ticagrelor and ST-Elevation-Myocardial-Infarction

Aspirin loading (chewable or intravenous) as soon as possible after presentation is a class I recommendation by current ST elevation myocardial infarction (STEMI) guidelines. Earlier achievement of therapeutic antiplatelet effects by aspirin loading has long been considered the standard of care. However, the effects of the loading dose of aspirin (alone or in addition to a chronic maintenance oral dose) have not been studied. A large proportion of myocardial cell death occurs upon and after reperfusion (reperfusion injury). Numerous agents and interventions have been shown to limit infarct size in animal models when administered before or immediately after reperfusion. However, these interventions have predominantly failed to show significant protection in clinical studies. In the current review, we raise the hypothesis that aspirin loading may be the culprit. Data obtained from animal models consistently show that statins, ticagrelor, opiates, and ischemic postconditioning limit myocardial infarct size. In most of these studies, aspirin was not administered. However, when aspirin was administered before reperfusion (as is the case in the majority of studies enrolling STEMI patients), the protective effects of statin, ticagrelor, morphine, and ischemic postconditioning were attenuated, which can be plausibly attributable to aspirin loading. We therefore suggest studying the effects of aspirin loading before reperfusion on the infarct size limiting effects of statins, ticagrelor, morphine, and/ or postconditioning in large animal models using long reperfusion periods (at least 24 h). If indeed aspirin attenuates the protective effects, clinical trials should be conducted comparing aspirin loading to alternative antiplatelet regimens without aspirin loading in patients with STEMI undergoing primary percutaneous coronary intervention.

Topics: Animals; Aspirin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Morphine Derivatives; Percutaneous Coronary Intervention; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

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

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

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

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

Few randomized controlled trials (RCTs) have compared ticagrelor to clopidogrel after thrombolytic therapy in patients with ST-segment elevation myocardial infarction (STEMI). To assess the quality of the current evidence, a trial sequential analysis (TSA) of all the available RCTs was performed. A literature search through electronic databases for relevant RCTs was completed. Trial sequential boundaries were applied to the meta-analysis to guard against statistical error, calculate the information size (IS), and assess the quality of the currently available evidence. The safety outcome was bleeding at 30-days and the efficacy outcome was major adverse cardiovascular events at 30-days. There were 3 RCTs with a total of 3999 patients were included. For the safety and efficacy outcomes, there was no difference between the ticagrelor and clopidogrel groups (RR 0.94; 95% CI 0.56-1.60, p = 0.83) and (RR 0.87; 95% CI 0.49-1.52, p = 0.62), respectively. The corresponding TSA revealed an IS of 20,928 and 37,266 for safety and efficacy outcomes, respectively. The Z-curves for both outcomes failed to cross the conventional boundary of significance and TSA boundary, indicating no statistical difference between the ticagrelor and clopidogrel group and lack of firm evidence from the currently available RCTs to draw conclusion. Based on the current available RCTs, there is not enough evidence to support or refute better outcomes with ticagrelor in patients with STEMI treated with thrombolytics. Larger RCTs with enough power are needed before firm recommendations can be applied.

Topics: Clopidogrel; Humans; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; ST Elevation Myocardial Infarction; Thrombolytic Therapy; Ticagrelor

To determine the therapeutic effects of pre-admission ticagrelor in acute ST elevation myocardial infarction after primary percutaneous coronary intervention.. The meta analysis was conducted at the period from the establishment of the database to the February 2018 period, and comprised earlier studies that were selected after comprehensive search of PubMed, Medline, Excerpta Medica dataBASE and Cochrane databases. The studies compared the pre-treatment group (pre-hospital ticagrelor) with the control group (in-hospital ticagrelor) and found differences in primary percutaneous coronary intervention outcomes for sick individuals suffering from acute ST elevation myocardial infarction.. The two studies selected together had 1915 subjects. The rate of stent thrombosis in the control group was higher than in the pre-treatment group (p<0.01), but there were no significant differences in all-cause mortality (p=0.88), myocardial infarction (p=0.17) and stroke (p=0.49).. Pre-hospital ticagrelor decreased the incidence of stent thrombosis in patients with acute ST elevation myocardial infarction who underwent primary percutaneous coronary intervention.

Topics: Emergency Medical Services; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prosthesis Failure; ST Elevation Myocardial Infarction; Stents; Thrombosis; Ticagrelor; Time-to-Treatment

Topics: Acute Coronary Syndrome; Adenosine Monophosphate; Administration, Intravenous; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor

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

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

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

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

Ticagrelor, a new type of P2Y12 receptor antagonist, has been highly recommended to be used in acute coronary syndrome by the latest guideline, but its side effects are not well-known. We seek to illustrate a potential fatal condition, thrombotic thrombocytopenic purpura (TTP), caused by ticagrelor.. An 87-year-old man who had been prescribed with ticagrelor for 2 months after ST-elevation myocardial infarction (STEMI), presented with severe thrombocytopenia, anemia, renal and liver dysfunction, heart failure and fever.. Peripheral blood smear showed schistocytosis, and a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) activity is low, with normal initial coagulation tests, which were compatible with a diagnosis of TTP.. After cessation of ticagrelor and initiation of therapeutic plasma exchange, our patient recovered.. Re-administration of ticagrelor aggravated TTP and led the patient to death.. Clinicians should be aware of the possibility of ticagrelor-induced TTP in patients with a history of recent myocardial infarction; It is of crucial significance to discontinue and never reuse ticagrelor as long as it is suspected to be implicated in TTP.

Topics: ADAMTS13 Protein; Adenosine; Aged, 80 and over; Fatal Outcome; Humans; Male; Plasma Exchange; Purinergic P2Y Receptor Antagonists; Purpura, Thrombotic Thrombocytopenic; ST Elevation Myocardial Infarction; Ticagrelor; Withholding Treatment

Previous studies have shown that ticagrelor is more effective than clopidogrel in platelet inhibition. However, this conclusion remains controversial. Therefore, we performed this meta-analysis to assess the effect of preoperative loading dose ticagrelor and clopidogrel on no-reflow (NRF) during intervention in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (PPCI).. Randomized controlled trials and observational studies were reviewed. The retrieval time was limited from inception to October 1, 2017. The retrieved databases included PubMed, Embase, the Cochrane Library, Web of Science, CBM, CNKI, the VIP database, and the Wang Fang database. RevMan 5.3 software was used for data analysis.. Fourteen randomized controlled trials and one observational study, including 4,162 patients, were included. In these articles, 1,521 patients were in the ticagrelor group (180 mg) and 2,641 patients were in the clopidogrel group (600 mg). The meta-analysis showed that compared with clopidogrel group, preoperative loading dose ticagrelor: 1) significantly reduced the incidence of NRF during PPCI (95% confidence interval [CI]: 0.15, 0.39,. Compared with clopidogrel, loading dose ticagrelor effectively reduced both the occurrence of NRF during PPCI and the incidence of major adverse cardiovascular event in patients with ST-segment elevation myocardial infarction undergoing PPCI. Furthermore, it did not increase the risk of bleeding after PPCI.

Topics: Clopidogrel; Humans; Observational Studies as Topic; Percutaneous Coronary Intervention; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; ST Elevation Myocardial Infarction; Ticagrelor

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion method in patients with ST-segment elevation myocardial infarction (STEMI). In patients with STEMI who cannot undergo timely primary PCI, pharmacoinvasive treatment is recommended, comprising immediate fibrinolytic therapy with subsequent coronary angiography and rescue PCI if needed. Improving clinical outcomes following fibrinolysis remains of great importance for the many patients globally for whom rapid treatment with primary PCI is not possible. For patients with acute coronary syndrome who underwent primary PCI, the PLATO trial demonstrated superior efficacy of ticagrelor relative to clopidogrel. Results in the predefined subgroup of patients with STEMI were consistent with the overall PLATO trial. Patients who received fibrinolytic therapy in the 24 hours before randomization were excluded from PLATO, and there is thus a lack of data on the safety of using ticagrelor in conjunction with fibrinolytic therapy in the first 24 hours after STEMI. The TREAT study addresses this knowledge gap; patients with STEMI who had symptom onset within the previous 24 hours and had received fibrinolytic therapy (of whom 89.4% had also received clopidogrel) were randomized to treatment with ticagrelor or clopidogrel (median time between fibrinolysis and randomization: 11.5 hours). At 30 days, ticagrelor was found to be non-inferior to clopidogrel for the primary safety outcome of Thrombolysis in Myocardial Infarction (TIMI)-defined first major bleeding. Considering together the results of the PLATO and TREAT studies, initiating or switching to treatment with ticagrelor within the first 24 hours after STEMI in patients receiving fibrinolysis is reasonable.

Topics: Global Health; Humans; Incidence; Multicenter Studies as Topic; Platelet Aggregation Inhibitors; Prognosis; Randomized Controlled Trials as Topic; ST Elevation Myocardial Infarction; Survival Rate; Thrombolytic Therapy; Ticagrelor

Recent advances have caused a major shift in the way ST-elevation myocardial infarctions are managed. This review explores the pharmacological and interventional techniques that have evidence for improving outcomes and the landmark trials that have sparked change. The new P2Y

Topics: Absorbable Implants; Adenosine; Blood Vessel Prosthesis; Humans; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Purinergic P2Y Receptor Agonists; ST Elevation Myocardial Infarction; Stents; Ticagrelor

Topics: Absorbable Implants; Acute Coronary Syndrome; Adenosine; Aftercare; Aged, 80 and over; Cardiac Imaging Techniques; Coronary Angiography; Coronary Artery Bypass; Coronary Disease; Diabetic Angiopathies; Drug Therapy, Combination; Fibrinolytic Agents; Fractional Flow Reserve, Myocardial; Graft Occlusion, Vascular; Humans; Out-of-Hospital Cardiac Arrest; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Prosthesis Design; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; ST Elevation Myocardial Infarction; Stents; Thrombectomy; Ticagrelor; Time-to-Treatment; Tissue Scaffolds

The study sought to compare the clinical efficacy and safety of P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous intervention (PPCI).. Limited data exist regarding the comparative efficacy and safety of P2Y12 inhibitors in STEMI patients undergoing PPCI.. Clinical trials enrolling STEMI patients were identified and relevant data was extracted. Major adverse cardiovascular events (MACE) were defined as the composite of all cause mortality, MI, and target vessel revascularization. Network meta-analysis was performed using Bayesian methods.. A total of 37 studies with 88,402 STEMI patients and 5,077 MACE were analyzed. Outcomes at 1 month (22 studies and 60,783 patients) suggest that prasugrel was associated with: lower MACE than clopidogrel (standard dose odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.50 to 0.69; high-dose OR: 0.60, 95% CI: 0.51 to 0.71; upstream OR: 0.79, 95% CI: 0.66 to 0.94), and ticagrelor (standard dose OR: 0.69, 95% CI: 0.56 to 0.84; upstream OR: 0.72, 95% CI: 0.50 to 1.05); lower mortality and MI than clopidogrel and standard ticagrelor; lower stroke risk than standard clopidogrel and standard or upstream ticagrelor; and lower stent thrombosis than standard or upstream clopidogrel. At 1-year (10 studies, n = 40,333) prasugrel was associated with lower mortality and MACE than other P2Y12 inhibitors. MACE was particularly lower with prasugrel in studies where patients received bivalirudin, drug-eluting stents, and but not glycoprotein IIb/IIIa inhibitor.. In STEMI patients undergoing PPCI, prasugrel and ticagrelor are more efficacious than clopidogrel; in addition, prasugrel was superior to ticagrelor particularly in conjunction with bivalirudin and drug-eluting stents.

Topics: Adenosine; Antithrombins; Bayes Theorem; Blood Platelets; Clinical Trials as Topic; Clopidogrel; Coronary Thrombosis; Drug-Eluting Stents; Evidence-Based Medicine; Hirudins; Humans; Markov Chains; Monte Carlo Method; Network Meta-Analysis; Odds Ratio; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Recombinant Proteins; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Ticlopidine; Treatment Outcome

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

Prasugrel and ticagrelor, new P2Y12-ADP receptor antagonists, are associated with greater pharmacodynamic inhibition and reduction of cardiovascular events in patients with an acute coronary syndrome. However, evidence is lacked about the effects of achieving faster and stronger cyclooxygenase inhibition with intravenous lysine acetylsalicylate (LA) compared to oral aspirin. Recently, we demonstrated in healthy volunteers that the administration of intravenous LA resulted in a significantly reduction of platelet reactivity compared to oral aspirin. Loading dose of LA achieves platelet inhibition faster, and with less variability than aspirin. However, there are no data of this issue in patients with an ST-segment elevation myocardial infarction (STEMI). This is a prospective, randomized, multicenter, open platelet function study conducted in STEMI patients. Subjects were randomly assigned to receive a loading dose (LD) of intravenous LA 450 mg plus oral ticagrelor 180 mg, or LD of aspirin 300 mg plus ticagrelor 180 mg orally. Platelet function was evaluated at baseline, 30 min, 1 h, 4 h and 24 h using multiple electrode aggregometry and vasodilator-stimulated phosphoprotein phosphorylation (VASP). The primary endpoint of the study is the inhibition of platelet aggregation (IPA) after arachidonic acid (AA) 0.5 mM at 30 min. Secondary endpoints were the IPA at 1, 4, and 24 h after AA, and non-AA pathways through the sequence (ADP and TRAP). A total of 32 STEMI patients were randomized (16 LA, 16 aspirin). The inhibition of platelet aggregation after AA 0.5 mM at 30 min was greater in subjects treated with LA compared with aspirin: 166 vs. 412 respectively (p = 0.001). This differential effect was observed at 1 h (p = 0.01), but not at 4 and 24 h. Subjects treated with LA presented less variability and faster inhibition of platelet aggregation wit AA compared with aspirin. The administration of intravenous LA resulted in a significantly reduction of platelet reactivity compared to oral aspirin on ticagrelor inhibited platelets in patients with STEMI. Loading dose of LA achieves an earlier platelet inhibition, and with less variability than aspirin.Trial Registration: Unique identifier: NCT02929888; URL: http://www.clinicaltrials.gov.

Topics: Aspirin; Blood Platelets; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

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

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

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

Coronary microvascular dysfunction after acute coronary syndrome is an important predictor of long-term prognosis. Data is lacking on the effects of oral P2Y. Hospitalized non-ST-segment-elevation acute coronary syndrome patients were randomized (1:1) to ticagrelor or clopidogrel. The index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio were obtained using an intracoronary pressure-temperature sensor-tipped wire.. In total, 128 patients were randomized between March 2018 and July 2020. Mean age 59.2±11.8 years, 84% were male, mean Global Registry of Acute Coronary Events score was 93.7±24.5. Intracoronary physiological measurements were obtained in 118 patients (60 ticagrelor, 58 clopidogrel). In the infarct-related artery, the ticagrelor group had lower baseline index of microcirculatory resistance (22.0 [13.0-34.9] versus 27.7 [19.3-29.8];. In non-ST-segment-elevation acute coronary syndrome patients, ticagrelor significantly improved coronary microvascular function before and after PCI compared with clopidogrel.. URL: https://www.anzctr.org.au; Unique identifier: ACTRN12618001610224.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Female; Humans; Male; Microcirculation; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Treatment Outcome

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

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

Ticagrelor provides more rapid, potent, and consistent anti-platelet efficacy than clopidogrel. This randomized trial aimed to evaluate the anti-inflammation effects of ticagrelor versus clopidogrel on thrombus aspirated from the ST-elevation myocardial infarction (STEMI) patients.. A total of 98 patients with STEMI and intended percutaneous coronary intervention (PCI) were randomly assigned to receive clopidogrel (600-mg loading dose) or ticagrelor (180-mg loading dose), of whom 55 with large thrombus burden underwent thrombus aspiration during PCI. Thrombus specimens were successfully aspirated from 49 patients. Finally, 24 patients in the clopidogrel group and 23 in the ticagrelor group completed the study. Inflammatory cells within thrombi were assessed by hematoxylin-eosin and immunohistochemistry stainings.. In patients with undergoing PCI for STEMI, the loading dose ticagrelor regimen was associated with a reduction in inflammatory cell infiltration within thrombus compared with the loading dose clopidogrel regimen.

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

Morphine reduces absorption and delays action onset of potent oral P2Y₁₂ receptor inhibitors in patients with ST-segment elevation myocardial infarction (STEMI). We sought to determine the differential effects of fentanyl compared to morphine on the pharmacodynamics and pharmacokinetics of ticagrelor in STEMI patients undergoing primary percutaneous coronary intervention (PCI).. PERSEUS (NCT02531165) was a prospective, single-center, open-label, randomized controlled study. Patients with STEMI who required analgesia were randomly assigned in a 1:1 ratio to treatment with intravenous fentanyl or morphine after ticagrelor loading dose (LD) administration. The primary endpoint was platelet reactivity at 2 hours after ticagrelor LD assessed by P2Y₁₂ reaction units (PRU).. The study was prematurely stopped in June 2017 after enrolment of 38 out of 56 planned patients. PRU at 2 hours following ticagrelor LD was 173.3 ± 89.7 in the fentanyl group and 210.3 ± 76.4 in the morphine group (p = 0.179). At 4 hours, PRU was significantly lower among patients treated with fentanyl as compared to those treated with morphine (90.1 ± 97.4 vs. 168.0 ± 72.2; p = 0.011). Maximal plasma concentrations of ticagrelor and its active metabolite AR-C124910XX tended to be delayed and numerically lower among patients treated with morphine compared to fentanyl. Total exposures to ticagrelor and AR-C124910XX within 6 hours after ticagrelor LD were numerically greater among patients treated with fentanyl compared to those treated with morphine.. In patients with STEMI undergoing primary PCI, fentanyl did not improve platelet inhibition at 2 hours after ticagrelor pre-treatment compared with morphine. Fentanyl may, however, accelerate ticagrelor absorption and increase platelet inhibition at 4 hours compared to morphine.

Topics: Fentanyl; Humans; Morphine; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; 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

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

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

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

We aimed to demonstrate whether coronary microvascular function is improved after ticagrelor administration compared to clopidogrel administration in STEMI subjects undergoing thrombolysis.. MIRTOS is a multicentre study of ticagrelor versus clopidogrel in STEMI subjects treated with fibrinolysis. We enrolled 335 patients <75 years old with STEMI eligible for thrombolysis, of whom 167 were randomised to receive clopidogrel and 168 to receive ticagrelor together with thrombolysis. Primary outcome was the difference in post-PCI corrected TIMI frame count (CTFC). All clinical events were recorded in a three-month follow-up period. From the 335 patients who were randomised, 259 underwent PCI (129 clopidogrel and 130 ticagrelor) and 154 angiographies were analysable for the study primary endpoint. No significant difference was found between the clopidogrel (n=85) and ticagrelor (n=69) groups for CTFC (24.33±17.35 vs 28.33±17.59, p=0.10). No significant differences were observed in MACE and major bleeding events between randomisation groups (OR 2.0, 95% CI: 0.18-22.2, p=0.99).. Thrombolysis with ticagrelor in patients <75 years old was not able to demonstrate superiority compared to clopidogrel in terms of microvascular injury, while there was no difference between the two groups in MACE and major bleeding events.. ClinicalTrials.gov Identifier: NCT02429271. EudraCT Number 2014-004082-25.

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

Although P2Y12 receptor blockers have become a standard, adjunctive therapy in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), the optimal regimen has not been established. We performed a prospective, open-label, randomized study to investigate the effect of cangrelor administration on platelet function and inflammation in patients with primary PCI (PPCI). Twenty-two patients were randomized to receive either cangrelor and ticagrelor or ticagrelor alone (standard group) before PPCI. Platelet reactivity was evaluated at baseline (before PCI), 10 min and the end of the procedure. At baseline, there was no significant difference in platelet reactivity between both groups, whereas platelets were significantly inhibited at 10 min after initiating cangrelor vs. standard (adenosine-diphosphate-induced aggregation 102.2 ± 24.88 vs. 333.4 ± 63.3, P < 0.05 and thrombin-receptor-activating-peptide-induced aggregation 285.8 ± 86.1 vs. 624.8 ± 106.0, P < 0.05). Lower platelet aggregation in the cangrelor group persisted but the difference was reduced by the end of the procedure. Circulating inflammatory cells, pro-inflammatory cytokines, total elastase, and surrogates of neutrophil extracellular traps (total elastase-myeloperoxidase complexes) were significantly lower in the cangrelor compared to the standard therapy group at 6 h after randomization. There was a trend towards reduction in cardiac damage in the cangrelor group as reflected by the changes in late gadolinium enhancement between 48 h and 3 months after STEMI. Early administration of cangrelor in STEMI patients was associated with more effective platelet inhibition during PPCI and significantly dampened the deleterious inflammatory response compared to standard therapy (NCT03043274).

