted in 25.2 % infarction, and combining cangrelor and hypothermia nearly halved infarction to 14.1 % of risk zone. Cariporide (0.5 mg/kg) just prior to occlusion resulted in 27.2 % infarction and 15.8 % when combined with cangrelor. Combining cangrelor, hypothermia and cariporide further halved infarction to only 6.3 %. We also tested another P2Y12 inhibitor ticagrelor which is chemically similar to cangrelor. Ticagrelor (20 mg/kg) fed 1 h prior to surgery reduced infarct size by an amount similar to that obtained with cangrelor (25.6 % infarction), and this protective effect was abolished by chelerythrine and wortmannin, thus implicating participation of PKC and PI3-kinase, resp., in signaling.. Cardioprotection from a P2Y12 receptor antagonist can be combined with at least 2 other strategies to magnify the protection. Combining multiple interventions that use different cardioprotective mechanisms could provide powerful protection against infarction in patients with acute coronary thrombosis.

Topics: Adenosine; Adenosine Monophosphate; Animals; Anti-Arrhythmia Agents; Cardiotonic Agents; Guanidines; Hypothermia, Induced; Ischemic Preconditioning, Myocardial; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Purinergic P2Y Receptor Antagonists; Rats; Rats, Sprague-Dawley; Sulfones; Ticagrelor

Topics: Adenosine; Aged; Aged, 80 and over; Angina, Unstable; Cost-Benefit Analysis; Drug Costs; England; Guideline Adherence; Humans; Life Expectancy; Models, Economic; Myocardial Infarction; Practice Guidelines as Topic; Purinergic P2Y Receptor Antagonists; Ticagrelor

Ticagrelor showed significant reductions in myocardial infarctions (MIs) compared to clopidogrel in the Platelet Inhibition and Patient Outcomes (PLATO) trial. However, there was no explanation as to whether there was an equal distribution of benefit throughout acute coronary syndrome (ACS) types.. To ascertain the safety and efficacy of ticagrelor compared to clopidogrel based on the type of ACS index event (ST-segment elevation myocardial infarction [STEMI], non-ST-segment elevation myocardial infarction [NSTEMI] and unstable angina [UA]).. The FDA Complete Response Review (CRR) indicates that when MIs were broken down by index event type, ticagrelor fared better than clopidogrel only in patients with STEMI (136/3496 [4.2%] vs. 184/3530 [5.7%], hazard ratio (HR) 0.74 [0.59-0.93]), whereas patients with NSTEMI and UA showed no significant difference (288/4005 [7.9%] vs. 324/950 [8.9%], HR 0.87 [0.74-1.02] and 76/1549 [5.2%] vs. 75/1563 [5.1%], HR 1.02 [0.75-1.42]). Moreover, STEMI patients receiving early (<24 h) percutaneous coronary intervention (PCI) showed an increase in 30 day MI or cardiovascular (CV) death on ticagrelor compared to clopidogrel, in both the United States (US) and outside-US (OUS) regions (5.0% vs. 1.8% and 3.2% vs. 2.9%, respectively).. Ticagrelor significantly reduced MIs compared to clopidogrel only in STEMI patients, with those receiving early PCI having worse outcomes with ticagrelor. Despite, NSTEMI patients showing no significant reduction in MI with ticagrelor vs. clopidogrel, CV mortality was significantly reduced. In summary, we cannot be sure what is driving the STEMI-MI benefit, the NSTEMI-CV mortality benefit, nor the overall mortality benefit for ticagrelor-treated patients compared to clopidogrel treated patients.

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

Topics: Adenosine; Coronary Thrombosis; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Secondary Prevention; Thiophenes; Ticagrelor; Treatment Outcome

Topics: Acute Coronary Syndrome; Adenosine; Angioplasty, Balloon, Coronary; Clinical Trials as Topic; Clopidogrel; Data Interpretation, Statistical; Humans; Myocardial Infarction; Platelet Aggregation; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Stroke; Ticagrelor; Ticlopidine; Treatment Outcome

Topics: Adenosine; Clopidogrel; Cost-Benefit Analysis; Humans; Models, Theoretical; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Thiophenes; Ticagrelor; Ticlopidine

Topics: Abciximab; Adenosine; Antibodies, Monoclonal; Clopidogrel; Drug Therapy, Combination; Fibrinolytic Agents; Humans; Immunoglobulin Fab Fragments; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Thiophenes; Ticagrelor; Ticlopidine

Little is known about the antiplatelet action of the thienopyridines, clopidogrel and prasugrel, as well as the non-thienopyridine, ticagrelor, in patients suffering from ST-elevation myocardial infarction (STEMI) complicated by cardiogenic shock since systematic comparisons of these antiplatelet agents in this devastating condition are limited so far. This is a report of a patient with STEMI undergoing urgent PCI in cardiogenic shock followed by repeated angioplasty after suffering early stent thrombosis (ST) who showed dual thienopyridine treatment failure of clopidogrel and prasugrel, which was successfully overcome by switching the patient to the non-thienopyridine derivative ticagrelor.

