Publications of the Week, August 10

Comparison of different types of P2Y₁₂ inhibitors in acute coronary syndrome

In patients with an acute coronary syndrome who are receiving acetylsalicylic acid (ASA), there are 3 oral P2Y₁₂ inhibitors that have been studied as a complementary antiplatelet therapy: clopidogrel, prasugrel, and ticagrelor. Although clopidogrel is widely used, the newer P2Y₁₂ inhibitors (prasugrel and ticagrelor) are more potent antiplatelet agents, have a faster onset of action, and carry a lesser potential for interindividual variability in terms of therapeutic effect. This meta-analysis compared the efficacy and safety profile of clopidogrel, prasugrel, and ticagrelor in patients with an acute coronary syndrome when added to ASA therapy.

A network meta-analysis and direct pairwise comparison analysis were done to assess the efficacy and safety outcomes from 12 randomized controlled trials that involved 52,816 patients with an acute coronary syndrome.

1. Mortality: As compared with clopidogrel, ticagrelor was associated with a significant reduction in 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 prasugrel did not confer a reduction in cardiovascular mortality (HR, 0.90; 95% CI, 0.80-1.01) or all-cause mortality (HR, 0.92; 95% CI, 0.84-1.02).
2. Ischemic outcomes: When compared with clopidogrel, prasugrel was associated with a significant reduction in myocardial infarction (HR, 0.81; 95% CI, 0.67-0.98), whereas ticagrelor was not associated with a reduced risk for myocardial infarction (HR, 0.97; 95% CI, 0.78-1.22). The risk for definite or probable stent thrombosis was significantly reduced by both prasugrel (HR, 0.50; 95% CI, 0.38-0.64) and ticagrelor (HR, 0.72; 95% CI, 0.58-0.90).
3. Bleeding: Both prasugrel (HR, 1.26; 95% CI, 1.01-1.56) and ticagrelor (HR, 1.27; 95% CI, 1.04-1.55) were associated with a significantly higher risk for major bleeding than clopidogrel.

When prasugrel was compared with ticagrelor, there were no differences in efficacy and safety but prasugrel was associated with a nonsignificant higher rate of cardiovascular mortality (HR, 1.10; 95% CI, 0.94-1.29) and all-cause mortality (HR, 1.12; 95% CI, 0.98-1.28).

The authors concluded that prasugrel and ticagrelor are more effective than clopidogrel in reducing the risk for ischemic outcomes but both agents confer a higher bleeding risk than clopidogrel; as compared with clopidogrel, a greater mortality reduction was observed with ticagrelor than with prasugrel; and no significant differences were apparent between prasugrel and ticagrelor in the explored outcomes.