Topics: Adenosine Monophosphate; Contrast Media; Gadolinium; Humans; Pancreatic Elastase; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Previous studies have confirmed the safety and feasibility of half-dose ticagrelor in Chinese patients with acute coronary syndrome, but currently there is no plan for the use of ticagrelor for Chinese ST-segment elevation myocardial infarction (STEMI) patients.. It is safe and feasible of low-dose ticagrelor in patients with STEMI.. The STEMI patients who were undergoing emergency intervention and taking ticagrelor were enrolled. Patients whose level of platelet aggregation rate (PAR) less than 30% after 7-day treatment with standard-dose ticagrelor were randomly divided into low-dose group (LD group, 45 mg twice daily) and standard-dose group (SD group, 90 mg twice daily). The changes of levels of platelet parameters were compared between the two groups. The incidence of major adverse cardiac events (MACE), bleeding events were compared between the two groups within 6 months of follow-up.. The levels of PAR in the SD group decreased compared with baseline, and was lower than those of LD group at the same time point. The levels of platelet distribution width in both groups decreased from the baseline values (all p < .05) at 1, 3, and 6 months after grouping treatment, but there was no significant difference between the two groups. The incidence of MACE was similar between the two groups of patients. There were decreasing trends in the incidences of minimal bleeding event, minor bleeding event, dyspnea, and gout in the LD group.. It is safe and feasible of low-dose ticagrelor for patients with STEMI based on the monitoring of PAR.

Topics: Adult; Aged; Dose-Response Relationship, Drug; Feasibility Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; ST Elevation Myocardial Infarction; Ticagrelor; Young Adult

To evaluate the efficacy and safety of ticagrelor monotherapy beyond 1 month and up to 24 months vs. standard 12-month dual antiplatelet therapy (DAPT) with aspirin and ticagrelor followed by aspirin monotherapy among ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI) in the GLOBAL LEADERS trial.. We performed a post hoc analysis of STEMI patients in the GLOBAL LEADERS trial comparing experimental ticagrelor monotherapy (1062 patients) with standard 12-month DAPT (1030 patients). We evaluated predefined primary and secondary endpoints in both treatment arms. Rates of net adverse clinical events (NACE), patient-oriented composite endpoints (POCE), and bleeding academic research consortium (BARC)-defined bleeding Type 3 or 5 were also evaluated. At 2 years, there were no significant differences in rates of primary endpoints in patients who had STEMI [0.89 (0.61-1.31)]. There were similar rates of NACE and POCE in both experimental and reference treatment groups at 2 years post-PCI [hazard ratio (HR) 0.96 (0.77-1.20) and 0.96 (0.77-1.21), respectively]. BARC 3 or 5 bleeding events were numerically less in experimental compared to reference treatment groups at 1 year [HR 0.55 (0.27-1.13)] and 2 years [0.61 (0.32-1.16)].. Presentation with STEMI has not influenced the incidence of GLOBAL LEADERS defined primary endpoints. There were no significant differences in rates of NACE, POCE, and BARC bleeding between the two treatment groups up to 2 years of follow-up. Although these findings should be viewed as exploratory, they expand the evidence on potential safety of aspirin-free antiplatelet strategies after PCI in STEMI.

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

This study sought to determine the agreement between cardiac magnetic resonance (CMR) imaging and invasive measurements of fractional flow reserve (FFR) in the evaluation of nonculprit lesions after ST-segment elevation myocardial infarction (STEMI). In addition, we investigated whether fully quantitative analysis of myocardial perfusion is superior to semiquantitative and visual analysis.. The agreement between CMR and FFR in the evaluation of nonculprit lesions in patients with STEMI with multivessel disease is unknown.. Seventy-seven patients with STEMI with at least 1 intermediate (diameter stenosis 50% to 90%) nonculprit lesion underwent CMR and invasive coronary angiography in conjunction with FFR measurements at 1 month after primary intervention. The imaging protocol included stress and rest perfusion, cine imaging, and late gadolinium enhancement. Fully quantitative, semiquantitative, and visual analysis of myocardial perfusion were compared against a reference of FFR. Hemodynamically obstructive was defined as FFR ≤0.80.. Hemodynamically obstructive nonculprit lesions were present in 31 (40%) patients. Visual analysis displayed an area under the curve (AUC) of 0.74 (95% confidence interval [CI]: 0.62 to 0.83), with a sensitivity of 73% and a specificity of 70%. For semiquantitative analysis, the relative upslope of the stress signal intensity time curve and the relative upslope derived myocardial flow reserve had respective AUCs of 0.66 (95% CI: 0.54 to 0.77) and 0.71 (95% CI: 0.59 to 0.81). Fully quantitative analysis did not augment diagnostic performance (all p > 0.05). Stress myocardial blood flow displayed an AUC of 0.76 (95% CI: 0.64 to 0.85), with a sensitivity of 69% and a specificity of 77%. Similarly, MFR displayed an AUC of 0.82 (95% CI: 0.71 to 0.90), with a sensitivity of 82% and a specificity of 71%.. CMR and FFR have moderate-good agreement in the evaluation of nonculprit lesions in patients with STEMI with multivessel disease. Fully quantitative, semiquantitative, and visual analysis yield similar diagnostic performance.

Topics: Aged; Cardiac Catheterization; Coronary Artery Disease; Female; Fractional Flow Reserve, Myocardial; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Perfusion Imaging; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Predictive Value of Tests; Reproducibility of Results; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

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

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

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

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

Topics: Aged; Drug Administration Schedule; Endothelium, Vascular; Female; Follow-Up Studies; Humans; Male; Middle Aged; Netherlands; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Spain; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Treatment Outcome

This prospective (April 2013-December 2020) parallel assignment clinical trial focuses on ST-Elevation Myocardial Infarction (STEMI) patient outcomes. The clinical trial includes 1500 STEMI patients from two hospitals in the Eastern Province of Saudi Arabia. Patients are assigned to one of two groups; the control arm receives conventional therapy with clopidogrel, while in the active arm the Spartan RX CYP2C19 assay is used to determine the *2 genotype. Carriers of a CYP2C19*2 loss-of-function allele receive prasugrel or ticagrelor, while non-carriers are treated with clopidogrel. Follow-up is one year after primary PCI. The primary end point is the number of patients who develop an adverse major cardiovascular event, including recurrent MI, non-fatal stroke, cardiovascular death, or major bleeding one year after PCI.. The risk of stent thrombosis in PCI patients is usually reduced by dual anti-platelet therapy, comprising aspirin and a P2Y12 inhibitor, such as clopidogrel. However, clopidogrel requires activation by the cytochrome P450 enzyme, CYP2C19. Approximately 20% of the population are unable to activate clopidogrel as they possess the CYP2C19*2 loss-of function (LoF) allele. The primary goal of this trial is to study the benefits of treating only those patients that cannot activate clopidogrel with an alternative that has shown to be a more effective platelet inhibitor and does not require bioactivation by the cytochrome P450 enzyme. We expect an improvement in net clinical benefit outcome in the active arm patients, thus supporting pharmacogenetic testing in PCI patients post STEMI.. Trial registration name is "Bedside Testing of CYP2C19 Gene for Treatment of Patients with PCI with Antiplatelet Therapy" (number NCT01823185) retrospectively registered with clinicaltrials.gov on April 4, 2013. This trial is currently at the patient recruitment stage.

Topics: Clinical Decision-Making; Clopidogrel; Coronary Thrombosis; Cytochrome P-450 CYP2C19; Humans; Multicenter Studies as Topic; Patient Selection; Percutaneous Coronary Intervention; Pharmacogenomic Testing; Pharmacogenomic Variants; Platelet Aggregation Inhibitors; Point-of-Care Testing; Polymorphism, Genetic; Prasugrel Hydrochloride; Predictive Value of Tests; Prospective Studies; Randomized Controlled Trials as Topic; Saudi Arabia; ST Elevation Myocardial Infarction; Stents; Ticagrelor; Treatment Outcome

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

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

Topics: Administration, Oral; Analgesics, Opioid; Blood Platelets; Drug Interactions; Fentanyl; Humans; Morphine; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

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

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

In total, 97 acute ST-segment elevation myocardial infarction (STEMI) patients who received an emergency percutaneous coronary intervention (PCI) were enrolled and divided into a ticagrelor group and a clopidogrel group. Thrombolysis in myocardial infarction (TIMI) blood flow and the corrected TIMI frame count (CTFC) were used to assess the blood perfusion of culprit vessels. Thromboelastography (TEG) was used to evaluate the antiplatelet effect of drugs. The results showed that the incidence of TIMI grade III blood flow in the ticagrelor group was significantly higher than that in the clopidogrel group. The CTFC in the anterior descending, circumflex, and right coronary arteries was statistically significantly lower in the ticagrelor group as compared with that in the clopidogrel group. At 2 h and 7 d postdrug treatment, the adenosine diphosphate-induced platelet inhibition rate (ADP%) in the ticagrelor group increased significantly as compared with that in the clopidogrel group, and the platelet aggregation rate of the ADP pathway (MA

Topics: Aged; Clopidogrel; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Ticagrelor

In the ATLANTIC (Administration of Ticagrelor in the catheterization laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery) trial the early use of aspirin, anticoagulation, and ticagrelor coupled with very short medical contact-to-balloon times represent good indicators of optimal treatment of ST-elevation myocardial infarction and an ideal setting to explore which factors may influence coronary reperfusion beyond a well-established pre-hospital system.. This study sought to evaluate predictors of complete ST-segment resolution after percutaneous coronary intervention in ST-elevation myocardial infarction patients enrolled in the ATLANTIC trial. ST-segment analysis was performed on electrocardiograms recorded at the time of inclusion (pre-hospital electrocardiogram), and one hour after percutaneous coronary intervention (post-percutaneous coronary intervention electrocardiogram) by an independent core laboratory. Complete ST-segment resolution was defined as ≥70% ST-segment resolution.. Complete ST-segment resolution occurred post-percutaneous coronary intervention in 54.9% ( n=800/1456) of patients and predicted lower 30-day composite major adverse cardiovascular and cerebrovascular events (odds ratio 0.35, 95% confidence interval 0.19-0.65; p<0.01), definite stent thrombosis (odds ratio 0.18, 95% confidence interval 0.02-0.88; p=0.03), and total mortality (odds ratio 0.43, 95% confidence interval 0.19-0.97; p=0.04). In multivariate analysis, independent negative predictors of complete ST-segment resolution were the time from symptoms to pre-hospital electrocardiogram (odds ratio 0.91, 95% confidence interval 0.85-0.98; p<0.01) and diabetes mellitus (odds ratio 0.6, 95% confidence interval 0.44-0.83; p<0.01); pre-hospital ticagrelor treatment showed a favorable trend for complete ST-segment resolution (odds ratio 1.22, 95% confidence interval 0.99-1.51; p=0.06).. This study confirmed that post-percutaneous coronary intervention complete ST-segment resolution is a valid surrogate marker for cardiovascular clinical outcomes. In the current era of ST-elevation myocardial infarction reperfusion, patients' delay and diabetes mellitus are independent predictors of poor reperfusion and need specific attention in the future.

Topics: Aged; Aspirin; Coronary Angiography; Coronary Circulation; Coronary Vessels; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Ticagrelor; Time-to-Treatment; Treatment Outcome

Recent evidence demonstrates that intravenous morphine significantly reduces absorption and delays onset of action of oral P2Y12 receptor inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). We aimed to assess the influence of intravenous fentanyl compared with morphine on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) in patients undergoing pPCI for STEMI.. Single-centre, prospective, open-label, randomized controlled study that will randomly assign in a 1:1 ratio patients with STEMI undergoing pPCI to receive intravenous fentanyl or morphine following a pre-hospital 180-mg loading dose of ticagrelor (ClinicalTrials.gov Identifier: NCT02531165). Pharmacokinetic and pharmacodynamic analyses will be performed at baseline and 1, 2, 4, 6, and 12 h post-loading dose. Pharmacodynamic assessments will include P2Y12 reaction units (PRU) measured by VerifyNow P2Y12. Pharmacokinetic assessments include determination of maximal observed plasma concentrations, time for maximal plasma concentration, and area under the plasma concentration vs. time curve from time 0 to the last measurable concentration (AUC0-t) for ticagrelor and AR-C124910XX. The primary endpoint is platelet reactivity assessed by PRU at 2 h post ticagrelor loading dose.. PERSEUS will provide randomized data regarding the impact of fentanyl administration, in patients with STEMI undergoing pPCI, on platelet inhibition and ticagrelor absorption and total exposure.

Topics: Administration, Intravenous; Administration, Oral; Analgesics, Opioid; Blood Platelets; Drug Interactions; Fentanyl; Gastrointestinal Absorption; Humans; Morphine; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Receptors, Purinergic P2Y12; ST Elevation Myocardial Infarction; Switzerland; Ticagrelor; Treatment Outcome

We investigated, in the contemporary era of ST-elevation myocardial infarction (STEMI) treatment, the influence of diabetes mellitus (DM) on cardiovascular outcomes, and whether pre-hospital administration of ticagrelor may affect these outcomes in a subgroup of STEMI patients with DM.. DM patients have high platelet reactivity and a prothrombotic condition which highlight the importance of an effective antithrombotic regimen in this high-risk population.. In toal 1,630 STEMI patients enrolled in the ATLANTIC trial who underwent primary percutaneous coronary intervention (PCI) were included. Multivariate analysis was used to explore the association of DM with outcomes and potential treatment-by-diabetes interaction was tested.. A total of 214/1,630 (13.1%) patients had DM. DM was an independent predictor of poor myocardial reperfusion as reflected by less frequent ST-segment elevation resolution (≥70%) after PCI (OR 0.59, 95% CI 0.43-0.82, P < 0.01) and was an independent predictor of the composite 30-day outcomes of death/new myocardial infarction (MI)/urgent revascularization/definite stent thrombosis (ST) (OR 2.80, 95% CI 1.62-4.85, P < 0.01), new MI or definite acute ST (OR 2.46, 95% CI 1.08-5.61, P = 0.03), and definite ST (OR 10.00, 95% CI 3.54-28.22, P < 0.01). No significant interaction between pre-hospital ticagrelor vs in-hospital ticagrelor administration and DM was present for the clinical, electrocardiographic and angiographic outcomes as well as for thrombolysis in myocardial infarction major bleeding.. DM remains independently associated with poor myocardial reperfusion and worse 30-day clinical outcomes. No significant interaction was found between pre-hospital vs in-hospital ticagrelor administration and DM status. Further approaches for the treatment of DM patients are needed.. clinicaltrials.gov identifier: NCT01347580.

Topics: Aged; Diabetes Mellitus; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Treatment Outcome

Morphine adversely impacts the action of oral adenosine diphosphate (ADP)-receptor blockers in ST-segment elevation myocardial infarction (STEMI) patients, and is possibly associated with differing patient characteristics. This retrospective analysis investigated whether interaction between morphine use and pre-percutaneous coronary intervention (pre-PCI) ST-segment elevation resolution in STEMI patients in the ATLANTIC study was associated with differences in patient characteristics and management.. ATLANTIC was an international, multicenter, randomized study of treatment in the acute ambulance/hospital setting where STEMI patients received ticagrelor 180 mg ± morphine. Patient characteristics, cardiovascular history, risk factors, management, and outcomes were recorded.. Opioids (97.6% morphine) were used in 921 out of 1862 patients (49.5%). There were no significant differences in age, sex or cardiovascular history, but more morphine-treated patients had anterior myocardial infarction and left-main disease. Time from chest pain to electrocardiogram and ticagrelor loading was shorter with morphine (both p = 0.01) but not total ischemic time. Morphine-treated patients more frequently received glycoprotein IIb/IIIa inhibitors (p = 0.002), thromboaspiration and stent implantation (both p < 0.001). No significant difference between the two groups was found regarding pre-PCI ≥ 70% ST-segment elevation resolution, death, myocardial infarction, stroke, urgent revascularization and definitive acute stent thrombosis. More morphine-treated patients had an absence of pre-PCI Thrombolysis in Myocardial Infarction (TIMI) 3 flow (85.8% vs. 79.7%; p = 0.001) and more had TIMI major bleeding (1.1% vs. 0.1%; p = 0.02).. Morphine-treatment was associated with increased GP IIb/IIIa inhibitor use, less pre-PCI TIMI 3 flow, and more bleeding. Judicious morphine use is advised with non-opioid analgesics preferred for non-severe acute pain.. clinicaltrials.gov identifier: NCT01347580.

Topics: Adult; Aged; Analgesics, Opioid; Female; Humans; Male; Middle Aged; Morphine; Pain; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Retrospective Studies; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Despite successful restoration of epicardial vessel patency with primary percutaneous coronary intervention, coronary microvascular injury occurs in a large proportion of patients with ST-segment-elevation myocardial infarction, adversely affecting clinical and functional outcome. Ticagrelor has been reported to increase plasma adenosine levels, which might have a protective effect on the microcirculation. We investigated whether ticagrelor maintenance therapy after revascularized ST-segment-elevation myocardial infarction is associated with less coronary microvascular injury compared to prasugrel maintenance therapy.. A total of 110 patients with ST-segment-elevation myocardial infarction received a loading dose of ticagrelor and were randomized to maintenance therapy of ticagrelor (n=56) or prasugrel (n=54) after primary percutaneous coronary intervention. The primary outcome was coronary microvascular injury at 1 month, as determined with the index of microcirculatory resistance in the infarct-related artery. Cardiovascular magnetic resonance imaging was performed during the acute phase and at 1 month.. The primary outcome of index of microcirculatory resistance was not superior in ticagrelor- or prasugrel-treated patients (ticagrelor, 21 [interquartile range, 15-39] U; prasugrel, 18 [interquartile range, 11-29] U; P=0.08). Recovery of microcirculatory resistance over time was not better in patients with ticagrelor versus prasugrel (ticagrelor, -13.9 U; prasugrel, -13.5 U; P=0.96). Intramyocardial hemorrhage was observed less frequently in patients receiving ticagrelor (23% versus 43%; P=0.04). At 1 month, no difference in infarct size was observed (ticagrelor, 7.6 [interquartile range, 3.7-14.4] g, prasugrel 9.9 [interquartile range, 5.7-16.6] g; P=0.17). The occurrence of microvascular obstruction was not different in patients on ticagrelor (28%) or prasugrel (41%; P=0.35). Plasma adenosine concentrations were not different during the index procedure and during maintenance therapy with ticagrelor or prasugrel.. In patients with ST-segment-elevation myocardial infarction, ticagrelor maintenance therapy was not superior to prasugrel in preventing coronary microvascular injury in the infarct-related territory as assessed by the index of microcirculatory resistance, and this resulted in a comparable infarct size at 1 month.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT02422888.

Topics: Aged; Coronary Circulation; Female; Humans; Magnetic Resonance Imaging, Cine; Male; Microcirculation; Middle Aged; Myocardial Reperfusion Injury; Netherlands; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Risk Factors; Spain; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Treatment Outcome; Vascular Resistance

Ticagrelor significantly reduced the incidence of death, myocardial infarction, and stent thrombosis in patients with ST-segment elevation myocardial infarction (STEMI) intended for reperfusion with a primary percutaneous coronary intervention (pPCI). However, the effects of this drug on microvascular perfusion in patients presenting with STEMI have not been evaluated completely.. A total of 298 patients presenting with STEMI were randomized to either ticagrelor 180 mg loading, followed by 90 mg twice daily, or clopidogrel 600 mg loading, followed by 75 mg daily. The primary endpoint was ST-segment resolution at 90 min after pPCI. The secondary endpoints included myocardial blush grade and corrected thrombolysis in myocardial infarction frame count after the procedure. Left ventricular ejection fraction and major adverse cardiac events (MACE) at the 1- and 6-month follow-up time points were also recorded.. There were no significant differences between the two groups with respect to baseline characteristics. Ticagrelor administration resulted in a higher rate of completed ST-segment resolution (58.67 vs. 39.86%, P=0.001), higher myocardial blush grade (2.63±0.64 vs. 2.41±0.71, P=0.005), and lower corrected thrombolysis in myocardial infarction frame count (19.68±7.38 vs. 22.35±8.30, P=0.004). At 6 months, left ventricular ejection fraction was higher (55.01±8.44 vs. 52.34±9.05%, P=0.009) in the ticagrelor group. Kaplan-Meier analysis showed that MACE-free survival had also improved in the ticagrelor group during the 1- and 6-month follow-up time points.. Compared with clopidogrel, ticagrelor improves myocardial perfusion and left ventricular ejection fraction, and reduces the incidence of MACE for STEMI patients undergoing pPCI, with no significant increase in major bleeding.

Topics: Aged; China; Clopidogrel; Coronary Circulation; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Microcirculation; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Progression-Free Survival; Recovery of Function; ST Elevation Myocardial Infarction; Stroke Volume; Ticagrelor; Time Factors; Ventricular Function, Left

The platelet inhibitory effects induced by oral P2Y. This was a prospective, randomized, double-blind, placebo-controlled pharmacodynamic study conducted in patients undergoing primary percutaneous coronary intervention (n=50) who were randomized to treatment with either cangrelor or matching placebo (bolus followed by 2-hour infusion). All patients received ticagrelor 180-mg loading dose administered as crushed tablets at the time of cangrelor/placebo bolus administration. Pharmacodynamic analyses were performed at 8 time points. Pharmacodynamic effects were measured as P2Y. In patients undergoing primary percutaneous coronary intervention, cangrelor is an effective strategy to bridge the gap in platelet inhibition associated with the use of oral P2Y. URL: https://www.clinicaltrials.gov . Unique identifier: NCT03247738.

