Abstract
Whether newer P2Y12 inhibitors are more efficacious and safer than clopidogrel and whether there is a superior one remain uncertain. We compared the effect of P2Y12 inhibitors on clinical outcomes in patients with acute coronary syndrome (ACS). Randomized controlled trials comparing clopidogrel, prasugrel, ticagrelor, or cangrelor, in combination with aspirin were searched. Sixteen trials with altogether 77,896 patients were included. Compared to clopidogrel, cardiovascular mortality was reduced with prasugrel (OR 0.85, 95% CI 0.75–0.97) and ticagrelor (0.82, 0.73–0.93). Myocardial infarction (0.75, 0.63–0.89) and major adverse cardiovascular events (0.80, 0.69–0.94) were reduced by prasugrel. Stent thrombosis was reduced by prasugrel (0.49, 0.38–0.63), ticagrelor (0.72, 0.57–0.90), and cangrelor (0.59, 0.43–0.81). It was reduced more by prasugrel than ticagrelor (0.69, 0.51–0.93). There were more major bleeds with prasugrel (1.24, 1.05–1.48). Thrombolysis in Myocardial Infarction (TIMI) major bleeding was increased with prasugrel compared to clopidogrel (1.36, 1.11–1.66) and ticagrelor (1.33, 1.06–1.67). TIMI minor bleeding was increased with prasugrel (1.44, 1.16–1.77) and cangrelor (1.47, 1.01–2.16) compared to clopidogrel while it was increased with prasugrel compared to ticagrelor (1.32, 1.01–1.72). Prasugrel is preferable to those ACS patients at low bleeding risk to reduce cardiovascular events whereas ticagrelor is a relatively safe antiplatelet drug of choice for most patients.
Highlights
The efficacy and safety of newer P 2Y12 inhibitors in acute coronary syndrome (ACS) influenced the recommendations in the clinical guidelines
In the 2016 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on dual antiplatelet therapy (DAPT), ticagrelor was recommended over clopidogrel as a maintenance therapy in patients with non-ST-segment elevation (NSTE)-ACS or ST-segment elevation myocardial infarction (STEMI) receiving DAPT after percutaneous coronary intervention (PCI), while prasugrel was recommended for those patients at low bleeding risk and without prior stroke or
Doubling loading or maintenance dose of clopidogrel was used in the Thrombocytes And IndividuaLization of ORal antiplatelet therapy in percutaneous coronary intervention (TAILOR)[32] and Xiong et al.[33] trials; two doses of ticagrelor therapy rather than different P2Y12 inhibitors were compared in the Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction 54 (PEGASUS-TIMI 54) t rial[15]; ticagrelor was compared with placebo rather than the other P 2Y12 inhibitors in the Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study (THEMIS) trial[34], so these trials were excluded
Summary
The efficacy and safety of newer P 2Y12 inhibitors in ACS influenced the recommendations in the clinical guidelines. The 2017 European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) guideline recommended ticagrelor for ACS patients at moderate to high ischemic risk regardless of the initial treatment, but prasugrel for ACS patients undergoing PCI if there is no excess fatal bleeding or other contraindications (Class I)[17]. There have been several randomized controlled trials (RCTs) comparing the efficacy and safety of newer P2Y12 inhibitors with that of clopidogrel in patients with ACS, there were no head-to-head trials between newer P2Y12 inhibitors until the report of the two recent trials directly comparing prasugrel with ticagrelor[18,19]. It is necessary to update the efficacy and safety profiles of P 2Y12 inhibitors in ACS patients, to assess the comparative effectiveness among newer P2Y12 inhibitors. We performed a network meta-analysis to compare the effect of P 2Y12 inhibitors on cardiovascular and bleeding events in patients with ACS in order to optimize therapy in clinical practice
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