Comparative Efficacy and Safety of Oral P2Y ₁₂ Inhibitors in Acute Coronary Syndrome

Abstract

Background: New randomized, controlled trials have become available on oral P2Y 12 inhibitors in acute coronary syndrome. We aimed to evaluate current evidence comparing the efficacy and safety profile of prasugrel, ticagrelor, and clopidogrel in acute coronary syndrome by a meta-analysis of randomized controlled trials. Methods: We performed a network meta-analysis and direct pairwise comparison analysis of efficacy and safety outcomes from 12 randomized controlled trials including a total of 52 816 patients with acute coronary syndrome. Results: In comparison with clopidogrel, ticagrelor significantly reduced cardiovascular mortality (hazard ratio [HR], 0.82 [95% CI, 0.72–0.92]) and all-cause mortality (HR, 0.83 [95% CI, 0.75–0.92]), whereas there was no statistically significant mortality reduction with prasugrel (HR, 0.90 [95% CI, 0.80–1.01] and HR, 0.92 [95% CI, 0.84–1.02], respectively). In comparison with each other, there were no significant differences in mortality (HR prasugrel versus ticagrelor, 1.10 [95% CI, 0.94–1.29] and 1.12 [95% CI, 0.98–1.28]). In comparison with clopidogrel, prasugrel reduced myocardial infarction (HR, 0.81 [95% CI, 0.67–0.98]), whereas ticagrelor showed no risk reduction (HR, 0.97 [95% CI, 0.78–1.22]). Differences between prasugrel and ticagrelor were not statistically significant. Stent thrombosis risk was significantly reduced by both ticagrelor and prasugrel versus clopidogrel (28%–50% range of reduction). In comparison with clopidogrel, both prasugrel (HR, 1.26 [95% CI, 1.01–1.56]) and ticagrelor (HR, 1.27 [95% CI, 1.04–1.55]) significantly increased major bleeding. There were no significant differences between prasugrel and ticagrelor for all outcomes explored. Conclusions: Prasugrel and ticagrelor reduced ischemic events and increased bleeding in comparison with clopidogrel. A significant mortality reduction was observed with ticagrelor only. There was no efficacy and safety difference between prasugrel and ticagrelor. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/ ; Unique identifier: CRD42019155648.

Five-Year Comparative Efficacy of Everolimus-Eluting vs. Resolute Zotarolimus-Eluting Stents in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

“…ACS is associated with higher risk of adverse outcomes owing to the proinflammatory state and higher atherosclerotic burden [ 16 ]. Besides pharmacological and technology advancement, a persistent risk of adverse events remains over the 1 year period after an ACS event [ 15 , 28 , 29 ]. Thus, a DES design aimed to provide a more biocompatible polymer and a better polymer/drug elution balance remains a pivotal goal in ACS [ 21 , 30 ].…”

The year in cardiovascular medicine 2020: interventional cardiology

“…There was no efficacy or safety difference between prasugrel and ticagrelor. 99 A Korean randomized trial in ACS patients undergoing PCI showed that a prasugrel-based dose de-escalation strategy, starting 1 month after PCI, reduced the risk of net clinical outcomes up to 1 year, mainly driven by a reduction in bleeding without an increase in ischaemic events. 100 Regarding the optimal timing of P2Y12 inhibitors administration, an RCT including 1449 ACS patients found no differences in clinical outcomes between a downstream and an upstream antiplatelet treatment strategy.…”

De-escalation of antiplatelet therapy — an approach to improve safety and efficacy of treatment in patients after acute coronary syndrome

“…1 The GREAT Network Italy 1. w.kochman@icloud.com 2. salvatore.disomma@uniroma1.it Dual antiplatelet treatment (DAPT) with aspirin and P2Y12 inhibitor -clopidogrel has been shown to reduce risk of ischemic events in patients after acute coronary syndrome (ACS) [1][2][3]. Further studies proved superiority of ticagrelor and prasugrel over clopidogrel in this clinical setting [4][5][6]. It has been also demonstrated that prolongation of DAPT over one year with lower doses of P2Y12 inhibitor may further improve clinical outcome in patients with previous ACS [7].…”

“…The study was designed to evaluate safety and efficacy of ticagrelor dose reduction with or without continuation of aspirin versus DAPT with standard dose ticagrelor in ACS patients. The strategy proposed in the ELECTRA-SIRIO 2 study does not require a platelet reactivity testing, making de-escalation more feasible for a wide clinical application [24][25][26][27][28]. The study population will comprise of 4,500 patients consecutively admitted to the study centres due to ACS, including patients with ST-elevation myocardial infarction, non-ST-elevation myocardial infarction and unstable angina [24].…”