Topics: Adenosine Monophosphate; Aged; Biomarkers; Blood Platelets; Cell Adhesion Molecules; Double-Blind Method; Drug Therapy, Combination; Female; Florida; Humans; Male; Microfilament Proteins; Middle Aged; Percutaneous Coronary Intervention; Phosphoproteins; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Treatment Outcome

Background Morphine administration is a strong predictor of delayed onset of action of orally administered ticagrelor in patients with ST-segment-elevation myocardial infarction, likely because of impaired gastrointestinal motility. The aim of this study was to evaluate whether the peripheral opioid antagonist methylnaltrexone could improve pharmacodynamics and pharmacokinetics of orally administered ticagrelor in patients with ST-segment-elevation myocardial infarction receiving morphine. Methods and Results The MOVEMENT (Methylnaltrexone to Improve Platelet Inhibition of Ticagrelor in Morphine-Treated Patients With ST-Segment Elevation Myocardial Infarction) trial was a multicenter, prospective, randomized, controlled trial in patients with ST-segment-elevation myocardial infarction treated with morphine and ticagrelor. Upon arrival to the catheterization laboratory, patients were randomized to a blinded intravenous injection of either methylnaltrexone (8 or 12 mg according to weight) or 0.9% sodium chloride. The proportion of patients with high on-treatment platelet reactivity and plasma concentrations of ticagrelor and AR -C124910XX were assessed at baseline (arrival in the catheterization laboratory) and 1 and 2 hours later. A total of 82 patients received either methylnaltrexone (n=43) or placebo (n=39). Median (interquartile range) time from ticagrelor administration to randomization was 41 (31-50) versus 45.5 (37-60) minutes ( P=0.16). Intravenous methylnaltrexone administration did not significantly affect prevalence of high on-treatment platelet reactivity at 2 hours after inclusion, the primary end point, when compared with placebo (54% versus 51%, P=0.84). Plasma concentrations of ticagrelor and its active metabolite, the prespecified secondary end points, did not differ significantly between the groups over time. There was no significant difference in patient self-estimated pain between the groups. Conclusions Methylnaltrexone did not significantly improve platelet reactivity or plasma concentrations of orally administered ticagrelor in patients with ST-segment-elevation myocardial infarction receiving morphine. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02942550.

Topics: Administration, Oral; Aged; Analgesics, Opioid; Blood Platelets; Cardiac Catheterization; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Injections, Intravenous; Male; Middle Aged; Morphine; Naloxone; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Quaternary Ammonium Compounds; Single-Blind Method; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Currently available data indicate that reduction of ticagrelor maintenance dose (MD) 1-3 years after acute myocardial infarction (AMI) not only provides sufficient platelet inhibition but also can improve ticagrelor's safety profile. The aim of this study was to compare the antiplatelet effect of reduced and standard ticagrelor MD in stable patients beginning 1 month after AMI.. In a single-centre, randomized, open-label, active-controlled trial, on Day 30 following AMI, 52 patients (26 in each study arm) were assigned in a 1:1 ratio to receive either reduced (60 mg b.i.d) or standard (90 mg b.i.d) ticagrelor MD for the following 2 weeks. On Day 45 after AMI the antiplatelet effect of ticagrelor was evaluated with the VASP assay and Multiplate, and there were no significant differences in platelet inhibition between patients on reduced vs. standard MD [VASP: 10.4 (5.6-22.2) vs. 14.1 (9.4-22.1) platelet reactivity index; P = 0.30; Multiplate: 30.0 (24.0-39.0) vs. 26.5 (22.0-35.0) U; P = 0.26]. Likewise, no differences were found regarding the prevalence of on-ticagrelor high platelet reactivity between patients on ticagrelor 60 mg b.i.d vs. 90 mg b.i.d (VASP: 4% vs. 8%; P = 0.67; Multiplate: 15% vs. 8%; P = 0.54). Administration of reduced MD resulted in proportionally lower plasma concentrations of ticagrelor and its active metabolite on Day 45 after AMI.. These results suggest that lowering ticagrelor MD 1 month after AMI confers an adequate antiplatelet effect that is comparable to the standard dose. The tested strategy warrants further research to assess its clinical efficacy and safety.. NCT03251859.

Topics: Aged; Blood Platelets; Female; Humans; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Poland; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

High platelet reactivity (HPR) is a risk factor for stent thrombosis, a potentially lethal complication of percutaneous coronary intervention. HPR is also associated with increased risk of myocardial infarction and death in invasively-treated patients with acute coronary syndrome (ACS). HPR occurs even in ACS patients treated with ticagrelor, a state-of-the-art antiplatelet agent, especially during the first hours of treatment. Patient-level pharmacodynamic data obtained from 102 ACS subjects enrolled in two prospective, pharmacodynamic trials were analysed in order to identify clinical features related with increased odds of on-ticagrelor HPR during the first two hours after ticagrelor loading dose in ACS patients. Presence of ST-segment elevation myocardial infarction (versus non-ST-segment elevation ACS) and morphine co-administration were the strongest predictors of HPR at 1 and 2 hours after ticagrelor loading dose according to linear regression analyses, multiple backward stepwise logistic regression analyses and generalized estimating equation model. By pinpointing simple to recognize clinical features, the results of this study facilitate identification of ACS patients who have the highest odds of HPR during the initial phase of treatment with ticagrelor, and who could potentially benefit from alternative treatment strategies.

Topics: Acute Coronary Syndrome; Aged; Female; Humans; Male; Middle Aged; Models, Cardiovascular; Morphine; Percutaneous Coronary Intervention; Platelet Activation; Platelet Aggregation Inhibitors; Prospective Studies; Regression Analysis; Risk Factors; ST Elevation Myocardial Infarction; Thrombosis; Ticagrelor

The efficacy of ticagrelor in the long-term post-ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.. The purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy.. This international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months.. The combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups.. Among patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088).

Topics: Aged; Cause of Death; Clopidogrel; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Long-Term Care; Male; Middle Aged; ST Elevation Myocardial Infarction; Survival Analysis; Thrombolytic Therapy; Ticagrelor; Treatment Outcome

The long-term pharmacodynamic effects of Ticagrelor versus Clopidogrel in patients undergoing early percutaneous coronary intervention (PCI) after fibrinolytic therapy is unknown. From May 2014 to August 2016, 212 patients undergoing PCI within 24 h of Tenecteplase (TNK), Aspirin, and Clopidogrel for ST-elevated myocardial infarction (STEMI) were randomized at four Canadian sites to receive additional Clopidogrel or Ticagrelor initiated prior to PCI. The platelet reactivity units (PRU) were measured with the VerifyNow Assay before study drug administration (baseline), at 4 and 24 h post PCI, and follow-up appointment. A mixed-model analysis with time as the repeated measure and drug as the between-subjects factor was calculated using 2 separate 1 × 4 ANOVAs, with students t-tests used to compare drugs within each time point. Complete clinical follow-up data (median 115.0 days; IQR 80.3-168.8) was available in 50 patients (23.6%) randomized to either Clopidogrel (n = 23) or Ticagrelor (n = 27). Analyses revealed significant decreases in PRU from baseline to 4 h (261.4 vs. 71.7; Mdiff = - 189.7; p < 0.001) to 24 h (71.7 vs. 27.7; Mdiff = - 44.0; p < 0.001) to end of follow-up (27.7 vs.17.9; Mdiff = - 9.9. p = 0.016) for those randomized to Ticagrelor and significant decreases in PRU only from baseline to 4 h (271.3 vs. 200.8; Mdiff = - 70.5, p = < 0.001) in patients receiving Clopidogrel, and a significantly greater proportion of patients with adequate platelet inhibition (PRU < 208) on long-term follow-up (Clopidogrel, 82.6% vs. Ticagrelor, 100.0%; p = 0.038). Our results demonstrate that in patients undergoing PCI within 24 h of fibrinolysis for STEMI, Ticagrelor provides prolonged platelet inhibition compared with Clopidogrel.

Topics: Adenosine; Aged; Clopidogrel; Female; Follow-Up Studies; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Thrombolytic Therapy; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

The potential interactions between prehospital (pre-H) ticagrelor administration and thrombus aspiration (TA) in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) have never been studied. Therefore, we evaluated the potential benefit of TA and pre-H ticagrelor treatment in patients enrolled in the ATLANTIC trial (NCT01347580).. This analysis included 1,630 patients who underwent primary PCI. Multivariate analysis was used to explore the potential association of TA and pre-H treatment to clinical outcomes. Potential interactions between TA and pre-H ticagrelor were also explored.. A total of 941 (57.7%) patients underwent TA. In adjusted multivariate logistic model, pre-H ticagrelor treatment was significantly associated with less frequent new MI or definite stent *thrombosis (ST) (odds ratio [OR] 0.43, 95% CI 0.20-0.92, P=.031), or definite ST (OR 0.26, 95% CI 0.07-0.91, P=.036) at 30 days. Patients treated with TA had higher frequency of Thrombolysis in Myocardial Infarction (TIMI) flow 0-1 compared with no-TA group (80.7% vs 51.9%, P<.0001). TA when also adjusted for TIMI flow 0-1 showed significant association only for higher bailout use of glycoprotein IIb/IIIa inhibitors (OR 1.72, 95% CI 1.18-2.50, P=.004) and more frequent 30-day TIMI major bleeding (OR 2.92, 95% CI 1.10-7.76, P=.032). No significant interactions between TA and pre-H ticagrelor were present for the explored end points.. TA when left to physicians' discretion was used in high-risk patients, was associated with bailout use of glycoprotein IIb/IIIa inhibitors and TIMI major bleeding, and had no impact on 30-day clinical outcomes. Conversely, pre-H ticagrelor treatment predicted lower 30-day rates of ST or new MI without interaction with TA.

Topics: Age Factors; Aged; Combined Modality Therapy; Coronary Angiography; Double-Blind Method; Emergency Medical Services; Female; Humans; Internationality; Male; Middle Aged; Multivariate Analysis; Percutaneous Coronary Intervention; Predictive Value of Tests; Prognosis; Risk Assessment; Sex Factors; ST Elevation Myocardial Infarction; Survival Rate; Ticagrelor; Treatment Outcome

Among patients with STEMI in the ATLANTIC study, pre-hospital administration of ticagrelor improved post-PCI ST-segment resolution and 30-day stent thrombosis. We investigated whether this clinical benefit with pre-hospital ticagrelor differs by ischemic duration.. In a post hoc analysis we compared absence of ST-segment resolution post-PCI and stent thrombosis at 30 days between randomized treatment groups (pre- versus in-hospital ticagrelor) stratified by symptom onset to first medical contact (FMC) duration [≤1 hour (n = 773), >1 to ≤3 hours (n = 772), and >3 hours (n = 311)], examining the interaction between randomized treatment strategy and duration of symptom onset to FMC for each outcome.. Patients presenting later after symptom onset were older, more likely to be female, and have higher baseline risk. Patients with symptom onset to FMC >3 hours had the greatest improvement in post-PCI ST-segment elevation resolution with pre- versus in-hospital ticagrelor (absolute risk difference: ≤1 hour, 2.9% vs. >1 to ≤3 hours, 3.6% vs. >3 hours, 12.2%; adjusted p for interaction = 0.13), while patients with shorter duration of ischemia had greater improvement in stent thrombosis at 30 days with pre- versus in-hospital ticagrelor (absolute risk difference: ≤1 hour, 1.3% vs. >1 hour to ≤3 hours, 0.7% vs. >3 hours, 0.4%; adjusted p for interaction = 0.55). Symptom onset to active ticagrelor administration was independently associated with stent thrombosis at 30 days (adjusted OR 1.89 per 100 minute delay, 95%CI 1.20-2.97, P < .01), but not post-PCI ST-segment resolution (P = .41).. The effect of pre-hospital ticagrelor to reduce stent thrombosis was most evident when given early within 3 hours after symptom onset, with delay in ticagrelor administration after symptom onset associated with higher rate of stent thrombosis. These findings re-emphasize the need for early ticagrelor administration in primary PCI treated STEMI patients.

Topics: Aged; Coronary Angiography; Disease Progression; Double-Blind Method; Electrocardiography; Emergency Medical Services; Female; Humans; Internationality; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Prognosis; Risk Assessment; ST Elevation Myocardial Infarction; Stents; Survival Analysis; Ticagrelor; Time-to-Treatment; Treatment Outcome

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

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

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

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

Topics: Adenosine Monophosphate; Blood Platelets; Drug Therapy, Combination; Humans; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor

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

The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with second-generation drug eluting stents (DESs) is unclear. Because prolonged DAPT is associated with higher bleeding risk and health care costs, establishing optimal DAPT duration is of paramount importance. No other randomized controlled trials have evaluated the safety of shorter DAPT duration in ST-elevation myocardial infarction (STEMI) patients treated with second-generation DESs and latest P2Y12 platelet receptor inhibitors.. Six months of DAPT after Resolute Integrity stent implantation in STEMI patients is not inferior to 12 months of DAPT in clinical outcomes.. The Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation In ST-elevation Myocardial Infarction (DAPT-STEMI) trial is a randomized, multicenter, international, open-label trial designed to examine the safety (noninferiority) of 6-month DAPT after Resolute Integrity stent implantation in STEMI patients compared with 12-month DAPT. Event-free patients on DAPT at 6month will be randomized (1:1 fashion) between single (aspirin only) versus DAPT for an additional 6 months and followed until 2 years after primary percutaneous coronary intervention. The primary end point is a patient-oriented composite endpoint of all-cause mortality, any myocardial infarction, any revascularization, stroke, and major bleeding (net adverse clinical events [NACE]) at 18 months after randomization. To achieve a power of 85% for a noninferiority limit of 1.66, a total of 1100 enrolled patients are required.. The DAPT-STEMI trial aims to assess in STEMI patients treated with second-generation DESs whether discontinuation of DAPT after 6 months of event-free survival is noninferior to routine 12-month DAPT.

Topics: Adenosine; Antithrombins; Cause of Death; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug-Eluting Stents; Europe; Follow-Up Studies; Hirudins; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Period; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Recombinant Proteins; ST Elevation Myocardial Infarction; Survival Rate; Ticagrelor; Time Factors; Treatment Outcome

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

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

ATLANTIC was a randomized study comparing pre- and in-hospital treatment with a ticagrelor loading dose (LD) in ongoing ST-segment elevation myocardial infarction (STEMI). We sought to compare patient characteristics and clinical outcomes in France with other countries participating in ATLANTIC.. The population comprised 1862 patients, 660 (35.4%) from France and 1202 from 12 other countries. The main endpoints were reperfusion (≥70% ST-segment elevation resolution) and TIMI flow grade 3 before (co-primary endpoints) and after percutaneous coronary intervention (PCI). Other endpoints included a composite ischaemic endpoint (death/myocardial infarction/stroke/urgent revascularization/definite stent thrombosis) and bleeding events at 30days.. In France, median times from first LD to angiography and between first and second LDs were 49 and 35min, respectively, and were similar to other countries. French patients were younger (mean 58.7 vs 61.9years, p<0.0001) and characterized by a higher rate of radial access (89.9% vs 54.8%, p<0.0001), more frequent use of pre-hospital glycoprotein (GP) IIb/IIIa inhibitors (14.1% vs 3.1%, p<0.0001) and intravenous enoxaparin (57.3% vs 10.1%, p<0.0001). In France, as in other countries, the co-primary endpoints did not differ between the two randomization groups. The composite ischaemic endpoint was numerically lower in France (3.3% vs 5.1%, p=0.07), with a lower mortality (1.4% vs 3.3%, p=0.01). PLATO major bleeding was numerically less frequent in France (1.8% vs 3.2%, p=0.07).. The French population appears to have better outcomes than the rest of the study population, and seems related to differences in demographics and management characteristics.. ClinicalTrials.gov (NCT01347580).

Topics: Adenosine; Aged; Emergency Medical Services; Female; France; Humans; Male; Middle Aged; Population Surveillance; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Topics: Administration, Oral; Blood Platelets; Diabetes Mellitus; Drug Resistance; Humans; Hypoglycemic Agents; Insulin; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Patients undergoing PCI early after fibrinolytic therapy are at high risk for both thrombotic and bleeding complications. We sought to assess the pharmacodynamic effects of ticagrelor versus clopidogrel in the fibrinolytic-treated STEMI patients undergoing early PCI.. Patients undergoing PCI within 24 hours of tenecteplase (TNK), aspirin, and clopidogrel for STEMI were randomized to receive additional clopidogrel 300 mg followed by 75 mg daily or ticagrelor 180 mg followed by 90 mg twice daily. The platelet reactivity units (PRU) were measured with the VerifyNow Assay before study drug administration (baseline) at 4 and 24 hours post-PCI. The primary end point was PRU ≤208 at 4 hours. A total of 140 patients (74 in ticagrelor and 66 in clopidogrel group) were enrolled. The mean PRU values at baseline were similar for the 2 groups (257.8±52.9 vs 259.5±56.7, P=.85, respectively). Post-PCI, patients on ticagrelor, compared to those on clopidogrel, had significantly lower PRU at 4 hours (78.7±88 vs 193.6±86.5, respectively, P<.001) and at 24 hours (34.5±35.0 and 153.5±75.5, respectively, P<.001). The primary end point was observed in 87.8% (n=65) in the ticagrelor-treated patients compared to 57.6% (n=38) of clopidogrel-treated patients, P<.001.. Fibrinolysis-treated STEMI patients who received clopidogrel and aspirin at the time of fibrinolysis and were undergoing early PCI frequently had PRU >208. In this high-risk population, ticagrelor provides more prompt and potent platelet inhibition compared with clopidogrel (Funded by Astra Zeneca; NCT01930591, https://clinicaltrials.gov/ct2/show/NCT01930591).

Topics: Adenosine; Blood Platelets; Clopidogrel; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Activation; Platelet Aggregation Inhibitors; Preoperative Care; Prognosis; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Thrombolytic Therapy; Ticagrelor; Ticlopidine; Time Factors

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

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

Dual anti-platelet therapy represents standard care for treating patients with ST-segment elevation myocardial infarction (STEMI). Ticagrelor is a direct-acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation.. To evaluate whether chewing a loading dose (LD) of ticagrelor, 180 mg, vs traditional oral administration of an equal dose enhances platelet inhibition at 30 minutes and 1 hour after LD administration in patients with STEMI.. A randomized clinical trial was conducted in adults aged 30 to 87 years from May to October 2016 in a large tertiary care center. Analyses were intention-to-treat.. Fifty patients with STEMI were randomized to either chewing an LD of ticagrelor, 180 mg, or standard oral administration of an equal dose.. P2Y12 reaction units were evaluated using VerifyNow (Accumentrics) at baseline, 30 minutes, 1 hour, and 4 hours after LD.. Baseline characteristics were similar in both groups. The mean (SD) of P2Y12 reaction units in the chewing group compared with the standard group at baseline, 30 minutes, 1 hour, and 4 hours after ticagrelor LD were 224 (33) vs 219 (44) (95% CI, -16.77 to 27.73; P = .26), 168 (78) vs 230 (69) (95% CI, -103.77 to -19.75; P = .003), 106 (90) vs 181 (89) (95% CI, -125.15 to -26.29; P = .005), and 43 (41) vs 51 (61) (95% CI, -36.34 to 21.14; P = .30), respectively. Platelet reactivity in the chewing group was significantly reduced by 24% at 30 minutes after LD (95% CI, 19.75 to 103.77; P = .001). The relative inhibition of platelet aggregation in the chewing vs the standard group were 51% vs 10% (95% CI, 13.69 to 67.67; P = .005) at 1 hour and 81% vs 76% (95% CI, -12.32 to 16.79; P = .24) at 4 hours, respectively. Major adverse cardiac and cardiovascular event rate at 30 days was low (4%) and occurred in 1 patient in each group (95% CI, 0.06 to 16.93; P > .99).. Chewing an LD of ticagrelor, 180 mg, in patients with STEMI is feasible and facilitates better early platelet inhibition compared with a standard oral LD. Larger studies are warranted to see if our preliminary findings translate into clinical outcomes.. clinicaltrials.gov Identifier: NCT02725099.

