Efficacy and safety of newer P2Y12 inhibitors for acute coronary syndrome: a network meta-analysis

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.

Figure 1

Network profile for the studies comparing different P2Y₁₂ inhibitors involved in DAPT. Each line represents a pair of direct comparison between different P2Y₁₂ inhibitors. The width of the lines is proportional to the number of trials comparing every pair of treatments, and the size of every circle is proportional to the number of randomly assigned participants (sample size).

Figure 2

Forest plots assessing the effects of different P2Y₁₂ inhibitors relative to clopidogrel. (A) Cardiovascular mortality. (B) Myocardial infarction. (C) Stroke. (D) MACE. (E) Definite or probable stent thrombosis. (F) All-cause mortality. MACE = major adverse cardiovascular events. Square markers indicate odds ratios for cardiovascular outcomes comparing different P2Y₁₂ inhibitors to clopidogrel. The horizontal lines indicate 95% confidence intervals.