Oral P2Y12 Inhibitors Prasugrel Research Articles

Meta-Analysis Comparing Potent Oral P2Y12 Inhibitors versus Clopidogrel in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

BackgroundIn patients with atrial fibrillation (AF) receiving percutaneous coronary intervention (PCI), current guidelines recommend against combining potent oral P2Y12 inhibitors (i.e. ticagrelor or prasugrel) with oral anticoagulant (OAC) therapy, but the evidence is limited.ObjectiveThe aim of this meta-analysis was to compare the efficacy and safety of potent oral P2Y12 inhibitors with clopidogrel in patients receiving OAC therapy for AF after a recent PCI.MethodsElectronic databases were searched for randomized controlled trials (RCT) reporting outcomes according to the P2Y12 inhibitor used. Major or clinically relevant non-major bleeding were the safety endpoints, while the efficacy outcomes were major adverse cardiovascular events (MACE). The potent oral P2Y12 inhibitors prasugrel and ticagrelor were compared with clopidogrel. A subgroup analysis was conducted to evaluate the differences between patients treated with dual antithrombotic therapy (DAT) versus triple antithrombotic therapy (TAT).ResultsFour RCTs that included 10,057 patients were included in this analysis. Potent oral P2Y12 inhibitors were associated with a significant increase in major or clinically relevant non-major bleeding compared with clopidogrel (risk ratio [RR] 1.30, 95% confidence interval [CI] 1.06–1.59, p = 0.01; number needed to harm 18, 95% CI 12–36). This finding was consistent regardless of the concomitant antithrombotic therapy (DAT vs. TAT; p = 0.69). The risk of MACE did not differ between potent oral P2Y12 inhibitors and clopidogrel (RR 1.02, 95% CI 0.57–1.82).ConclusionsIn patients receiving OAC therapy for AF after a recent PCI, potent oral P2Y12 inhibitors increase the risk of clinically relevant bleeding compared with clopidogrel, with no evident benefit in terms of MACE reduction.Electronic supplementary materialThe online version of this article (10.1007/s40256-020-00436-8) contains supplementary material, which is available to authorized users.

Efficacy and safety of potent platelet P2Y12 receptor inhibitors in elderly versus nonelderly patients with acute coronary syndrome: A systematic review and meta-analysis

The use of the potent oral P2Y12 inhibitors prasugrel and ticagrelor in patients with acute coronary syndromes (ACS) has a favorable net clinical effect compared with clopidogrel and is recommended as first-line therapy. However, the impact of these agents on ischemic and bleeding events in elderly ACS patients is not well defined. We performed a systematic review of articles comparing potent P2Y12 inhibitors to clopidogrel in elderly and nonelderly patients (defined according to each study) with ACS in terms of efficacy (composite of cardiovascular death, myocardial infarction, or stroke) and safety (major bleeding) end points. A total of 7,860 elderly and 37,857 nonelderly patients from 7 studies (5 randomized control trials and 2 observational studies) were included. Potent P2Y12 inhibitors significantly reduced efficacy end point in nonelderly patients (relative risk [RR] 0.85, 95% CI 0.79-0.93) and less so in elderly patients (RR 0.95, 95% CI 0.86-1.05). No significant differences were found between potent P2Y12 inhibitors and clopidogrel in terms of safety end point in both elderly (RR 1.19, 95% CI 0.95-1.49) and nonelderly patients (RR 1.16, 95% CI 0.95-1.41). There were no significant interactions between age and treatment effect in both analyses (efficacy Pint=.16; safety Pint=.83). The effect of more potent P2Y12 inhibitors compared with clopidogrel on efficacy and safety end points is consistent in elderly and younger patients. These data imply that potent P2Y12 inhibitors should not be withheld from eligible patients solely because of advanced age.

The mortality benefit seen with the newer more potent oral P2Y12 inhibitors prasugrel and ticagrelor over clopidogrel is dependent on the underlying risk: A class effect as suggested by a meta-regression analysis

BackgroundThe two newer oral P2Y12 inhibitors prasugrel and ticagrelor have proven superior to clopidogrel in the treatment of acute coronary syndrome (ACS). The extent to which the reduction in mortality seen with ticagrelor is confined to this particular agent is hard to judge by simply looking at the overall study results as the study populations were composed of different cohorts at substantially different risk of death. MethodsA meta-regression technique was applied to 12 distinctive patient cohorts, six for each of prasugrel and ticagrelor, to investigate differential effects on mortality of P2Y12 inhibitors. ResultsData for the analysis cohorts, totalling 37,372 patients, were extracted from publications and cover a widely comparable spectrum of patient types, defined by the type of ACS and treatment strategy. The meta-regression lines for cardiovascular mortality with prasugrel or ticagrelor (each versus clopidogrel), as well as for both agents pooled, indicate a linear relationship with increasing benefit seen with higher underlying risk (p=0.007, 0.021 and 0.003, and R2=0.87, 0.77 and 0.62, respectively). ConclusionsIn the ACS patients studied, we found a mortality benefit with the two newer oral P2Y12 inhibitors prasugrel and ticagrelor when compared with clopidogrel, which increases progressively as the underlying risk of death increases. This appears to be a class effect for these two newer agents.

Rapid P2Y 12 Inhibition

Acute coronary syndrome (ACS) is still a serious condition associated with decreased quality of life, increased healthcare expenditures, and premature death. The prevalence of ACS is expected to increase with aging of the population and with the epidemics of obesity and diabetes. The short- and long-term mortality after an ACS has been dramatically reduced by the development of revascularization techniques and new antithrombotic agents. The past decade has seen many trials evaluating new oral and parenteral antiplatelet agents with greater potency than aspirin and clopidogrel. Several antiplatelet agents have been developed, with the ultimate goal to obtain optimal antiplatelet therapy for both the acute and the chronic phases of disease. Articles see p 336, 347 Ideally, efficiency requires several pharmacodynamic proprieties, such as a fast onset of action (immediate onset for emergency situations), a strong degree of platelet inhibition (at least stronger than the standard of care [aspirin and clopidogrel]), a narrow interindividual variability with no impact of genetic variants and no drug-to-drug interaction, and an easy administration (an oral drug for maintenance therapy and an intravenous formulation for rapid loading). Of course, this drug should also lead to a convincing reduction of recurrent ischemic events in an adequately powered phase 3 trial. With regard to safety, the illusion of having the same dose of a single antiplatelet drug to treat all clinical situations has passed. The degree of platelet activation and aggregation is different across clinical situations (eg, acute ST-segment–elevation myocardial infarction [STEMI] versus secondary prevention) and varies over time in the same patient. Recent large phase 3 trials have confirmed the importance of dosing and the target population treated with the new agents.1–4 From a safety standpoint, an ideal antiplatelet agent would also have an intravenous and oral formulation, with different doses tested in …