Topics: Administration, Oral; Aged; Aspirin; Deglutition; Drug Therapy, Combination; Feasibility Studies; Female; Humans; Intention to Treat Analysis; Male; Mastication; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Early reperfusion of the occluded coronary artery during acute myocardial infarction is considered crucial for reduction of infarcted mass and recovery of ventricular function. Effective microcirculation and the balance between protective and harmful lymphocytes may have roles in reperfusion injury and may affect final ventricular remodeling.. BATTLE-AMI is an open-label, randomized trial comparing the effects of four therapeutic strategies (rosuvastatin/ticagrelor, rosuvastatin/clopidogrel, simvastatin plus ezetimibe/ticagrelor, or simvastatin plus ezetimibe/clopidogrel) on infarcted mass and left ventricular ejection fraction (LVEF) (blinded endpoints) in patients with ST-segment elevation myocardial infarction submitted to fibrinolytic therapy before coronary angiogram (pharmacoinvasive strategy). All patients (n = 300, 75 per arm) will be followed up for six months. The effects of treatment on subsets of B and T lymphocytes will be determined by flow-cytometry/ELISPOT and will be correlated with the infarcted mass, LVEF, and microcirculation perfusion obtained by cardiac magnetic resonance imaging. The primary hypothesis is that the combined rosuvastatin/ticagrelor therapy will be superior to other therapies (particularly for the comparison with simvastatin plus ezetimibe/clopidogrel) for the achievement of better LVEF at 30 days (primary endpoint) and smaller infarcted mass (secondary endpoint) at 30 days and six months. The trial will also evaluate the improvement in the immune/inflammatory responses mediated by B and T lymphocytes. Omics field (metabolomics and proteomics) will help to understand these responses by molecular events.. BATTLE-AMI is aimed to (1) evaluate the role of subsets of lymphocytes on microcirculation improvement and (2) show how the choice of statin/antiplatelet therapy may affect cardiac remodeling after acute myocardial infarction with ST elevation.. ClinicalTrials.gov, NCT02428374 . Registered on 28 September 2014.

Topics: Adenosine; Anti-Inflammatory Agents; B-Lymphocytes; Biomarkers; Brazil; Clinical Protocols; Clopidogrel; Coronary Angiography; Drug Therapy, Combination; Enzyme-Linked Immunospot Assay; Ezetimibe; Female; Flow Cytometry; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation Mediators; Magnetic Resonance Imaging; Male; Metabolomics; Platelet Aggregation Inhibitors; Proteomics; Research Design; Rosuvastatin Calcium; Simvastatin; ST Elevation Myocardial Infarction; Stroke Volume; T-Lymphocytes; Thrombolytic Therapy; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling

A pharmacodynamic comparison between ticagrelor and prasugrel after fibrinolytic therapy has not yet been performed.. In the single-center SAMPA trial, 50 consecutive STEMI patients previously treated with clopidogrel and undergoing a pharmacoinvasive strategy were randomized to either a ticagrelor (n=25) 180mg loading dose followed by 90mg bid, or a prasugrel (n=25) 60mg loading dose followed by 10mg/day, initiated after fibrinolytic therapy but before angiography. Platelet reactivity was assessed with the VerifyNow P2Y. Mean times from fibrinolysis to prasugrel or ticagrelor administration were 11.1±6.9 and 13.3±6.3h, respectively (p=0.24). The values of PRU decreased significantly from baseline to 2h (all p<0.001) and from 2h to 6h (all p<0.001) in both groups. There was no difference in PRU values between 6h and 24h. The mean PRU values at 0, 2, 6, and 24h were 234.9, 127.8, 45.4, and 48.0 in the prasugrel group and 233.1, 135.1, 67.7, and 56.9 in the ticagrelor group, respectively. PRU values did not significantly differ between groups at any time period of the study.. In patients with STEMI treated with fibrinolytic therapy, platelet inhibition after clopidogrel is suboptimal and can be further increased with more potent agents. Ticagrelor and prasugrel demonstrated a similar extent of P2Y

Topics: Adenosine; Coronary Angiography; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Thrombolytic Therapy; Ticagrelor; Time Factors; Treatment Outcome

The main objective of the present randomized pilot study was to explore the effects of upstream prasugrel or ticagrelor or clopidogrel for patients with ST-segment-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).. Administration of clopidogrel "as soon as possible" has been advocated for STEMI. Pretreatment with prasugrel and ticagrelor may improve reperfusion. Currently, the angiographic effects of upstream administration of these agents are poorly understood.. A total of 132 patients with STEMI within the first 12 hr of chest pain referred to primary angioplasty were randomized to upstream clopidogrel (600 mg), prasugrel (60 mg), or ticagrelor (180 mg) while still in the emergency room. All patients underwent protocol-mandated thrombus aspiration.. Macroscopic thrombus material was retrieved in 79.5% of the clopidogrel group, 65.9% of the prasugrel group, and 54.3% of the ticagrelor group (P = 0.041). At baseline angiography, large thrombus burden was 97.7% vs. 87.8% vs. 80.4% in the clopidogrel, prasugrel, and ticagrelor groups, respectively (P = 0.036). Also, at baseline, 97.7% presented with an occluded target vessel in the clopidogrel group, 87.8% in the prasugrel group and 78.3% in the ticagrelor group (P = 0.019). At the end of the procedure, the percentages of patients with combined TIMI grade III flow and myocardial blush grade III were 52.3% for clopidogrel, 80.5% for prasugrel, and 67.4% for ticagrelor (P = 0.022).. In patients with STEMI undergoing primary PCI within 12 hr, upstream clopidogrel, prasugrel or ticagrelor have varying angiographic findings, with a trend toward better results for the latter two agents. © 2015 Wiley Periodicals, Inc.

Topics: Adenosine; Aged; Angioplasty, Balloon, Coronary; Brazil; Clopidogrel; Coronary Angiography; Drug Administration Schedule; Emergency Medical Services; Female; Humans; Male; Middle Aged; Pilot Projects; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Predictive Value of Tests; Prospective Studies; ST Elevation Myocardial Infarction; Thrombectomy; Ticagrelor; Ticlopidine; Time Factors; Time-to-Treatment; Treatment Outcome

The aim of this landmark exploratory analysis, ATLANTIC-H(24), was to evaluate the effects of pre-hospital ticagrelor during the first 24 h after primary percutaneous coronary intervention (PCI) in the ATLANTIC (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery) study.. The ATLANTIC trial in patients with ongoing ST-segment elevation myocardial infarction showed that pre-hospital ticagrelor was safe but did not improve pre-PCI coronary reperfusion compared with in-hospital ticagrelor. We hypothesized that the effect of pre-hospital ticagrelor may not have manifested until after PCI due to the rapid transfer time (31 min).. The ATLANTIC-H(24) analysis included 1,629 patients who underwent PCI, evaluating platelet reactivity, Thrombolysis In Myocardial Infarction flow grade 3, ≥ 70% ST-segment elevation resolution, and clinical endpoints over the first 24 h.. Following PCI, largest between-group differences in platelet reactivity occurred at 1 to 6 h; coronary reperfusion rates numerically favored pre-hospital ticagrelor, and the degree of ST-segment elevation resolution was significantly greater in the pre-hospital group (median, 75.0% vs. 71.4%; p = 0.049). At 24 h, the composite ischemic endpoint was lower with pre-hospital ticagrelor (10.4% vs. 13.7%; p = 0.039), as were individual endpoints of definite stent thrombosis (p = 0.0078) and myocardial infarction (p = 0.031). All endpoints except death (1.1% vs. 0.2%; p = 0.048) favored pre-hospital ticagrelor, with no differences in bleeding events.. The effects of pre-hospital ticagrelor became apparent after PCI, with numerical differences in platelet reactivity and immediate post-PCI reperfusion, associated with reductions in ischemic endpoints, over the first 24 h, whereas there was a small excess of mortality. (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery [ATLANTIC, NCT01347580]).

Topics: Adenosine; Adult; Aged; Ambulances; Coronary Thrombosis; Double-Blind Method; Emergency Medical Services; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Recurrence; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Time-to-Treatment; Treatment Outcome

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

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

Microvascular injury is present in a large proportion of patients with ST-elevation myocardial infarction (STEMI) despite successful revascularization. Ticagrelor potentially mitigates this process by exerting additional adenosine-mediated effects. This study aims to determine whether ticagrelor is associated with a better microvascular function compared to prasugrel as maintenance therapy after STEMI. A total of 110 patients presenting with STEMI and additional intermediate stenosis in another coronary artery will be studied after successful percutaneous coronary intervention (PCI) of the infarct-related artery. Patients will be randomized to treatment with ticagrelor or prasugrel for 1 year. FFR-guided PCI of the non-infarct-related artery will be performed at 1 month. Microvascular function will be assessed by measurement of the index of microcirculatory resistance (IMR) in the infarct-related artery and non-infarct-related artery, immediately after primary PCI and after 1 month. The REDUCE-MVI study will establish whether ticagrelor as a maintenance therapy may improve microvascular function in patients after revascularized STEMI.

Topics: Adenosine; Cardiac Catheterization; Clinical Protocols; Fractional Flow Reserve, Myocardial; Humans; Microcirculation; Myocardial Reperfusion Injury; Netherlands; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Research Design; Spain; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vascular Resistance

PRIVATE-ATLANTIC (P2Y12 Receptor Inhibition with VASP Testing using Elisa kit during the ATLANTIC study) is a pre-specified substudy of the randomised, double-blind ATLANTIC trial in patients with ST-segment elevation myocardial infarction, designed to help interpret the main trial results. The primary objective of ATLANTIC was to assess coronary reperfusion prior to percutaneous coronary intervention (PCI) with pre- vs in-hospital ticagrelor 180 mg loading dose (LD). PRIVATE-ATLANTIC assessed platelet inhibition in 37 patients by measurement of vasodilator-associated stimulated phosphoprotein (VASP) platelet reactivity index (PRI) and VerifyNow platelet reactivity units (PRU) before angiogram (T1), immediately after PCI (T2), 1 (T3), and 6 (T4) hours (h) after PCI, and before next study drug administration (T5). The median time difference between the two ticagrelor LD was 41 minutes. Platelet reactivity was unaffected at T1 when measured by VASP-PRI (89.8 vs 93.9 % for pre- and in-hospital ticagrelor, respectively; p = 0.18) or PRU (239 vs 241; p = 0.82). Numerical differences were apparent at T2 and maximal at T3. Morphine administration significantly delayed onset of platelet inhibition at T3 (VASP-PRI 78.2 vs 23.4 % without morphine; p = 0.0116) and T4 (33.1 vs 11.0 %; p = 0.0057). In conclusion, platelet inhibition in ATLANTIC was unaffected by pre-hospital ticagrelor administration at the time of initial angiogram due to the short transfer delay. The maximum difference in platelet inhibition was detected 1 h after PCI (T3). Morphine administration was associated with delayed onset of action of ticagrelor and appeared more important than timing of ticagrelor administration.

Topics: Adenosine; Blood Platelets; Combined Modality Therapy; Double-Blind Method; Drug Administration Schedule; Humans; Morphine; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor

Third-generation P2Y12 antagonists (prasugrel and ticagrelor) are recommended in guidelines on ST-segment elevation myocardial infarction. Mechanisms translating their more potent antiplatelet activity into improved clinical outcomes versus the second-generation P2Y12 antagonist clopidogrel are unclear. The aim of this post hoc analysis of the Complete Versus Lesion-Only PRImary PCI Trial-CMR (CvLPRIT-CMR) substudy was to assess whether prasugrel and ticagrelor were associated with reduced infarct size compared with clopidogrel in patients undergoing primary percutaneous coronary intervention.. CvLPRIT-CMR was a multicenter, prospective, randomized, open-label, blinded end point trial in 203 ST-segment elevation myocardial infarction patients with multivessel disease undergoing primary percutaneous coronary intervention with either infarct-related artery-only or complete revascularization. P2Y12 inhibitors were administered according to local guidelines. The primary end point of infarct size on cardiovascular magnetic resonance was not significantly different between the randomized groups. P2Y12 antagonist administration was not randomized. Patients receiving clopidogrel (n=70) compared with those treated with either prasugrel or ticagrelor (n=133) were older (67.8±12 versus 61.5±10 years, P<0.001), more frequently had hypertension (49% versus 29%, P=0.007), and tended to have longer symptom-to-revascularization time (234 versus 177 minutes, P=0.05). Infarct size (median 16.1% [quartiles 1-3, 10.5-27.7%] versus 12.1% [quartiles 1-3, 4.8-20.7%] of left ventricular mass, P=0.013) and microvascular obstruction incidence (65.7% versus 48.9%, P=0.022) were significantly greater in patients receiving clopidogrel. Infarct size remained significantly different after adjustment for important covariates using both generalized linear models (P=0.048) and propensity score matching (P=0.025).. In this analysis of CvLPRIT-CMR, third-generation P2Y12 antagonists were associated with smaller infarct size and lower microvascular obstruction incidence versus the second-generation P2Y12 antagonist clopidogrel for ST-segment elevation myocardial infarction.. URL: http://www.isrctn.com/ISRCTN70913605.

Topics: Adenosine; Aged; Clopidogrel; Coronary Angiography; Coronary Stenosis; Drug Administration Schedule; Female; Humans; Magnetic Resonance Angiography; Male; Microvessels; Middle Aged; Myocardial Revascularization; Organ Size; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

We sought to assess the impact of different oral P2Y12 receptor inhibitors on residual thrombus and reperfusion indexes in ST-segment elevation myocardial infarction patients enrolled in the COCTAIL II trial, which included 128 primary percutaneous coronary interventions randomized to intracoronary vs. intralesion abciximab bolus with or without thrombectomy.. Patients were divided into three groups: clopidogrel (n = 44), prasugrel (n = 45) and ticagrelor (n = 39). Residual intra-stent thrombus was quantified by optical coherence tomography using both the number of cross-sections with thrombus area more than 10% and thrombus volume. Reperfusion indexes included thrombolysis in myocardial infarction (TIMI) flow, corrected TIMI frame count, myocardial blush grade (MBG) and complete ST-segment resolution (≥70%).. In the prasugrel group, optical coherence tomography depicted a lower percentage of cross-sections with residual thrombus area more than 10% [4.0 (1.0-8.5)], as compared with clopidogrel [8.0 (1.0-15.0), P = 0.011] and ticagrelor [7.0 (3.0-13.5), P = 0.026].A higher thrombus volume was found in the clopidogrel group 4.0 mm(2.7-6.2) as compared with the prasugrel group [2.8 mm(1.8-4.4), P = 0.023], whereas the other between-group comparisons yield no significant differences. The frequency of MBG 3 was higher in the prasugrel group (73.3%) as compared with clopidogrel (45.5%) and ticagrelor [(56.4%), P = 0.027]. Final TIMI flow, TIMI frame count and ST resolution were not significantly different across the three groups (P = 0.423, 0.179 and 0.848, respectively). At multivariate analysis, pretreatment with prasugrel was independently associated with MBG 3 (odds ratio = 3.93; 95% confidence interval = 1.01-15.39).. Prasugrel loading dose was associated with a lower percentage of cross-sections with residual thrombus area more than 10% as compared with both clopidogrel and ticagrelor, although intrastent thrombus volume was not significantly different between prasugrel and ticagrelor.The frequency of MBG 3 was the only reperfusion index that was significantly more prevalent in prasugrel treated group as compared with clopidogrel and ticagrelor groups.

Topics: Abciximab; Adenosine; Administration, Oral; Aged; Aged, 80 and over; Antibodies, Monoclonal; Clopidogrel; Coronary Angiography; Electrocardiography; Female; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Myocardial Reperfusion; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Stents; Thrombectomy; Thrombosis; Ticagrelor; Ticlopidine; Tomography, Optical Coherence

Ticagrelor has shown greater, more rapid and more consistent platelet inhibition than clopidogrel. However, the superiority of ticagrelor for preventing ischaemic damage in STEMI patients has not been proven. The aim of this trial was to assess whether ticagrelor is superior to clopidogrel in preventing microvascular injury in ST-elevation myocardial infarction (STEMI).. Patients with STEMI underwent prospective random assignment to receive a loading dose (LD) of clopidogrel 600 mg or ticagrelor 180 mg (1:1 ratio) before primary percutaneous coronary intervention (PCI). As the primary endpoint, the index of microcirculatory resistance (IMR) was measured immediately after primary PCI. The secondary endpoint was the infarct size estimated from the wall motion score index (WMSI). A total of 76 patients were enrolled (clopidogrel group=38, ticagrelor group=38). The IMR in the ticagrelor group was significantly lower than that in the clopidogrel group (22.2±18.0 vs. 34.4±18.8 U, p=0.005). Cardiac enzymes were less elevated in the ticagrelor group than in the clopidogrel group (CK peak; 2,651±1,710 vs. 3,139±2,698 ng/ml, p=0.06). Infarct size, estimated by WMSI, was not different between the ticagrelor and clopidogrel groups at baseline (1.55±0.30 vs. 1.61±0.29, p=0.41) or after three months (1.42±0.33 vs. 1.47±0.33, p=0.57).. In patients with STEMI treated by primary PCI, a 180 mg LD of ticagrelor might be more effective in reducing microvascular injury than a 600 mg LD of clopidogrel, as demonstrated by IMR immediately after primary PCI.

Topics: Adenosine; Aged; Clopidogrel; Creatine Kinase; Echocardiography; Female; Humans; Male; Microvessels; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Severity of Illness Index; ST Elevation Myocardial Infarction; Ticagrelor; Ticlopidine; Vascular Resistance

To evaluate in a real-world primary percutaneous coronary intervention (pPCI) registry the impact of the evolution of evidence-based treatments on prognosis.. STEMI patients undergoing pPCI at the University Hospital of Trieste, Italy, were enrolled. The first cohort (old treatments cohort) included STEMI patients treated between January-2007 and December-2012, and the second cohort (new treatments cohort), between January-2013 and December-2020. Inverse Probability of Treatment Weighting (IPTW) Cox regression models as well as multivariable Cox regression models were performed to assess the risk of a composite primary endpoint (PE) of all cause death, reinfarction and re-PCI at 5 years.. A total of 2425 STEMI patients were enrolled. At multivariable Cox regression, the new-treatments cohort had lower risk of PE and mortality. Weighted (IPTW) Cox proportional hazard models confirmed the lower risk of the new treatments cohort for PE (HR 0.72; 95% CI 0.56-0.91, p = 0.007) and 5-year mortality (HR 0.70, 95%CI 0.54-0.91, p = 0.009). When considering both clinical and procedural variables, complete revascularization (HR 0.46, 95%CI 0.27-0.80, p = 0.006) and the administration of prasugrel or ticagrelor (HR 0.72, 95%CI 0.52-0.99, p = 0.013) were independent predictors of PE as well as of 5-year mortality. Patients receiving prasugrel or ticagrelor or drug eluting stent were at lower risk of 1-year stent thrombosis (HR 0.50, 95%CI 0.28-0.90, p = 0.021).. In a real-word STEMI population the prognosis of patients has improved in the last decades, and this was associated to the use of new antithrombotic treatments and to the implementation of complete revascularization.

Topics: Drug-Eluting Stents; Humans; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Prognosis; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

This study aims to assess the association between body mass index (BMI) and platelet reactivity in STEMI patients treated with oral 3. Overall, 429 STEMI patients were enrolled in this study. Patients were divided into two groups according to BMI (BMI < 25 vs ≥ 25 kg/m. After propensity score matching, patients with BMI ≥ 25 had similar values of baseline platelet reactivity, while they had higher level of platelet reactivity at 1 and 2 h after the LD and higher rate of HRPT. Furthermore, multivariate analysis demonstrated that BMI ≥ 25 was an independent predictor of HTPR at 2 h (OR 2.01, p = .009). Conversely, starting from 4 h after the LD, platelet reactivity values and HRPT rates were comparable among the two study groups.. A BMI ≥ 25 kg/m

Topics: Blood Platelets; Body Mass Index; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

After treatment, high residual platelet reactivity (HRPR) is considered as an essential risk factor for recurrent ischemic events.. To evaluate the impact of fibrinogen on HRPR after implantation of emergency drug-eluting stents (DES) in patients treated with aspirin and clopidogrel or ticagrelor due to ST-elevation myocardial infarction (STEMI) and to explore the predictive values of HRPR and fibrinogen for adverse ischemic events at 12 months.. This single-center prospective observational study analyzed patients with STEMI who underwent primary percutaneous coronary intervention (PCI) with second-generation DES implantation from January 2017 to December 2018. Platelet reactivity was measured by thromboelastography (TEG) at 60-72 h after primary PCI. HRPR was defined as the adenosine diphosphate-induced maximum amplitude (MA. A total of 919 patients were analyzed, of which 512 (55.8%) received aspirin and clopidogrel and 406 (44.2%) received aspirin and ticagrelor. Elevated fibrinogen levels were associated with an increased prevalence of HRPR (P < 0.001). High fibrinogen (quartile IV, ≥ 410 mg/dL) was an independent risk factor for HRPR after multivariate regression (odds ratio 6.556, 95% confidence interval [CI]: 3.200-13.431, P < 0.001). When analyzed by Kaplan-Meier survival curves, the combination of high fibrinogen and HRPR was strongly predictive for ischemic major adverse cardiac events at 12 months compared to the group without HRPR and with low fibrinogen (hazard ratio 9.681, 95% CI: 4.467-20.98, log-rank P < 0.001). Similar results were confirmed in subgroups according to different dual antiplatelet therapies.. A combination of high fibrinogen and HRPR may identify recurrent adverse ischemic events over 12 months. Ticagrelor exhibited more potent platelet inhibition and a better prognosis than clopidogrel.