Topics: Adenosine; Aged; Cardiopulmonary Resuscitation; Clopidogrel; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Shock, Cardiogenic; Stents; Thiophenes; Thrombosis; Ticagrelor; Ticlopidine

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

Central adjudication in randomised controlled outcome-driven trials represents a traditional approach to maintain data integrity by applying uniformed rules for assessment of clinical events. It was the purpose of this investigation to determine the patterns of myocardial infarction (MI) adjudication in the TRITON, RECORD, and PLATO trials. We were matching centrally-adjudicated MI's (CAMI's) from the official trial publication with the site-reported MI (SRMI's) count from the Food and Drug Administration's secondary analyses for the investigational compounds prasugrel (TRITON), rosiglitazone (RECORD), and ticagrelor (PLATO). CAMI numbers showed a remarkable discrepancy to SRMI's by more than a doubling of the difference: from 72 to 145 events in TRITON favoring prasugrel (from a hazard ratio [HR]=0.76, p=0.08; to a HR=0.76, p<0.001), and from 44 to 89 events in favour of ticagrelor in PLATO (from a HR=0.94, p=0.095; to a HR=0.84, p<0.001). In contrast, in the RECORD trial, the CAMI count was less than the SRMI count (from 24 to 8 events, from a HR=1.42, p=0.93; to a HR=1.14, p=0.96), in this case diminishing cardiovascular hazards in favour of rosiglitazone. In conclusion, central adjudication in the TRITON, the RECORD, and the PLATO trial turned out to have a critical impact on study outcomes. Trial publications should in the future include site-reported major efficacy and safety endpoints to preserve data integrity. The regulatory authorities should consider independent audits when there is a major disagreement between centrally adjudicated and site reported events influencing the results of a major clinical trial.

Topics: Acute Coronary Syndrome; Adenosine; Cardiovascular Diseases; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Judgment; Metformin; Multicenter Studies as Topic; Myocardial Infarction; Observer Variation; Outcome Assessment, Health Care; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Process Assessment, Health Care; Randomized Controlled Trials as Topic; Rosiglitazone; Stroke; Sulfonylurea Compounds; Thiazolidinediones; Thiophenes; Ticagrelor

Topics: Adenosine; Angina, Unstable; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Thrombosis; Ticagrelor

the objective of the study was to hypothesize on the potential mechanism explaining the surprising mortality benefit of ticagrelor in the PLATO trial.. in PLATO, the mortality reduction (107 deaths) numerically exceeds the myocardial infarction prevention benefit (89 events), making it a hitherto unmatchable achievement of ticagrelor over active comparator. If confirmed, such an impressive mortality advantage will be critical for the further success of ticagrelor to compensate for its otherwise unfavorable safety profile. In fact, such an impressive survival represents an entirely unexpected benefit, which will serve as a key point in the drug approval process and subsequent use in clinical practice.. The potential association of ticagrelor as a promoter of blood adenosine serving as adenosine agonist is assessed.. multiple properties of adenosine, which can be closely matched with both clinical benefits and adverse events after ticagrelor, suggest that this novel pyrimidine is not a pure antiplatelet agent. Unquestionably, ticagrelor potently inhibits platelet activity via established mechanism of P2Y12 receptor blockade, probably chronically increasing blood adenosine levels and ultimately contributing to the vascular outcome benefit observed in PLATO.. future randomized trials of ticagrelor in acute heart failure, sudden death prevention, and treatment of atrial fibrillation are warranted and will expand our understanding of the potential role of adenosine in the outcome benefit after pyrimidines.

Topics: Adenosine; Drug Therapy, Combination; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Ticagrelor; Treatment Outcome

Ticagrelor has been shown to be superior to clopidogrel in patients presenting with acute myocardial infarction who undergo early invasive treatment. We discuss a hitherto unreported use of ticagrelor in the management of a patient resistant to multiple thienopyridines at high risk of stent thrombosis.

Topics: Adenosine; Aged, 80 and over; Cardiac Catheterization; Clopidogrel; Drug-Eluting Stents; Humans; Male; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Thienopyridines; Thrombosis; Ticagrelor; Ticlopidine; Treatment Outcome

The PLATO trial revealed a remarkable advantage of ticagrelor over clopidogrel in ACS patients. Unless the regulatory authorities discover serious flaws with the study, which is unlikely, the drug may substantially change the present landscape of oral antiplatelet therapy, especially in high-risk patients. Despite a somewhat unfavourable safety profile, ticagrelor has a lot of room to compensate for these well-defined side effects based on a documented absolute mortality reduction, solid prevention of MI, and convincing pattern of benefit growing over time.