Topics: Adenosine; Aspirin; Clopidogrel; Fibrinogen; Humans; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Ticagrelor; Ticlopidine; Treatment Outcome

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

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

This study aimed to define the association between altitude and ticagrelor-associated dyspnea in patients with acute coronary syndrome (ACS).. We studied consecutive patients with de novo ACS who were admitted to two centers at a low altitude (18 and 25 m, n = 65) and two centers at a high altitude (1313 and 1041 m, n = 136). We managed them with ticagrelor between May 2017 and September 2017. Patients with ACS underwent an interventional procedure within <90 minutes in those with ST elevation and within <3 hours in those without ST elevation. We recorded the incidence of dyspnea in patients with ACS receiving ticagrelor therapy.. The mean age was 59.5 ± 10 years, and the mean ejection fraction was 43% ± 18%. A total of 110 (56.7%) patients had ST elevation and 84 (43.3%) did not. There were no significant differences in cardiac risk factors, concurrent medications, or procedural variables between the two groups. Dyspnea developed during hospitalization in 53 (38%) patients from high-altitude centers and in 13 (20%) patients from low-altitude centers (66 patients represented 32% of the total ACS cohort).. Dyspnea is a common multifactorial symptom in patients following development of ACS. Ticagrelor-induced dyspnea appears to be associated with altitude.

Topics: Acute Coronary Syndrome; Aged; Altitude; Dyspnea; Humans; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

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

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

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

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

Bleeding among populations undergoing percutaneous coronary intervention or coronary artery bypass grafting and among conservatively managed patients with acute coronary syndrome exposed to different dual antiplatelet therapy and triple therapy (i.e. dual antiplatelet therapy plus an anticoagulant) has not been previously quantified.. The objectives were to estimate hazard ratios for bleeding for different antiplatelet and triple therapy regimens, estimate resources and the associated costs of treating bleeding events, and to extend existing economic models of the cost-effectiveness of dual antiplatelet therapy.. The study was designed as three retrospective population-based cohort studies emulating target randomised controlled trials.. The study was set in primary and secondary care in England from 2010 to 2017.. Participants were patients aged ≥ 18 years undergoing coronary artery bypass grafting or emergency percutaneous coronary intervention (for acute coronary syndrome), or conservatively managed patients with acute coronary syndrome.. Data were sourced from linked Clinical Practice Research Datalink and Hospital Episode Statistics.. Coronary artery bypass grafting and conservatively managed acute coronary syndrome: aspirin (reference) compared with aspirin and clopidogrel. Percutaneous coronary intervention: aspirin and clopidogrel (reference) compared with aspirin and prasugrel (ST elevation myocardial infarction only) or aspirin and ticagrelor.. Primary outcome: any bleeding events up to 12 months after the index event. Secondary outcomes: major or minor bleeding, all-cause and cardiovascular mortality, mortality from bleeding, myocardial infarction, stroke, additional coronary intervention and major adverse cardiovascular events.. The incidence of any bleeding was 5% among coronary artery bypass graft patients, 10% among conservatively managed acute coronary syndrome patients and 9% among emergency percutaneous coronary intervention patients, compared with 18% among patients prescribed triple therapy. Among coronary artery bypass grafting and conservatively managed acute coronary syndrome patients, dual antiplatelet therapy, compared with aspirin, increased the hazards of any bleeding (coronary artery bypass grafting: hazard ratio 1.43, 95% confidence interval 1.21 to 1.69; conservatively-managed acute coronary syndrome: hazard ratio 1.72, 95% confidence interval 1.15 to 2.57) and major adverse cardiovascular events (coronary artery bypass grafting: hazard ratio 2.06, 95% confidence interval 1.23 to 3.46; conservatively-managed acute coronary syndrome: hazard ratio 1.57, 95% confidence interval 1.38 to 1.78). Among emergency percutaneous coronary intervention patients, dual antiplatelet therapy with ticagrelor, compared with dual antiplatelet therapy with clopidogrel, increased the hazard of any bleeding (hazard ratio 1.47, 95% confidence interval 1.19 to 1.82), but did not reduce the incidence of major adverse cardiovascular events (hazard ratio 1.06, 95% confidence interval 0.89 to 1.27). Among ST elevation myocardial infarction percutaneous coronary intervention patients, dual antiplatelet therapy with prasugrel, compared with dual antiplatelet therapy with clopidogrel, increased the hazard of any bleeding (hazard ratio 1.48, 95% confidence interval 1.02 to 2.12), but did not reduce the incidence of major adverse cardiovascular events (hazard ratio 1.10, 95% confidence interval 0.80 to 1.51). Health-care costs in the first year did not differ between dual antiplatelet therapy with clopidogrel and aspirin monotherapy among either coronary artery bypass grafting patients (mean difference £94, 95% confidence interval -£155 to £763) or conservatively managed acute coronary syndrome patients (mean difference £610, 95% confidence interval -£626 to £1516), but among emergency percutaneous coronary intervention patients were higher for those receiving dual antiplatelet therapy with ticagrelor than for those receiving dual antiplatelet therapy with clopidogrel, although for only patients on concurrent proton pump inhibitors (mean difference £1145, 95% confidence interval £269 to £2195).. This study suggests that more potent dual antiplatelet therapy may increase the risk of bleeding without reducing the incidence of major adverse cardiovascular events. These results should be carefully considered by clinicians and decision-makers alongside randomised controlled trial evidence when making recommendations about dual antiplatelet therapy.. The estimates for bleeding and major adverse cardiovascular events may be biased from unmeasured confounding and the exclusion of an eligible subgroup of patients who could not be assigned an intervention. Because of these limitations, a formal cost-effectiveness analysis could not be conducted.. Future work should explore the feasibility of using other UK data sets of routinely collected data, less susceptible to bias, to estimate the benefit and harm of antiplatelet interventions.. This trial is registered as ISRCTN76607611.. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in. People who have a heart attack are treated with a stent to open up the blocked artery that caused the heart attack, with surgery to bypass the blocked artery or with medication only. Whatever the treatment, they are prescribed one or more antiplatelet drugs, either aspirin only or aspirin and an additional antiplatelet (clopidogrel, prasugrel or ticagrelor), for 12 months after the heart attack. Antiplatelets are given to prevent another heart attack, but increase the risk of bleeding. We used a large general practice database and a database describing patients’ attendances and admissions to hospital to determine how many people bleed with different antiplatelet combinations. We found that, overall, up to 1 in 10 people taking antiplatelets (rising to 2 in 10 if also taking an anticoagulant such as warfarin or dabigatran) reported a bleed. Among patients treated with surgery or medication only, we compared aspirin only (which is a less potent therapy) with aspirin and clopidogrel (a more potent therapy). Among patients treated with stents, we compared aspirin and clopidogrel (less potent therapy) with aspirin and prasugrel or ticagrelor (more potent therapy). In all three populations, the more potent therapy increased the risk of bleeding by about one and a half times, but this was not offset by a reduced risk of having a subsequent heart attack. This may be explained by low adherence to the medication: between one-third and almost half of all patients did not adhere to their regimen, and non-adherence was generally higher among patients taking a more potent therapy. It may also be explained by bias inherent in the study, for example if the groups prescribed different antiplatelet regimens had different risks of having another heart attack. Nevertheless, the results show that doctors should be cautious about prescribing more potent antiplatelet therapy because it may increase serious bleeds without necessarily reducing the number of heart attacks.

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Cohort Studies; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Retrospective Studies; ST Elevation Myocardial Infarction; Ticagrelor

We investigated whether combination of glenzocimab, a GPVI inhibitor, with aspirin and ticagrelor provides additional antithrombotic effects, as GPVI has a critical role in atherothrombosis but minimal involvement in hemostasis.. We investigated the effects of glenzocimab (monoclonal antibody Fab fragment) using blood from healthy donors and patients with acute coronary syndrome treated with aspirin and ticagrelor. Platelets were stimulated with multiple agonists, including atherosclerotic plaque, from patients undergoing carotid endarterectomy.. Aspirin and ticagrelor partially inhibited atherosclerotic plaque-induced platelet aggregation by 48% compared with control (34 ± 3 vs 65 ± 4 U; P < .001). Plaque-induced platelet aggregation, adhesion, secretion, and activation were critically dependent on GPVI activation. Glenzocimab alone reduced plaque-induced aggregation by 75% compared with control (16 ± 4 vs 65 ± 4 U; P < .001) and by >95% when combined with aspirin and ticagrelor (3 ± 1 vs 65 ± 4 U; P < .001). Glenzocimab reduced platelet aggregation, adhesion, and thrombin generation when added to blood of aspirin- and ticagrelor-treated patients with acute coronary syndrome. Glenzocimab shared several antithrombotic effects with the GPIIb/IIIa inhibitor eptifibatide with less effect on general hemostasis assessed by rotational thromboelastometry. In a murine intravital model of ST-elevation myocardial infarction, genetic depletion of GPVI reduced microvascular thrombosis.. Addition of glenzocimab to aspirin and ticagrelor enhances platelet inhibition via multiple mechanisms of atherothrombosis. Compared with a GPIIb/IIIa inhibitor, glenzocimab shares multiple antithrombotic effects, with less inhibition of mechanisms involved in general hemostasis.

Topics: Acute Coronary Syndrome; Animals; Aspirin; Fibrinolytic Agents; Humans; Mice; Plaque, Atherosclerotic; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; ST Elevation Myocardial Infarction; Thrombosis; Ticagrelor

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

Sex-based outcome differences for women with ST-segment-elevation myocardial infarction (STEMI) have not been adequately addressed, and the role played by differences in prescription of potent P2Y. Data from British Cardiovascular Intervention Society national percutaneous coronary intervention database were analyzed, and 168 818 STEMI patients treated with primary percutaneous coronary intervention from 2010 to 2020 were included.. Among the included women (43 131; 25.54%) and men (125 687; 74.45%), P-P2Y. Women were less likely to be prescribed prasugrel or ticagrelor, were less likely to have radial access, and had a higher mortality when being treated for STEMI. Improving rates of P-P2Y

Topics: Clopidogrel; Female; Humans; Male; Prasugrel Hydrochloride; Registries; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Choosing optimal P2Y

Topics: Aged; Clopidogrel; Female; Frailty; Humans; Male; Medicare; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Retrospective Studies; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome; United States

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

Vomiting is associated with lower levels of ticagrelor concentration and higher platelet reactivity in the early hours of ST-elevation myocardial infarction. These results support reloading with a ticagrelor loading dose and/or treatment with intravenous platelet inhibitors when patients vomit.

Topics: Blood Platelets; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome; Vomiting

Combination therapy with platelet inhibitors and acid-suppressive agents is recommended for patients with acute ST-segment elevation myocardial infarction (STEMI) who underwent percutaneous coronary intervention (PCI), but there remains a paucity of data to evaluate both the efficacy and safety of these combinations. In this prospective study, a total of 170 patients with acute STEMI who underwent PCI were divided into four groups: pantoprazole + ticagrelor, omeprazole + ticagrelor, ranitidine + ticagrelor, and ticagrelor only. The risk of PCI, antithrombotic efficacy, cardiac function, and main end points were evaluated and compared. No significant differences were found in infarction-related artery perfusion indexes (thrombolysis in myocardial infarction [TIMI], corrected TIMI frame count), the incidence of stent thrombosis after PCI, platelet indicators (platelet count, mean platelet volume, and platelet distribution width), platelet activation (P-selectin and glycoprotein IIb/IIIa levels), platelet aggregation (thrombelastography indicators, such as ADP% and MA

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

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

Ticagrelor is one of the main antiplatelet drugs used for prevention of coronary blood clots after interventional procedures in patients with acute coronary syndromes. It has previously been shown that gene variants of

Topics: Cytochrome P-450 CYP2C19; Cytochrome P450 Family 4; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Polymerase Chain Reaction; ST Elevation Myocardial Infarction; Ticagrelor

Ticagrelor is a first-line drug for the treatment of acute ST elevation myocardial infarction (STEMI). However, approximately 20% STEMI patients taking ticagrelor exhibited a delayed response and the mechanism was still unclear.. To explore the mechanism of the poor response of ticagrelor in post-percutaneous coronary intervention (PCI) patients, we enrolled 65 high platelet reactivity (HPR) patients and 90 controls (normal platelet reactivity [NPR]). Pharmacokinetic assessment result showed that the plasma concentrations of ticagrelor and its metabolism production, AR-C124910XX, were lower in HPR patients than controls. Further single nucloetide polymorphism (SNP) analysis identified that there is no difference in ATP binding cassette subfamily B member 1 (. Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with STEMI and support that modify gut microbiota is a potential therapeutic option for STEMI.. Our findings highlight that gut microbiota dysbiosis may be an important mechanism for the ticagrelor of HPR in patients with ST elevation myocardial infarction (STEMI) and support that modify gut microbiota is a potential therapeutic option for STEMI.. NSFC 82170297 and 82070300 from the National Natural Science Foundation of China.

Topics: Animals; Dysbiosis; Gastrointestinal Microbiome; Humans; Mice; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

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

Aim We hypothesised that pre-hospital ticagrelor loading would result in a higher proportion of STEMI patients presenting with pre percutaneous coronary intervention TIMI flow grade (ppTFG) 3 than had previously been reported in the clopidogrel era. Methods Retrospective observational analysis of all STEMI patients attending our centre from 01/01/2016 to 31/12/2019. Patients presenting with STEMI were required to have received pre-hospital load-ing with 180 mg ticagrelor. The coronary angiography images were assessed for each patient to determine the ppTFG in the infarct related artery. Results 590 patients met the inclusion criteria. 125 patients (21.2%) presented with ppTFG 3 on pre-PCI angiography with the remaining 465 patients (78.8%) presenting with ppTFG ≤ 2. In-hospital mor-tality was comparable between the two groups (4% vs 5.6%, p=0.48). Conclusion In STEMI patients loaded with ticagrelor in the field, over one-fifth present with ppTFG 3 on angi-ography pre-PCI. This data is comparable to data from the clopidogrel era.

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

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

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

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-hospital cardiac arrest (IHCA) is one of the most deleterious complications of ST-segment elevation myocardial infarction (STEMI).. We systematically analyzed the clinical characteristics of STEMI patients with IHCA, as well as predictors and treatments associated with risk of IHCA, using a nationwide database.. In the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project (2014-2019), we stratified patients presenting with STEMI within 24 hours after symptom onset according to IHCA or no IHCA during the index hospitalization. We analyzed patients' clinical characteristics, mortality, and independent correlates of IHCA.. Of 40,670 STEMI patients, 2.2% (95% CI: 2.1%-2.4%) experienced IHCA. Among IHCA patients, the in-hospital mortality was 53.0% (95% CI: 49.7%-56.3%). IHCA represents 55.0% (95% CI: 51.6%-58.4%) of inpatient deaths. Age ≥75 years, female, nonsmoker, prior diabetes mellitus, prior renal failure, out-of-hospital cardiac arrest, heart rate >100 beats/min, systolic blood pressure <90 mm Hg, and Killip IV were identified as predictors of IHCA. IHCA patients were less likely to receive β-blockers and ticagrelor during the first 24 hours after first medical contact and were less likely to undergo primary percutaneous coronary intervention. After adjustment, primary percutaneous coronary intervention (adjusted HR: 0.82; 95% CI: 0.71-0.95), β-blockers (adjusted HR: 0.63; 95% CI: 0.47-0.86), and ticagrelor (adjusted HR: 0.57; 95% CI: 0.42-0.76) were associated with a reduced risk of IHCA.. IHCA is rare in STEMI but is associated with high mortality. Multiple modifiable and unmodifiable factors are associated with its occurrence, suggesting that early intervention and rational drug treatment may improve its prognosis. (CCC Project- Acute Coronary Syndrome; NCT02306616).

Topics: Acute Coronary Syndrome; Adrenergic beta-Antagonists; Aged; Female; Hospitals; Humans; Out-of-Hospital Cardiac Arrest; Percutaneous Coronary Intervention; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Platelet glycoprotein IIb/IIIa inhibitors (GPIs) have been part of the adjuvant treatment of acute coronary syndrome for years. However, real-life data regarding the efficacy and safety of GPIs under the current indications are lacking in the setting of potent platelet inhibition. The objectives were to assess the efficacy and safety of abciximab versus tirofiban in patients with ST-elevation acute myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) and pretreated with ticagrelor, and to identify independent predictor factors of efficacy, bleeding and platelet drop. Three hundred sixty-two patients were divided by GPI administered. Clinical, laboratory, angiographic and outcome characteristics were compared. The primary objective was a composite efficacy endpoint (death from any cause, nonfatal myocardial infarction and nonfatal stroke) at 30 days. The secondary objectives were its individual components, safety (bleeding) and the impact on platelet count during hospital stay. The composite efficacy endpoint was similar in the abciximab and tirofiban groups (6.1% vs 7.3%;

Topics: Abciximab; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Ticagrelor; Tirofiban; Treatment Outcome

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

We aimed to evaluate the major adverse cardiac events and other clinical outcomes in ST-segment-elevation myocardial infarction (STEMI) cases treated with prasugrel versus ticagrelor after percutaneous intervention (PCI). The study was a prospective comparative study into which 560 patients diagnosed with STEMI, being suitable for PCI, and prescribed with either prasugrel (n = 232) or ticagrelor (n = 328) as oral antiplatelet therapy were included. Patients were followed up for a mean of 10.9 ± 4.7 months and 11.9 ± 4.9 months for prasugrel and ticagrelor groups, respectively. The major adverse cardiac events developed in similar rates between prasugrel and ticagrelor groups (7.3% versus 7.9%, respectively, p = 0.793). Even if mortality rate was higher in ticagrelor group, the difference did not reach statistically significance (3.4% vs. 6.7%, p=0.092). Among all study population, stent thrombosis and minor bleeding was recorded only in 7 (1.2%) and 12 (2.1%) patients without significant difference between prasugrel and ticagrelor groups. Twenty patients (8.6%) in prasugrel group and 47 patients (14.3%) in ticagrelor group discontinued treatment (p = 0.023). In ticagrelor group, 12 patients discontinued treatment due to dyspnea, but none in prasugrel group (p = 0.001). Prasugrel and ticagrelor have similar effects on major adverse cardiac events in patients with STEMI undergoing primary PCI, but prasugrel seems more tolerated and less discontinued than ticagrelor.

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

Among acute coronary syndromes (ACS), ST-segment elevation myocardial infarction (STEMI) has the most severe early clinical course. Recent randomized clinical trials have demonstrated that novel antithrombotic therapies improve in-hospital outcomes in STEMI patients. We aimed to describe the effectiveness and safety of P2Y12 receptor inhibitors in clinical practice in patients with STEMI based on data from contemporary European ACS registries.. Five registries from the PIRAEUS initiative (AAPCI/ADPAT, ALKK-PIC, AMIS Plus, Belgium STEMI, and EYESHOT) provided data for the assessment of P2Y12 receptor inhibitor-based dual antiplatelet therapy. Registries were heterogeneous in terms of setting, patient characteristics, and treatment selection. Matched pair analysis and propensity score matching were used to assess all-cause in-hospital death rates based on data from 25 250 patients (8577 patients on prasugrel, 5995 on ticagrelor, and 10 678 on clopidogrel). The odds ratio (OR) for the death of any cause when compared with clopidogrel was 0.72 [95% confidence interval (CI) 0.62-0.84, P < 0.001] in favour of the new P2Y12 receptor inhibitors (prasugrel and ticagrelor combined). In the comparison between prasugrel and ticagrelor, there were no relevant differences (OR 0.97, 95% CI 0.77-1.23; P = 0.81). Event rates of cardiovascular death and stroke were also substantially lower for the new P2Y12 receptor inhibitors. The differences between clopidogrel and prasugrel or ticagrelor on major bleeding were numerically in the same order as for death of any cause but were not statistically significant. No differences in ischaemic and bleeding outcomes were observed between prasugrel and ticagrelor.. This analysis suggests that the prasugrel or ticagrelor compared with clopidogrel have favourable outcomes in clinical practice while not being inferior in terms of safety.

Topics: Clopidogrel; Europe; Humans; Prasugrel Hydrochloride; Propensity Score; Purinergic P2Y Receptor Antagonists; Registries; ST Elevation Myocardial Infarction; Ticagrelor

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

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: Clopidogrel; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; ST Elevation Myocardial Infarction; Ticagrelor

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

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

Topics: Acute Coronary Syndrome; Angina, Unstable; Aspirin; Cardiac Rehabilitation; Clopidogrel; Combined Modality Therapy; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Secondary Prevention; ST Elevation Myocardial Infarction; Ticagrelor; United Kingdom

The aim of this study was to assess whether the effects of ticagrelor monotherapy after 3-month dual-antiplatelet therapy (DAPT) are consistent among patients presenting with ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction, and unstable angina treated with drug-eluting stents.. Ticagrelor monotherapy after short-term DAPT has not been investigated in patients with STEMI.. This was a pre-specified, stratified, subgroup analysis of the STEMI cohort from the TICO (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus Stent for Acute Coronary Syndrome) trial, which constituted 36% of the total population. The primary outcome was a composite of major bleeding and major adverse cardiac and cerebrovascular events (MACCE; death, myocardial infarction, stent thrombosis, stroke, or target vessel revascularization). The secondary outcomes were major bleeding and MACCE.. This pre-specified subgroup analysis revealed no heterogeneity in the effects of ticagrelor monotherapy after 3-month DAPT, compared with 12-month DAPT, for the primary outcome, major bleeding, and MACCE across clinical presentations including STEMI, though larger studies are needed to demonstrate these findings with adequate power. (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus Stent for Acute Coronary Syndrome [TICO Study]; NCT02494895).

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

Topics: Adenosine Monophosphate; Aged; Anxiety; Chest Pain; Coronary Angiography; Coronary Occlusion; Drug Substitution; Drug-Eluting Stents; Drug-Related Side Effects and Adverse Reactions; Dyspnea; Electrocardiography; Humans; Inferior Wall Myocardial Infarction; Male; Percutaneous Coronary Intervention; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome; Withholding Treatment

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

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

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

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

The rates of very elderly patients (≥85 years old) undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) are rapidly increasing. They are under-represented in clinical trials, and those who are included may not reflect the real-world population. We aim to review the clinical characteristics of very elderly patients undergoing PCI for ACS and identify factors associated with adverse outcomes.. All very elderly patients undergoing PCI for ACS in the Auckland region between January 2014 to December 2016 were included. Baseline clinical and procedural details were obtained, and the primary endpoint was all-cause mortality measured up to a maximum of 4 years. Secondary endpoints include recurrent myocardial infarction, unplanned revascularisation, stroke and major bleeding.. A total of 186 patients were included for analysis (mean age 87.6±2.8 years, 51.6% male). Indications for PCI were ST-elevation myocardial infarction (STEMI) in 74 (39.8%), non-ST elevation myocardial infarction (NSTEMI) in 97 (52.2%) and unstable angina in 15 patients (8.1%). Successful PCI was completed in 180 patients. At a maximal follow-up of 4 years (mean 23.4 mo), the rates of all-cause mortality and recurrent myocardial infarction were 22.0% and 14.0% respectively. The risk of mortality was increased by the presence of diabetes (44.8% vs 17.8%, HR=3.0, 95%CI: 1.6-5.9, p=0.001), STEMI (33.8% vs 13.5%, HR=3.1, 95%CI: 1.6-5.9, p=0.001), and reduced eGFR (every -10 mL/min/1.73m. Very elderly patients who undergo PCI for ACS have acceptable survival outcomes. STEMI, diabetes and impaired renal function were predictive of mortality in this elderly cohort.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Female; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

The newer adenosine diphosphate (ADP) receptor blockers ticagrelor and prasugrel are superior to clopidogrel in the long-term management of acute coronary syndrome (ACS). We evaluated the acute performance (prehospital loading) of these ADP receptor blockers in a primary percutaneous coronary intervention (PCI) for an ST-elevation myocardial infarction (STEMI).. In a retrospective, single-center registry study, data on all STEMI patients admitted for their first primary PCI between January 2007 and April 2020 were analyzed (n = 3218). The three ADP receptor blockers were mainly used during consecutive periods (clopidogrel 2007-2010, prasugrel 2011-2014, and ticagrelor 2014-2020), and were compared with risk factor-adjusted multivariate logistic regression for acute 3- and 7-day mortality and culprit artery flow before and after PCI.. Of the 3218 total patients, 47.6% (n = 1532) were treated with ticagrelor, 22.1% (n = 711) were treated with prasugrel, and 30.3% (n = 975) were treated with clopidogrel. The use of ticagrelor or prasugrel as opposed to clopidogrel was associated with better culprit artery flow before PCI (odds ratio [OR] 1.21 for moderate or good flow, 95% confidence interval [CI] 1.03-1.42, p = 0.022), as well as lower acute mortality (OR 0.66 for 3-day mortality, 95% CI 0.46-0.95, p = 0.025; and OR 0.71 for 7-day mortality, 95% CI 0.52-0.98, p = 0.039). The results in regard to acute mortality were highlighted among patients with short treatment delays (disappearing with longer treatment delays; p < 0.05 for interaction).. The newer ADP receptor blockers are associated with lower mortality and better culprit artery flow at presentation when compared with clopidogrel. There are no significant differences between the two newer drugs. As the drugs were mainly used during three consecutive periods, unmeasured confounding related to the development of cardiac care and changes in the population may contribute to the results.

Topics: Aged; Aged, 80 and over; Clopidogrel; Coronary Vessels; Female; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Registries; Retrospective Studies; Risk Factors; ST Elevation Myocardial Infarction; Survival Rate; Ticagrelor

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

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

Although ticagrelor exerts an antibacterial activity, its effect on infections in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) is unclear. We aimed to assess whether ticagrelor and clopidogrel affect infections in these patients during hospitalization.. A total of 2116 consecutive patients with STEMI undergoing PCI were divided into the ticagrelor (n = 388) and clopidogrel (n = 1728) groups. The primary outcome was infection onset. Secondary outcomes were in-hospital all-cause death and major adverse cardiovascular and cerebrovascular events (MACCE). Propensity score analyses were conducted to test the robustness of the results.. Infections developed in 327 (15.4%) patients. There was no significant difference in infection between both groups (ticagrelor vs. clopidogrel: 13.1% vs. 16.0%, p = 0.164). Patients in the ticagrelor group had lower rates of in-hospital all-cause death and MACCE than patients in the clopidogrel group. Multivariate logistic regression analysis determined that ticagrelor and clopidogrel had a similar preventive effect on infections during hospitalization (adjusted odds ratio [OR] = 1.20; 95% confidence interval [CI] = 0.80-1.78, p = 0.380). Compared to the patients treated with clopidogrel, patients treated with ticagrelor had a slightly lower risk of other outcomes, but no statistical difference. Propensity score analyses demonstrated similar results for infections and other outcomes.. Compared with clopidogrel treatment, ticagrelor treatment did not significantly alter the risk of infections during hospitalization among STEMI patients undergoing PCI, but was associated with a slightly lower risk of in-hospital all-cause death and MACCE.

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

To compare effectiveness and safety of clopidogrel, prasugrel, and ticagrelor among all-comers with ST-segment elevation myocardial infarction (STEMI) and extend the knowledge from randomized clinical trials.. All consecutive patients with STEMI admitted to Copenhagen University Hospital, Rigshospitalet, from 2009 to 2016 were identified via the Eastern Danish Heart Registry. By individual linkage to Danish nationwide registries, claimed drugs and end points were obtained. Patients alive a week post-discharge were included, stratified according to clopidogrel, prasugrel, or ticagrelor treatment, and followed for a year. The effectiveness end point (a composite of all-cause mortality, recurrent myocardial infarction, and ischemic stroke) and safety end point (a composite of bleedings leading to hospitalization) were assessed by multivariate Cox proportional-hazards models.. In total, 5123 patients were included (clopidogrel [1245], prasugrel [1902], ticagrelor [1976]) with ≥95% treatment persistency. Concomitant use of aspirin was ≥95%. Females accounted for 24% and elderly for 17%. Compared with clopidogrel, the effectiveness end point occurred less often for ticagrelor (HR 0.50, 95% CI 0.35-0.70) and prasugrel (HR 0.48, 95% CI 0.33-0.68) without differences in bleedings leading to hospitalization. No differences in comparative effectiveness or safety were found between prasugrel and ticagrelor. Sensitivity analyses with time-dependent drug exposure and the period 2011-2015 showed similar results.. Among all-comers with STEMI, ticagrelor and prasugrel were associated with reduced incidence of the composite end point of all-cause mortality, recurrent myocardial infarction, and ischemic stroke without an increase in bleedings leading to hospitalization compared with clopidogrel. No differences were found between prasugrel and ticagrelor.

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

To describe and evaluate outcomes in STEMI patients sustained on clopidogrel compared to those switched to ticagrelor following fibrinolysis.. World-wide, many STEMI patients cannot achieve timely PCI and therefore require fibrinolysis. Although comparable 30-day and 1-year safety was shown with clopidogrel or ticagrelor in the TREAT study, there is paucity of long-term outcomes in pharmacoinvasive treated STEMI.. We conducted an observational cohort study evaluating consecutive pharmacoinvasive STEMI patients treated in a network, comparing those switched to ticagrelor to those sustained on clopidogrel. The primary efficacy composite was one-year all-cause death, recurrent myocardial infarction, and stroke with major bleeding and intracranial hemorrhage (ICH) as the safety outcomes. Multivariable Cox regression model was used to examine the association between P2Y12 inhibitor and outcomes with inverse probability weighting.. Of 1426 pharmacoinvasive STEMI patients, 28% (n = 396) were converted to ticagrelor at a mean of 9.9 h after fibrinolysis with comparable GRACE Risk Scores (median; 158 vs 157, p0.352). The primary composite occurred in 3.5% of ticagrelor and 7.0% of clopidogrel treated patients (p0.014). Following adjustment, ticagrelor was associated with a 54% lower composite outcome (adjusted HR 0.46, 95% confidence interval 0.26-0.84). Major bleeding 6.3% vs 6.1% (NS) and ICH 0.0% vs 0.2% (NS) were similar.. In a prospective STEMI cohort, switching to ticagrelor compared with sustaining clopidogrel following fibrinolysis pharmacoinvasive reperfusion reduced recurrent ischemic events at 1-year with no differences in major bleeding or ICH. Aligned with randomized data, these findings provide support to switch pharmaco-invasively treated STEMI patients.

Topics: Clopidogrel; Drug Substitution; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Pregnancy-associated acute myocardial infarction is a rare condition usually occurring during the third trimester of pregnancy, and associated with three-to-four-fold higher mortality compared with rates among non-pregnant women of the same age. As in non-pregnant women, in cases of ST elevation myocardial infarction, the most effective treatment is primary percutaneous coronary intervention with stent implantation. Unfortunately, management of these patients could be challenging because little is known about the optimal medical strategy; the potential teratogenic effects of the third generation thienopyridines are not fully established too. In fact current guidelines do not provide enough recommendations about tailoring dual antiplatelet therapy prescription according to ischemic profile of the pregnant patients. Moreover, the bleeding risk class of cesarean delivery/hysterectomy is not stated in current consensus documents. We report the second pregnancy-associated acute myocardial infarction case successfully treated with ticagrelor before and after primary percutaneous coronary intervention with drug eluting stent implantation on left coronary artery, but also the first report on use of bridging antiplatelet therapy with tirofiban during temporary withdrawal of ticagrelor because of a C-section.

Topics: Adult; Cesarean Section; Female; Humans; Live Birth; Pregnancy; Pregnancy Complications, Cardiovascular; ST Elevation Myocardial Infarction; Ticagrelor; Tirofiban

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

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

To evaluate outcomes related to antiplatelet therapy in patients with ST-elevation myocardial infarction (STEMI) admitted to the San Gerardo Hospital in Monza, an extracorporeal membrane oxygenation (ECMO) reference center in the Monza-Brianza area.. This retrospective study enrolled patients with STEMI hospitalized between 2013 and 2017.. This study included 653 patients (mean age: 67.5 years, 71% male). Across the study period, ticagrelor use showed consistent increases, from 22% of patients during 2013 to 85% in 2017. Cardiac arrest prehospitalization occurred in 100 patients (15.3%), either at home (n = 85, 13.0%) or during transfer (n = 15, 2.3%); 46 patients underwent ECMO for refractory cardiac arrest. Rates of 90-day survival (hazard ratio [HR]: 2.4, 95% confidence interval [CI]: 1.3-4.4,. Changes in the treatment of high-risk patients with STEMI over time are in line with changes in treatment guidelines. In these patients, ticagrelor is associated with significantly improved 90-day mortality compared with clopidogrel.

Topics: Aged; Aged, 80 and over; Clopidogrel; Extracorporeal Membrane Oxygenation; Female; Humans; Italy; Male; Middle Aged; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Treatment Outcome

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

Topics: Follow-Up Studies; Humans; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor

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

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

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

Risk stratification with specific biomarkers is proposed for tailored P2Y12 inhibitor therapy in patients with STEMI.. This nationwide registry and quality improvement study is from November 1, 2014, to June 30, 2017. In total, 11,512 STEMI patients received aspirin and P2Y12 receptor inhibitor (clopidogrel or ticagrelor) and underwent PCIs in hospitals. Of the patients, 2992 were prescribed ticagrelor and 8520 clopidogrel. The primary effectiveness outcome was major adverse cardiovascular and cerebrovascular events (MACCE: cardiac death, myocardial infarction, stent thrombosis, in-hospital ischemic stroke). The primary safety outcome was in-hospital major bleeding.. MACCE incidence was lower in the ticagrelor group than in the clopidogrel group (0.8% versus 1.2%; P=0.046), but under different NT-proBNP levels, cumulative hazards of MACCE were without statistical significance. Bleeding rates were higher in the ticagrelor group than in the clopidogrel group (all bleeding: 9.9% versus 6.9%, P<0.001; major bleeding: 4.0% versus 2.7%, P<0.001). The higher cumulative hazard of bleeding could be identified in the Kaplan-Meier curves. In the multivariate analysis, ticagrelor increased bleeding events, compared with clopidogrel, at NT-proBNP >1800 ng/L patients (all bleeding: HR 1.46; 95%CI, 1.07-2.01; major bleeding: HR 1.68, 95%CI, 1.03-2.74), but a low effect was found in those with lower NT-proBNP level. Subgroup analyses show that ticagrelor increased major bleeding in patients with left ventricular ejection fraction (LVEF) <0.50 (HR 3.29; 95% CI 1.61-6.74) (interaction p=0.03).. We found that ticagrelor, compared with clopidogrel, increased bleeding complications in hospitalized patients with NT-proBNP>1800 ng/L, especially in patients with EF < 0.50.

Topics: Acute Coronary Syndrome; Clopidogrel; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Stroke Volume; Ticagrelor; Treatment Outcome; Ventricular Function, Left

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

Topics: Antigens, Human Platelet; Arginine; Aspirin; Autoantibodies; Combined Modality Therapy; Coronary Thrombosis; Drug Substitution; Drug Therapy, Combination; Eptifibatide; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Pipecolic Acids; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Platelet Transfusion; Purpura, Thrombocytopenic, Idiopathic; Shock, Cardiogenic; ST Elevation Myocardial Infarction; Stents; Sulfonamides; Thrombectomy; Thrombolytic Therapy; Thrombosis; Ticagrelor; Warfarin

Topics: Clopidogrel; Humans; Prasugrel Hydrochloride; ST Elevation Myocardial Infarction; Ticagrelor; Ticlopidine

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

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

In daily clinical practice, we encounter ST segment elevation myocardial infarction (STEMI) patients loaded with clopidogrel upon admission to primary angioplasty. These patients are loaded with ticagrelor, if there is no contraindication. This study aimed to compare the level of injury between STEMI patients who were first loaded with clopidogrel and the ones first loaded with ticagrelor. Although patients were switched from clopidogrel to ticagrelor at the first hour of angioplasty, antiplatelet action may still be lower than the others.. This study included STEMI patients with angina onset of ≤3 h and who had primary angioplasty to proximal segment of one coronary artery. All patients had total thrombotic occlusion at the proximal segment. Δtroponin level (6th-hour troponin-admission troponin) was calculated to compare the level of myocardial injury.. A total of 105 patients were included; 52 were loaded with ticagrelor and 53 with clopidogrel first and switched to ticagrelor. Baseline characteristics were similar in the two groups, except from type B2 lesions being more common in the ticagrelor-loaded group. Δtroponin levels were significantly higher in the clopidogrel-loaded group compared with the ticagrelor-loaded group (p=0.013). Major bleeding and in-hospital MACE rates were similar in both groups.. In STEMI patients, the degree of troponin rise was more prominent in clopidogrel-loaded patients, despite the switch to ticagrelor in the first hour of intervention. Clopidogrel is slow and modest, and variable platelet inhibition may continue to be a negative factor for protection from myocardial injury, even after switching to ticagrelor.

Topics: Angioplasty; Clopidogrel; Echocardiography; Electrocardiography; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Retrospective Studies; Severity of Illness Index; ST Elevation Myocardial Infarction; Ticagrelor; Troponin

The pharmacodynamics (PD) and pharmacokinetics (PK) study of ticagrelor loading dose (LD) in Chinese patients with acute coronary syndrome (ACS) without opioid administration has never been investigated. Therefore, the aim of this study was to evaluate the antiplatelet effects and the PK parameters of ticagrelor in Chinese patients with ACS without opioid administration.. A sample size of 30 eligible patients with ACS were enrolled in this study. Blood samples were obtained predose and 1, 2, 4, 8, and 12 h after 180 mg LD of ticagrelor. P2Y. In total, 15 patients were admitted to ST segment elevation myocardial infarction (STEMI) and non-ST segment elevation myocardial infarction (NSTEMI) groups, respectively. For patients with NSTEMI, PRU declined significantly during the first 4 h and maintained a relatively stable antiplatelet effect from 4 to 12 h after LD. A similar trend was found in the STEMI group without significant differences of PRU in each designed time compared with patients with NSTEMI (P > 0.05). T. For Chinese patients with ACS, at least 4 h was needed to achieve an adequate antiplatelet effect for ticagrelor LD. There were no differences in PK or PD between Chinese patients with STEMI and NSTEMI.. ChiCTR1800014764.

Topics: Analgesics, Opioid; China; Humans; Non-ST Elevated Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor

Topics: Humans; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome; Ventricular Remodeling

We evaluated the effects of atorvastatin and ticagrelor combination therapy on renal function and the levels of suppression of tumorigenicity 2 (ST2) and interleukin 33 (IL-33) in patients with ST-segment elevation myocardial infarction (STEMI).. Eighty-four STEMI patients who underwent emergency percutaneous coronary intervention at our hospital from January 2015 to March 2018 were retrospectively analyzed and divided into a control group (n = 44) and an observation group (n = 40). The control group was treated with atorvastatin as routine STEMI treatment, whereas the observation group was concurrently administered ticagrelor.. After treatment, significantly better outcomes were observed in the control group than in the observation group in terms of clinical indices, including chest pain relief, enzyme levels, duration of reperfusion-associated arrhythmia, and depression of the ST segment. Both groups exhibited improvements in cardiac ultrasound indices, whereas the observation group showed lower left ventricular end-diastolic and end-systolic diameters and higher left ventricular ejection fractions than the control group.. Atorvastatin and ticagrelor combination therapy is clinically effective and safe for STEMI patients as it reduces the degree of myocardial infarction, protects the heart and renal functions, improves inflammation, and reduces adverse cardiac event incidences.

Topics: Atorvastatin; Humans; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Percutaneous Coronary Intervention; Retrospective Studies; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

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

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

This study sought to analyze the impact of the preprocedural thrombolysis in myocardial infarction (TIMI) flow on clinical outcome in patients with ST-elevation myocardial infarction (STEMI).. Previous studies have shown that the TIMI flow 0/1 prior to primary percutaneous coronary intervention (PCI) is associated with a poor clinical outcome. However, it is unclear whether the same is true in patients with ongoing STEMI of less than 6 hr duration, rapid reperfusion, and modern guideline-adherent therapy.. The ATLANTIC study compared prehospital versus inhospital treatment with ticagrelor in patients with acute STEMI. For this analysis, patients were divided into three groups according to the preprocedural TIMI flow grade of the infarct vessel: TIMI 0/1, TIMI 2, and TIMI 3.. From a total of 1,680 patients, 1,113 had TIMI 0/1, 279 TIMI 2, and 288 TIMI 3 flow before primary PCI. At 30 days, the composite ischemic endpoint (5.5, 2.9, and 2.1%, p < .05) and all-cause death (3.0, 1.4, and 2.1%, p = .30) were highest in patients with TIMI flow 0/1. After adjustment, preprocedural TIMI flow <3 (versus 3) was not an independent predictor of major adverse ischemic events within 30 days (odds ratio 1.89, 95% confidence interval 0.74-4.85). However, definite stent thrombosis occurred only in patients with initial TIMI flow 0/1 (1.0%). Among these patients, those with prehospital administration of ticagrelor were less often affected (0.3% vs. 1.3%, p < .05).. In this post-hoc analysis, preprocedural TIMI flow was not independently associated with a higher rate of adverse ischemic events.