Topics: Acute Coronary Syndrome; Adenosine; Clinical Trials, Phase III as Topic; Clopidogrel; Humans; Intracranial Hemorrhages; Myocardial Infarction; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Ticagrelor; Ticlopidine; Treatment Outcome

Reperfusion therapy for myocardial infarction is limited by significant re-occlusion rates and less-than-optimal myocardial tissue perfusion. It was the objective of this study to assess and compare the effect of ticagrelor, the first reversibly binding oral P2Y12 receptor antagonist, with that of clopidogrel, in conjunction with thrombolytic therapy, on platelet aggregation, thrombus formation, and myocardial perfusion in a canine model. Thrombus formation was induced by electrolytic injury and blood flow was measured with a Doppler ultrasonic flowmeter. All animals received tissue plasminogen activator (tPA) (1 mg/kg over 20 min); 10 animals received clopidogrel (10 mg/kg IV bolus over 5 min), 10 animals received ticagrelor initiated with a 1-min bolus (75 microg/kg/min), followed by continuous infusion (10 microg/kg/min) for 2 h, and 10 animals received IV saline. Re-occlusion rate and cyclic flow variation decreased with ticagrelor compared to saline groups (p<0.05). Adenosine phosphate (ADP)-induced platelet aggregation decreased with ticagrelor (1.9% +/- 2.67) and clopidogrel (1.11% +/- 2.0) vs. saline (26.3% +/- 23.5, p<0.05) at the end of adjunctive therapy. Bleeding time increased in the clopidogrel compared to the ticagrelor group (p=0.01). Infarct size was reduced with ticagrelor compared to the clopidogrel and saline groups (p<0.05). Blood flow remained significantly below baseline values at 20 min after tPA administration in the saline and clopidogrel groups but not in the ticagrelor group. In conclusion, in a dog coronary thrombosis model, ticagrelor blocks ADP-induced platelet activation and aggregation; prevents platelet-mediated thrombosis; prolongs reperfusion time and reduces re-occlusion and cyclic flow variation; and significantly decreases infarct size and rapidly restores myocardial tissue perfusion.

Topics: Adenosine; Animals; Bleeding Time; Blood Coagulation; Clopidogrel; Coronary Circulation; Coronary Thrombosis; Disease Models, Animal; Dogs; Drug Therapy, Combination; Echocardiography; Female; Fibrinolytic Agents; Laser-Doppler Flowmetry; Male; Myocardial Infarction; Myocardial Reperfusion; Myocardium; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Recurrence; Thrombolytic Therapy; Ticagrelor; Ticlopidine; Time Factors; Tissue Plasminogen Activator

The combination of aspirin and clopidogrel at a loading dose of 300 mg followed by a maintenance dose of 75 mg daily is a well-established antiplatelet therapy for the secondary prevention of thrombotic complications in the settings of acute coronary syndrome and/or percutaneous coronary intervention (PCI). Despite the demonstrated clinical benefits associated with this antiplatelet therapy, there is accumulating evidence that a consistent proportion of patients persist in having high levels of platelet aggregation following standard clopidogrel dose. Importantly, the high platelet reactivity after clopidogrel treatment has been associated with higher risk for cardiovascular ischemic events, including stent thrombosis. This has warranted the need for alternative oral antiplatelet regimens that achieve a higher degree of platelet inhibition. Several functional studies have shown that a higher clopidogrel loading dose (600 mg) compared with standard dose, and novel oral adenosine diphosphate platelet receptor (P2Y12) antagonists compared with clopidogrel achieve a faster onset of action, increased platelet inhibition, and a more predictable drug response. These more favorable pharmacodynamic characteristics are of particular interest in the setting of primary PCI for ST-segment elevation myocardial infarction (STEMI), in which rapid and consistent inhibition of platelet activation and aggregation is desirable for therapeutic success. The present article reviews data on the clinical impact of enhanced P2Y12 inhibition with either higher clopidogrel dosing or new oral antiplatelet agents, including prasugrel and ticagrelor, in the setting of STEMI, focusing on results in the setting of primary PCI.

Topics: Adenosine; Administration, Oral; Angioplasty, Balloon, Coronary; Aspirin; Clopidogrel; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Electrocardiography; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proportional Hazards Models; Purinergic P2Y Receptor Antagonists; Risk Factors; Thiophenes; 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

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Coronary Artery Bypass; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Stroke; Ticagrelor; Ticlopidine

Topics: Adenosine; Antifibrinolytic Agents; Clopidogrel; Drug Therapy, Combination; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Thiophenes; Ticagrelor; Ticlopidine