Topics: Aged; Cause of Death; Coronary Circulation; Coronary Thrombosis; Drug Administration Schedule; Europe; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Treatment Outcome

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

Robust comparisons between oral P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) in ST-elevation myocardial infarction (STEMI) patients who undergo primary percutaneous coronary intervention are lacking. We sought to evaluate outcomes on the basis of P2Y12 inhibitor therapy in patients from the Thrombectomy With PCI Versus PCI Alone in Patients With STEMI Undergoing Primary PCI (TOTAL) trial.. We grouped 9932 patients according to P2Y12 inhibitor at hospital discharge: clopidogrel (n = 6500; 65.5%), prasugrel (n = 1244; 12.5%), or ticagrelor (n = 2188; 22.0%). The primary composite end point of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association class IV heart failure was examined at 1 year. Secondary efficacy and safety end points were also assessed. Cox proportional hazard ratios were determined and adjusted for confounders via propensity scoring.. Baseline characteristics differing between the 3 groups were mainly age 75 years or older, diabetes, and previous stroke. After adjustment, ticagrelor use was associated with a lower rate of the primary composite outcome compared with clopidogrel (adjusted hazard ratio [aHR], 0.72; 95% confidence interval [CI], 0.57-0.91; P < 0.02) and prasugrel (aHR, 0.65; 95% CI, 0.48-0.89; P = 0.02). Prasugrel use was not associated with a lower rate of the primary outcome compared with clopidogrel (aHR, 1.09; 95% CI, 0.86-1.39; P > 0.99). Neither prasugrel nor ticagrelor were associated with increased risk of stroke compared with clopidogrel. Compared with clopidogrel, ticagrelor was associated with significantly lower rates of major bleeding.. In this observational analysis of STEMI patients who underwent primary percutaneous coronary intervention, ticagrelor was associated with improved outcomes compared with clopidogrel and prasugrel. An appropriately powered randomized trial is needed to confirm these findings.

Topics: Aged; Clopidogrel; Combined Modality Therapy; Female; Humans; Male; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Ticagrelor is a drug widely used in patients with acute coronary syndromes (ACS) that specifically increases the plasma level of adenosine, which is likely to cause atrial fibrillation (AF). Therefore, in this study we aimed to investigate the electrocardiographic and echocardiographic predictors of AF development after P2Y12 receptor antagonists in ACS patients.. This cross-sectional study included 831 patients with ACS (486 [58.5%] with ST elevated myocardial infarction [STEMI] and 345 [41.5%] with non-ST elevated myocardial infarction [NSTEMI]). Patients were divided into ticagrelor (n = 410) and clopidogrel (n = 421) groups. P wave properties including P wave dispersion and atrial electromechanical conduction properties were measured as AF predictors with surface ECG and tissue Doppler imaging.. Baseline characteristics such as age, sex, heart rate, blood pressure, and laboratory parameters were almost the same in the ticagrelor and clopidogrel groups. The statistical analysis showed no significant difference in P wave dispersion (PWD) between ticagrelor and clopidogrel groups (40.98 ± 12 ms versus 40.06 ± 12 ms, P = 0.304). Subgroups analysis according to ACS types also showed no significant difference in PWD (NSTEMI: 41.16 ± 13.8 ms versus 40.76 ± 13.55 ms, P = 0.799; STEMI: 40.9 ± 12.62 ms versus 39.19 ± 11.18 ms, P = 0.132). In addition, we did not find significant difference in atrial electromechanical delay (EMD) with tissue Doppler imaging (interatrial EMD 24.11 ± 3.06 ms versus 24.46 ± 3.23 ms, P = 0.279).. In conclusion, we did not find any difference in detailed electrocardiographic and echocardiographic parameters as AF predictors between ticagrelor and clopidogrel groups in patients with ACS

Topics: Acute Coronary Syndrome; Atrial Fibrillation; Clopidogrel; Cross-Sectional Studies; Echocardiography, Doppler; Electrocardiography; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor

Ticagrelor as a P2Y12 receptor antagonist is recommended in patients with acute coronary syndrome without a primary cardiosurgical therapy. Severe relevant side effects, especially anaphylactic reactions, have not yet been described in the current literature.. We describe the first documented case in the current literature with a severe anaphylaxis after ticagrelor in a 76-year-old male patient with ST-elevation myocardial infarction. The diagnosis seems to be objectivated by the observed time-related life-threatening event after repetitive administration of ticagrelor and the rapid stabilization after adequate anaphylactic treatment.. This case should raise the awareness that a supposedly safe drug can still cause an anaphylactic shock.. Die Kasuistik beschreibt den ersten dokumentierten Fall mit einer klinisch gesicherten schweren Anaphylaxie nach Ticagrelor bei einem 76-jährigen männlichen Patienten mit ST-Hebungs-Myokardinfarkt (STEMI).

Topics: Adenosine; Aged; Humans; Male; Platelet Aggregation Inhibitors; Shock; ST Elevation Myocardial Infarction; Ticagrelor

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Therapy, Combination; Female; Humans; Kaplan-Meier Estimate; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Retrospective Studies; ST Elevation Myocardial Infarction; Staphylococcal Infections; Ticagrelor; Time Factors; Treatment Outcome

The aim of this observational study was to determine the benefits of the novel, orally delivered P2Y. The goal of ST-elevation myocardial infarction (STEMI) treatment is timely reperfusion. The P2Y. The 328 eligible patients with STEMI consecutively referred for pPCI were divided into three groups depending on the interval of "P2Y. This observational study suggests that the angiographic benefit of P2Y

Topics: Administration, Oral; Aged; Blood Platelets; Coronary Angiography; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Time-to-Treatment; Treatment Outcome

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

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

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

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

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

The aim of this study is to investigate the impact of ticagrelor as compared to clopidogrel based dual antiplatelet therapy (DAPT) during post-discharge management on the incidence of left ventricular (LV) thrombus in patients with first acute anterior ST elevation myocardial infarction (STEMI).. 641 patients who met the inclusion criteria were divided into two groups based on the receipt of either ticagrelor or clopidogrel based DAPT.. Left ventricular thrombus was detected in 73 (11.4%) patients at the first month echocardiographic examination. Ticagrelor based DAPT was associated with significantly less incidence of LV thrombus when compared to clopidogrel [20 (7.4%) vs 53 (14.0%) OR: 0.50 (0.29-0.86)]. Penalized maximum likelihood estimation (PMLE) logistic regression analyses were performed to fourteen candidate variables for identifying the independent predictors of LV thrombus, ticagrelor (compared with clopidogrel) [OR: 0.53 (0.28-0.96), p = 0.039], body mass index (BMI) [OR: 0.58 (0.44-0.77), p < 0.001], KILLIP class (I vs II-IV) [OR: 0.35 (0.14-0.83), p = 0.017], age [OR: 1.22 (1.08-1.40), p < 0.001], poor postprocedural myocardial blush grade (MBG) [OR: 3.35 (1.32-8.15), p = 0.012] and LVEF predischarge [OR: 0.79 (0.72-0.86), p < 0.001] were found to be associated with LV thrombus.. Our study demonstrated that the incidence of LV trombus was significantly lower with ticagrelor than clopidogrel-based DAPT during postdischarge treatment for anterior STEMI patients.

Topics: Aged; Anterior Wall Myocardial Infarction; Aspirin; Clopidogrel; Coronary Angiography; Dose-Response Relationship, Drug; Dual Anti-Platelet Therapy; Echocardiography; Female; Follow-Up Studies; Heart Diseases; Heart Ventricles; Humans; Incidence; Male; Middle Aged; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Retrospective Studies; ST Elevation Myocardial Infarction; Thrombosis; Ticagrelor; Treatment Outcome; Turkey

Topics: Clopidogrel; Coronary Artery Disease; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Stents; Thrombosis; Ticagrelor

Topics: Aged; Cardiac Surgical Procedures; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Humans; Male; Platelet Aggregation; Postoperative Hemorrhage; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor

Topics: Clopidogrel; Fibrinolysis; Humans; ST Elevation Myocardial Infarction; Thrombolytic Therapy; Ticagrelor

Topics: Abciximab; Adult; Aspirin; Coronary Angiography; Coronary Thrombosis; Coronary Vessels; Female; Humans; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Ticagrelor; Tomography, Optical Coherence

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

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

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

Current clinical guidelines of acute coronary syndromes (ACS) recommend the use of potent antiplatelet therapy, prasugrel or ticagrelor, because both drugs consistently reduce cardiovascular events.. The aim of this study was to examine temporal changes in the use of optimal antiplatelet therapy in patients with ACS.. A total of 1717 consecutive patients admitted for ACS in 3 tertiary hospitals from February 2014 to December 2015 were enrolled. We divided these 23 months into 4 semesters: period I (0-5 months), period II (6-11 months), period III (12-17 months), and period IV (17-23 months). Demographic, clinical, and treatment data were collected both at admission and at discharge.. Treatment with clopidogrel remained constant throughout the periods (52%, 50%, 44%, and 50% for periods I, II, III, and IV, respectively), whereas a progressive increase in ticagrelor treatment was observed (15%, 25%, 26%, and 28%; P = .001). Indeed, new P2Y12 agents showed an increase from 47% at the first semester to 65% in patients with ST-segment elevation myocardial infarction (STEMI), and in patients younger than 75 years from 36% to 53%. However, for patients older than 75 years, diabetic, and patients with end-stage kidney disease, clopidogrel was the second most commonly used antiplatelet agent.. In this real-life registry of patients with ACS, we observed there is still a high rate of use of clopidogrel, despite guidelines recommendations, and our analyses also showed a trend toward the use of ticagrelor. Patients who received new antiplatelet agents were patients with STEMI, younger than 75 years, and with less comorbidities. However, the use of ticagrelor and prasugrel remains low, highlighting a therapeutic inertia with considerable gap between evidence-based clinical guidelines and daily clinical practice.

Topics: Acute Coronary Syndrome; Adenosine; Age Factors; Aged; Clopidogrel; Female; Hospitalization; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Practice Patterns, Physicians'; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Registries; ST Elevation Myocardial Infarction; Ticagrelor; Ticlopidine

According to guidelines, it is recommended to give P2Y

Topics: Adenosine; Adult; Aged; Clopidogrel; Humans; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Poland; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Registries; ST Elevation Myocardial Infarction; Ticagrelor; Ticlopidine

Patients with ST-segment elevation myocardial infarction (STEMI) and consecutive cardiogenic shock (CS) represent a challenge in clinical practice. Only few 'real-world' data on therapeutic management and outcome exist.. The present analysis focuses on changes of clinical management of STEMI-patients with CS and analyzes predictors of outcome using the Bremen-STEMI registry.. Out of 7865 patients with STEMI, 981 patients (13%) presented with CS. Most CS patients (88%) underwent an early percutaneous intervention (PCI). Intraaortic balloon pumps (IABP) were less implanted since 2013 (p < 0.001), the rate of drug-eluting stents and periprocedural prasugrel or ticagrelor therapy increased over the years. Overall in-hospital mortality of patients with CS was 37%, 1 year mortality was 50%. A significantly reduced 1-year mortality (2006-2009: 55%, 2010-2013: 50%; 2014-2015: 43%, p = 0.027) was observed. In a multivariate analysis significant predictors of an increased 1-year mortality were acute renal failure (OR 3.6; 95% CI 1.9-7.0), atrial fibrillation (OR 2.8; 95% CI 1.3-6.0), three-vessel disease (OR 2.5; 95% CI 1.3-4.7), age ≥ 75 years (OR 2.4, 95% CI 1.3-4.4) and anemia (OR 1.9; 95% CI 1.1-3.3). A successful performed PCI (OR 0.5, 95% CI 0.2-0.9) was associated with a significantly reduced 1-year mortality.. management of patients with CS changed with a steep decrease of IABP implantations. Mortality of patients with CS decreased over the last 10 years. Especially, performance of successful PCI was associated with a reduction of mortality, indicating the crucial role of early revascularization to improve prognosis in this high-risk cohort of STEMI-patients.

Topics: Adenosine; Aged; Chi-Square Distribution; Comorbidity; Drug-Eluting Stents; Female; Germany; Heart-Assist Devices; Hospital Mortality; Humans; Intra-Aortic Balloon Pumping; Logistic Models; Male; Middle Aged; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Prasugrel Hydrochloride; Registries; Risk Factors; Shock, Cardiogenic; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Treatment Outcome

Prasugrel and ticagrelor both reduce ischaemic endpoints in high-risk acute coronary syndromes, compared with clopidogrel. However, comparative outcomes of these two newer drugs in the context of primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) remains unclear. We sought to examine this question using the British Cardiovascular Interventional Society national database in patients undergoing primary PCI for STEMI.. Data from January 2007 to December 2014 were used to compare use of P2Y12 antiplatelet drugs in primary PCI in >89 000 patients. Statistical modelling, involving propensity matching, multivariate logistic regression (MLR) and proportional hazards modelling, was used to study the association of different antiplatelet drug use with all-cause mortality.. In our main MLR analysis, prasugrel was associated with significantly lower mortality than clopidogrel at both 30 days (OR 0.87, 95% CI 0.78 to 0.97, P=0.014) and 1 year (OR 0.89, 95% CI 0.82 to 0.97, P=0.011) post PCI. Ticagrelor was not associated with any significant differences in mortality compared with clopidogrel at either 30 days (OR 1.07, 95% CI 0.95 to 1.21, P=0.237) or 1 year (OR 1.058, 95% CI 0.96 to 1.16, P=0.247). Finally, ticagrelor was associated with significantly higher mortality than prasugrel at both time points (30 days OR 1.22, 95% CI 1.03 to 1.44, P=0.020; 1 year OR 1.19 95% CI 1.04 to 1.35, P=0.01).. In a cohort of over 89 000 patients undergoing primary PCI for STEMI in the UK, prasugrel is associated with a lower 30-day and 1-year mortality than clopidogrel and ticagrelor. Given that an adequately powered comparative randomised trial is unlikely to be performed, these data may have implications for routine care.

Topics: Aged; Clopidogrel; Coronary Restenosis; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Care; Prasugrel Hydrochloride; Retrospective Studies; ST Elevation Myocardial Infarction; Survival Rate; Ticagrelor; United Kingdom

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

Preload with clopidogrel, ticagrelor, or prasugrel in the setting of ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) is frequently applied. Limited data are available regarding the outcome impact of pretreatment with these drugs in the real world.. The outcome of 760 STEMI patients treated by primary PCI receiving clopidogrel, prasugrel, or ticagrelor (n = 269, 327, 164, respectively) was evaluated. Patients in the clopidogrel group were older, whereas those in the ticagrelor group had less hypertension but were more active smokers. Angiographic characteristics were comparable among the three groups. At 1 month, more events were observed in the clopidogrel group (11.1%) than in the ticagrelor and prasugrel groups (7.1 vs. 5.1%, P = 0.025), whereas the number of events in the ticagrelor and prasugrel groups did not differ. At 1 year, similar differences existed, mainly driven by a higher rate of death (19.5%, P = 0.008) or stent thrombosis (2 vs. 1.3% for ticagrelor, P = 0.132; vs. 0.3% for prasugrel, P = 0.07) in the clopidogrel group. In-hospital and 1-year bleeding rates were similar between groups.. In real-world practice, pretreatment with prasugrel or ticagrelor in ongoing STEMI treated by primary PCI seems to be a well tolerated alternative strategy compared with clopidogrel but provides superior benefit in terms of outcomes.

Topics: Aged; Belgium; Clopidogrel; Female; Hemorrhage; Humans; Male; Middle Aged; Multivariate Analysis; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Preoperative Care; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Stents; Survival Analysis; Thrombosis; Ticagrelor; Time Factors; Treatment Outcome

Few data exist on temporal evolution of antithrombotic agent use in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) in Italy. We sought to compare data from the most recent prospective, multicenter, nationwide registries conducted in Italy, namely EYESHOT and SCOPE.. EYESHOT enrolled 2585 consecutive ACS patients, both ST-segment elevation myocardial infarction (STEMI) and non-ST elevation ACS (NSTE-ACS), admitted to 203 Italian coronary care units over a 3-week period (2-22 Dec 2013 and 27 Jan-16 Feb 2014). Among patients enrolled in EYESHOT, 1755 (67.9%) underwent PCI (52.6% with STEMI and 47.4% with NSTE-ACS). In the SCOPE registry, a total of 1363 patients undergoing PCI were enrolled over 3 months (15 Feb-15 Apr 2016) in 39 Italian cath lab centers at medium to high PCI volume: 331 (24.3%) with a diagnosis of STEMI and 1032 (75.7%) with a diagnosis of NSTE-ACS.. Over 2 years, the use of clopidogrel in the cath lab significantly decreased (from 11% to 8% in STEMI; p=0.06 and from 9% to 5% in NSTE-ACS; p=0.0002), while the administration of ticagrelor dramatically increased (from 14% to 37%; p<0.0001 in STEMI and from 7% to 44%; p<0.0001 in NSTE-ACS). At discharge, a significant decrease in the use of clopidogrel (from 32% to 21% in STEMI; p=0.02, and from 47% to 24% in NSTE-ACS; p<0.0001) and a concomitant increase in the novel P2Y12 receptor inhibitor prescription occurred, particularly among NSTE-ACS patients (from 8% to 14% for prasugrel; p=0.002 and from 43% to 58% for ticagrelor; p=0.03).. From the present analysis on ACS patients undergoing PCI enrolled in EYESHOT and SCOPE registries, a significant increase in the use of novel P2Y12 receptor inhibitors was observed, both at the time of PCI and at discharge.

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Fibrinolytic Agents; Humans; Italy; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Registries; ST Elevation Myocardial Infarction; Ticagrelor; Ticlopidine

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

The effects of ticagrelor pretreatment in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI) is debated. This study investigated the effects of ticagrelor pretreatment on clinical outcomes in this patient group.. Patients with ST-segment-elevation myocardial infarction undergoing primary PCI were included from October 2010 to October 2014 in Sweden. Screening was done using the SWEDEHEART register (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies). A total of 7433 patients were included for analysis with 5438 patients receiving ticagrelor pretreatment and 1995 patients with ticagrelor given only in the catheterization laboratory. The primary end point of the study was 30-day event rates of a composite of all-cause mortality, myocardial infarction (MI), and stent thrombosis. Secondary end points were mortality, MI, or stent thrombosis alone and major in-hospital bleeding. Crude event rates showed no difference in 30-day composite end point (6.2% versus 6.5%;. Ticagrelor pretreatment versus ticagrelor given in the catheterization laboratory in patients with ST-segment-elevation myocardial infarction undergoing primary PCI did not improve the composite end point of all-cause mortality or MI or stent thrombosis or its individual components at 30 days.

Topics: Aged; Coronary Thrombosis; Drug Administration Schedule; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Recurrence; Registries; Risk Factors; ST Elevation Myocardial Infarction; Sweden; Ticagrelor; Time Factors; Treatment Outcome

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

This study aimed to explore the effects of ticagrelor (a P2Y12 receptor inhibitor) on interleukin (IL)-17 and myeloperoxidase (MPO) expression in coronary thrombus as well as on the coronary blood flow in ST-segment elevation myocardial infarction (STEMI) patients following percutaneous coronary intervention (PCI).. Forty STEMI patients who were admitted to the First Affiliated Hospital of Harbin Medical University between August 1, 2014 and December 30, 2014 were enrolled in this study according to a set inclusion criteria. They were randomized to ticagrelor and clopidogrel groups and treated with 180 mg ticagrelor and 600 mg clopidogrel before PCI, respectively. Intracoronary thrombus aspiration was performed by a physician during PCI. Immunohistochemistry and Western blot analysis were carried out to detect the expression of IL-17 and MPO in the thrombus. Corrected thrombolysis in myocardial infarction frame count (CTFC) was used to evaluate blood flow after PCI.. Immunohistochemistry results showed that the average positive staining area percentage of IL-17 and MPO in the clopidogrel group was significantly higher than that in the ticagrelor group. Western blot analysis also showed similar results for IL-17 (clopidogrel 0.71 ± 0.036, ticagrelor 0.50 ± 0.56) and MPO (clopidogrel 0.50 ± 0.040; ticagrelor 0.38 ± 0.06). CTFC was lower in the ticagrelor group than that in the clopidogrel group (P < 0.05).. Ticagrelor is more effective than clopidogrel in reducing inflammation thrombosis and improving postprocedural PCI blood flow in STEMI patients. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Topics: Adolescent; Adult; Aged; Clopidogrel; Coronary Circulation; Female; Humans; Interleukin-17; Middle Aged; Peroxidase; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Thrombosis; Ticagrelor; Young Adult

Topics: Chest Pain; Diagnosis, Differential; Hemorrhage; Humans; Lung Diseases; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; ST Elevation Myocardial Infarction; Ticagrelor; Tomography, X-Ray Computed

Prasugrel and ticagrelor are recommended over clopidogrel in patients with ST-elevation myocardial infarction (STEMI). In this registry analysis, we compared efficacy and safety of ticagrelor and prasugrel P2Y12 inhibition in patients with STEMI. We included 318 patients in this single-center analysis. Twelve-month follow-up was conducted during ambulatory care at our department. Patients were on dual antiplatelet therapy with aspirin and ticagrelor or prasugrel during the follow-up period. Prescription of prasugrel or ticagrelor, respectively, was according to the preference of the treating physician. Major adverse cardiac and cerebrovascular events (MACCE) [death, myocardial infarction (MI), stroke, and unplanned reintervention] and thrombolysis in myocardial infarction (TIMI) bleeding (major/minor) were registered during hospitalization and follow-up. TIMI bleeding events were more frequent in ticagrelor-treated patients [17 vs. 5 patients, hazard ratio (HR) 2.85, 95% confidence interval (CI) 1.2-6.6; log-rank P value = 0.01]. Prasugrel-treated patients were significantly younger (ticagrelor 63 ± 12 years vs. prasugrel 57 ± 10; P < 0.0001). Besides that, patients' characteristics were similar in both groups. Multivariate analysis revealed that ticagrelor medication was independently associated with bleeding risk after adjustment for age, percutaneous coronary intervention approach (femoral vs. radial), diabetes mellitus, and kidney function (HR 3.01; 95% CI 1.0-7.4; P = 0.043). In patients treated with ticagrelor, 35 MACCE were detected. There was no difference as compared to prasugrel-treated patients (24 events, HR 1.24, 95% CI 0.79-2.09; log-rank P value = 0.41). TIMI bleeding events were more frequent in ticagrelor-treated patients with STEMI during 12-month follow-up. There were no differences in MACCE between groups in this registry analysis.

Topics: Aged; Aspirin; Drug Therapy, Combination; Female; Germany; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Pilot Projects; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Recurrence; Registries; Risk Factors; ST Elevation Myocardial Infarction; Stroke; Ticagrelor; Time Factors; Treatment Outcome

Antithrombotic management of STEMI patients with apical dysfunction, but without demonstrable thrombus, is controversial. Triple antithrombotic therapy (TATT, defined as the addition of oral anticoagulation to dual antiplatelet therapy, or DAPT) may be associated with increased bleeding, while DAPT alone may not adequately protect against cardio-embolic events. We undertook a dual-center study of anterior STEMI patients treated with primary PCI (pPCI) from 2013 to 2015 and presenting presumed new apical dysfunction. The Centre hospitalier de l'Université de Montréal (CHUM) uses a strategy of selective TATT, whereas the Centre hospitalier universitaire de Sherbrooke (CHUS) has favored ticagrelor-based DAPT for all patients since 2013. The primary composite outcome consisted of death, MI, stroke, revascularization, and BARC 3 to 5 bleeding up to 4-months follow-up. We identified 177 cases (69 CHUM; 108 CHUS). Baseline characteristics were similar and procedural success was high (97%). There was no difference in post-procedure LVEF (39 ± 9% vs 37 ± 9%) or the extent of apical dysfunction. The primary composite outcome occurred in 27% with the selective TATT strategy compared to 19% with ticagrelor-DAPT (p = 0.342). Thus, this retrospective dual-center analysis does not support a strategy of conventional TATT over ticagrelor-based DAPT for patients with apical dysfunction following anterior STEMI treated with pPCI. A pragmatic randomized trial is needed to provide a definitive answer to this clinical conundrum.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Retrospective Studies; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome; Ventricular Dysfunction, Left; Young Adult

Ticagrelor is a state-of-the-art antiplatelet agent used for the treatment of patients with acute coronary syndromes (ACS). Unlike remaining oral P2Y12 receptor inhibitors ticagrelor does not require metabolic activation to exert its antiplatelet action. Still, ticagrelor is extensively metabolized by hepatic CYP3A enzymes, and AR-C124910XX is its only active metabolite. A post hoc analysis of patient-level (n = 117) pharmacokinetic data pooled from two prospective studies was performed to identify clinical characteristics affecting the degree of AR-C124910XX formation during the first six hours after 180 mg ticagrelor loading dose in the setting of ACS. Both linear and multiple regression analyses indicated that ACS patients presenting with ST-elevation myocardial infarction or suffering from diabetes mellitus are more likely to have decreased rate of ticagrelor metabolism during the acute phase of ACS. Administration of morphine during ACS was found to negatively influence transformation of ticagrelor into AR-C124910XX when assessed with linear regression analysis, but not with multiple regression analysis. On the other hand, smoking appears to increase the degree of ticagrelor transformation in ACS patients. Mechanisms underlying our findings and their clinical significance warrant further research.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clinical Trials as Topic; Female; Humans; Linear Models; Male; Middle Aged; Morphine; Platelet Aggregation Inhibitors; Prospective Studies; Regression Analysis; Smoking; ST Elevation Myocardial Infarction; Ticagrelor

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

Pretreatment with P2Y12 inhibitors before primary percutaneous coronary intervention (PPCI) can reduce the incidence of major adverse cardiovascular event (MACE) rate in ST-segment elevation myocardial infarction (STEMI) patients. We investigated differences in coronary reperfusion and clinical outcomes between prehospital administration of prasugrel vs ticagrelor in a historical cohort analysis.. We conducted a retrospective analysis of prospectively collected data of 533 STEMI patients, directly referred by the ambulance for PPCI, and pretreated with either prasugrel (2013-2014) or ticagrelor (2015-2016). The primary outcome measurement was coronary and myocardial reperfusion prior to and after intervention. Secondary outcome measurements included MACE and stent thrombosis (ST) at 30 days. The median time from first medical contact to balloon was 82 minutes. There was no significant difference in preprocedural and postprocedural coronary reperfusion (TIMI flow grade 3) and postprocedural ST-segment elevation resolution between the prasugrel and ticagrelor groups. No significant differences in MACE and ST rates were found between the groups. No fatal or intracranial bleedings were reported up to 30-day follow-up.. Prehospital administration of both prasugrel and ticagrelor in STEMI patients is safe, without differences in preprocedural and postprocedural reperfusion and short-term clinical outcomes.

Topics: Coronary Angiography; Electrocardiography; Emergency Medical Services; Female; Follow-Up Studies; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Preoperative Care; Retrospective Studies; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Time-to-Treatment; Treatment Outcome

Patients with acute coronary syndrome show an inflammatory response that is known to affect platelet aggregation. We aimed to clarify the relationship between the inflammation severity and the effect of antiplatelet therapy after percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).. This retrospective, single-center study included 203 patients with STEMI who underwent primary PCI and were stratified on the basis of the antiplatelet therapy on admission (clopidogrel vs ticagrelor). Inflammation levels were defined as low, intermediate, and high, based on the tertiles of the distribution of high-specificity C-reactive protein levels pre-PCI. Platelet aggregation function during hospitalization and follow-up was quantified as residual adenosine diphosphate-induced platelet reactivity on light transmittance aggregometry. Inflammation markers were measured on admission and at 1 year post-PCI.. At intermediate and high levels of inflammation, residual adenosine diphosphate-induced platelet aggregation was significantly higher among clopidogrel users than among ticagrelor users. In the clopidogrel group, statistically significant differences in platelet aggregation function were observed among the 3 levels of inflammation. At 1 year post-PCI, ticagrelor users had significantly lower levels of interleukin-1β and higher levels of interleukin-35 and transforming growth factor-β.. At different inflammation levels, ticagrelor provides more potent platelet inhibition than clopidogrel, suggesting that ticagrelor might exert a more stable antiplatelet effect at higher levels of systemic inflammation. Furthermore, ticagrelor is associated with reduced indices of inflammation on follow-up after PCI, suggesting that anti-inflammatory effects might play a role in the clinical benefit observed with antiplatelet therapy, which would provide an additional rationale for using ticagrelor in patients with STEMI undergoing primary PCI.

Topics: Biomarkers; C-Reactive Protein; Clopidogrel; Female; Humans; Interleukin-1beta; Interleukins; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Retrospective Studies; ST Elevation Myocardial Infarction; Ticagrelor; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

European guidelines recommend the use of ticagrelor versus clopidogrel in patients with ST elevation myocardial infarction (STEMI). This recommendation is based on inconclusive results and subanalyses from clinical trials. Few data are available on the effects of ticagrelor in a real-world population.. To compare the effects of ticagrelor and clopidogrel in a real-world STEMI population, we conducted a pre-post case-control study examining all patients with STEMI included in the Cardio-STEMI Sanremo registry between February 2011 and June 2013. Cases and controls were defined according to P2Y. Of the 416 patients enrolled in the Cardio-STEMI registry, 401 with a definite diagnosis of STEMI were included in this study. One hundred forty-two patients received ticagrelor and 259 received clopidogrel. Regarding clinical presentation and procedural data, those in the ticagrelor group had lower CRUSADE scores (23 [14-36] vs 27 [18-38]; p = 0.015] but a higher proportion of radial access (33% vs 14%; p < 0.001), percutaneous coronary intervention (PCI; 92% vs 81 %; p = 0.002) and primary PCI ≤ 12 h (82% vs 66%; p = 0.001). The patients in the ticagrelor group had a higher procedural success rate (100% vs. 96%; p = 0.044). There was no difference in Bleeding Academic Research Consortium bleeding and in unadjusted incidence of hospital major adverse cardiovascular events (MACE; cardiac death, myocardial infarction, or stroke) but there was a significant reduction in unadjusted cardiac hospital death in the ticagrelor group (0.7% vs 5.4%; p = 0.024). After correcting for propensity score, hospital death (p = 0.22) and hospital MACE (p = 0.96) did not differ in both groups. The unadjusted survival at 1 year after STEMI was higher in the ticagrelor group (97.8% vs 87.8%; p = 0.024), and this result was confirmed by propensity score analysis (hazard ratio = 0.29 [0.08-0.99]; p = 0.048).. In this real-word propensity score analysis, ticagrelor did not affect the risk of MACE during the hospital phase, or the incidence of hospital bleeding in patients with STEMI. However, in this mono-centric experience, ticagrelor resulted in improved 1-year survival, even after correction by propensity score.

Topics: Adenosine; Aged; Clopidogrel; Coronary Angiography; Dose-Response Relationship, Drug; Electrocardiography; Female; Follow-Up Studies; Hospital Mortality; Humans; Italy; Male; Middle Aged; Platelet Aggregation Inhibitors; Propensity Score; Purinergic P2Y Receptor Antagonists; Registries; Retrospective Studies; ST Elevation Myocardial Infarction; Survival Rate; Ticagrelor; Ticlopidine; Time Factors

The aim of this study was to assess the feasibility and clinical results following a pre-specified bioresorbable scaffold (Absorb BVS) implantation strategy in patients with ST-segment elevation myocardial infarction (STEMI).. Concerns were raised about the safety of Absorb because a non-negligible rate of thrombosis was reported within 30 days and at midterm follow-up after primary percutaneous coronary intervention.. This was a prospective, multicenter study of patients with STEMI (<75 years of age with symptom onset <12 h) undergoing primary percutaneous coronary intervention with Absorb following a dedicated implantation protocol. The primary endpoint was a device-oriented composite endpoint of cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization within 30 days.. During the study period, 505 patients with STEMI (16.9% of the overall STEMI population) were treated with the Absorb BVS. The mean age was 56.6 ± 9.4 years, and 487 patients (96.4%) were in Killip class I or II at admission. According to the study protocol, direct Absorb implantation was feasible in 47 patients (9.3%), whereas post-dilatation was performed in 468 cases (92.7%). Procedural success was attained in 94.8% of the cases. Dual antiplatelet therapy with ticagrelor or prasugrel was administered at discharge in 481 patients (95.1%). At 30-day follow-up, the hierarchical device-oriented composite endpoint rate was 0.6% (0.4% cardiac death, 0.2% target vessel myocardial infarction and ischemia-driven target lesion revascularization). One episode (0.2%) of probable scaffold thrombosis was reported.. A pre-specified Absorb implantation strategy in real-world patients with STEMI undergoing primary percutaneous coronary intervention was feasible and associated with a low 30-day device-oriented composite endpoint rate. Mid- and long-term follow-up is strongly needed to eventually confirm these early results. (Use of BVS in ST-Segment Elevation Myocardial Infarction [STEMI]: The BVS STEMI STRATEGY-IT Prospective Registry [STRATEGY-IT]; NCT02601781).

Topics: Absorbable Implants; Adenosine; Aged; Angioplasty, Balloon, Coronary; Aspirin; Coronary Thrombosis; Drug Therapy, Combination; Female; Humans; Italy; Male; Middle Aged; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Prosthesis Design; Recurrence; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Time Factors; Treatment Outcome

Data from available studies suggest that the presence of ST-elevation myocardial infarction (STEMI) may be associated with delayed and attenuated ticagrelor bioavailability and effect compared with non-ST-elevation myocardial infarction (NSTEMI).. In a single-center, prospective, observational trial 73 patients with myocardial infarction (STEMI n = 49, NSTEMI n = 24) underwent a pharmacokinetic and pharmacodynamic assessment after a 180 mg ticagrelor loading dose (LD). Ticagrelor and its active metabolite (AR-C124910XX) plasma concentrations were determined with liquid chromatography tandem mass spectrometry, and their antiplatelet effect was measured with the VASP assay and multiple electrode aggregometry.. During the first six hours after ticagrelor LD, STEMI patients had 38% and 34% lower plasma concentration of ticagrelor and AR-C124910XX, respectively, than NSTEMI (ticagrelor AUC(0-6): 2491 [344-5587] vs. 3991 [1406-9284] ng*h/mL; p = 0.038; AR-C124910XX AUC(0-6): 473 [0-924] vs. 712 [346-1616] ng*h/mL; p = 0.027). STEMI patients also required more time to achieve maximal concentration of ticagrelor (tmax: 4.0 [3.0-12.0] vs. 2.5 [2.0-6.0] h; p = 0.012). Impaired bioavailability of ticagrelor and AR-C124910XX seen in STEMI subjects was associated with diminished platelet inhibition in this group, which was most pronounced during the initial hours of treatment.. Plasma concentrations of ticagrelor and AR-C124910XX during the first hours after ticagrelor LD were one third lower in STEMI than in NSTEMI patients. This reduced and delayed ticagrelor bioavailability was associated with weaker antiplatelet effect in STEMI.. ClinicalTrials.gov identifier: NCT02602444 (November 09, 2015).

Topics: Adenosine; Aged; Biological Availability; Blood Platelets; Female; Humans; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Platelet Aggregation Inhibitors; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor

Dual antiplatelet therapy with aspirin and a P2Y12 receptor blocker has been proven to reduce subsequent cardiovascular events and in-stent thrombosis in patients undergoing percutaneous coronary intervention. Newer P2Y12 antagonists with faster onset and greater inhibition of platelet activity have improved cardiovascular outcomes but have created uncertainty with the appropriate dosing when switching between agents. Currently, there are no evidence-based guidelines to aid clinicians when switching between P2Y12 receptor blockers. Here we describe two patients that developed in-stent thrombosis when switching from ticagrelor to clopidogrel using a 300 mg clopidogrel loading dose. Both patients presented with ST elevation myocardial infarction and underwent stent placement but then developed in-stent thrombosis 48 hours after switching from ticagrelor to clopidogrel. These cases illustrate the severe consequences of suboptimal platelet inhibition and the need for prospective trials thoroughly powered to assess clinical outcomes in order to determine the most appropriate strategy when switching from ticagrelor to clopidogrel.

Topics: Adenosine; Blood Platelets; Clopidogrel; Drug Administration Schedule; Drug Dosage Calculations; Drug Substitution; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Stents; Thrombosis; Ticagrelor; Ticlopidine

The aim of this study was to evaluate access-site complications in patients with ST-segment elevation myocardial infarction treated with a transradial primary percutaneous coronary intervention relative to three different P2Y12 platelet inhibitors.. We enrolled 334 consecutive patients (76.9% men, age: 59.4±9.1 years) treated by one of the following: clopidogrel (n=118), prasugrel (n=102), and ticagrelor (n=114). The use of the IIb/IIIa inhibitor, abciximab, was left to the operators' discretion. The time needed to achieve patent hemostasis, compression time, and local complications were analyzed.. The baseline characteristics were similar in all three P2Y12 platelet inhibitor groups. Abciximab was used in 72 (21.6%) patients. Administration of abciximab was associated with a higher incidence of grade II and III hematomas (23.6 vs. 5.0%, P<0.0001, and 5.6 vs. 1.1%, P=0.041, respectively). Among different platelet P2Y12 receptor inhibitor groups, the incidences of hematomas grade II and III were similar in patients who did (P≥0.14) and did not (P≥0.31) receive abciximab. There were no grade IV or V hematomas in any of the groups. Patent hemostasis was achieved faster (24.5±13.4 vs. 43.5±30.0 min, P<0.0001) and compression time was shorter (113.2±53.6 vs. 217.8±115.5 min, P<0.0001) when abciximab was not used. Radial artery occlusion occurred in one (0.3%) patient.. After transradial primary percutaneous coronary intervention, early patent hemostasis and short artery compression times were associated with a higher incidence of local hematomas. The incidence of hematomas was dependent on the use of abciximab, but unrelated to the type of P2Y12 inhibitor used. All hematomas were without clinical consequences.

Topics: Abciximab; Adenosine; Aged; Antibodies, Monoclonal; Catheterization, Peripheral; Clopidogrel; Female; Hematoma; Hemorrhage; Hemostatic Techniques; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Punctures; Purinergic P2Y Receptor Antagonists; Radial Artery; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

Despite dual antiplatelet treatment, major ischemic events are common following ST elevation myocardial infarction (STEMI). We aimed to assess high platelet reactivity on aspirin (HPR-aspirin) and its association with P2Y12i (HPR-P2Y12i) during the acute phase of STEMI.. We included all consecutive patients admitted for STEMI treated by primary angioplasty in our center for 1year. All patients received a loading dose followed by a maintenance dose of aspirin (75mg/day) and prasugrel (ticagrelor or clopidogrel if contraindicated). Platelet reactivity was assessed 4±1days and 75±15days after admission using light transmission aggregometry with arachidonic acid (LTA-AA-HPR-aspirin) and VASP (HPR-P2Y12i) to define HPR as well as serum Thromboxane-B2 and LTA-ADP. Major cardiac and cerebrovascular events were recorded for 1year.. We included 106 patients - mean age was 61y.o., 76% were male and 20% had diabetes. STEMI was anterior in 52% and LV ejection fraction at discharge was 51±9%. 50% of patients were treated with prasugrel and 34% with ticagrelor. At day 4 after STEMI, HPR-aspirin was found in 26% patients and HPR-P2Y12i in 7%. HPR- both aspirin and P2Y12i was found in 4%. Diabetes and age were predictors of HPR-aspirin. HPR-aspirin was persistent 75days later in 36% patients. At 1year, 7.9% patients had experienced major adverse cardiovascular and cerebrovascular events (MACCE). HPR-aspirin and HPR on both aspirin and P2Y12i were significantly associated with MACCE.. HPR-aspirin is frequent just after STEMI and associated with MACCE especially when associated with HPR-P2Y12i.

Topics: Acute Disease; Adenosine; Aspirin; Blood Platelets; Brain Ischemia; Cardiovascular Diseases; Clopidogrel; Female; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Survival Analysis; Ticagrelor; Ticlopidine

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

Topics: Adenosine; Aged; Analgesics, Opioid; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morphine; Myocardial Reperfusion; Percutaneous Coronary Intervention; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Topics: Adenosine; Aged; Female; Humans; Magnetic Resonance Imaging; Male; Microvessels; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor

Pre-hospital ticagrelor, given less than 1h before coronary intervention (PCI), failed to improve coronary reperfusion in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary PCI. It is unknown whether a longer interval from ticagrelor administration to primary PCI might reveal any improvement of coronary reperfusion.. We retrospectively compared 143 patients, pre-treated in spoke centers or ambulance with ticagrelor at least 1.5h before PCI (Pre-treatment Group), with 143 propensity score-matched controls treated with ticagrelor in the hub before primary PCI (Control Group) extracted from RENOVAMI, a large observational Italian registry of more than 1400 STEMI patients enrolled from Jan. 2012 to Oct. 2015 (ClinicalTrials.gov id: NCT01347580). The median time from ticagrelor administration and PCI was 2.08h (95% CI 1.66-2.84) in the Pre-treatment Group and 0.56h (95% CI 0.33-0.76) in the Control Group. TIMI flow grade before primary PCI in the infarct related artery was the primary endpoint.. The primary endpoint, baseline TIMI flow grade, was significantly higher in Pre-treatment Group (0.88±1.14 vs 0.53±0.86, P=0.02). However in-hospital mortality, in-hospital stent thrombosis, bleeding rates and other clinical and angiographic outcomes were similar in the two groups.. In a real world STEMI network, pre-treatment with ticagrelor in spoke hospitals or in ambulance loading at least 1.5h before primary PCI is safe and might improve pre-PCI coronary reperfusion, in comparison with ticagrelor administration immediately before PCI.

Topics: Adenosine; Aged; Ambulances; Chi-Square Distribution; Coronary Angiography; Coronary Thrombosis; Electrocardiography; Emergency Medical Services; Female; Hemorrhage; Hospital Mortality; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Propensity Score; Proportional Hazards Models; Registries; Retrospective Studies; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Stents; Ticagrelor; Time Factors; Time-to-Treatment; Transportation of Patients; Treatment Outcome

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