Systematic review with meta-analysis: the risk of gastrointestinal bleeding in patients taking third-generation P2Y12 inhibitors compared with clopidogrel

Abstract

© 2018 John Wiley & Sons Ltd Background: Ticagrelor and prasugrel are third-generation oral P2Y 12 receptor antagonists with rapid onset and pronounced platelet inhibition. However, higher overall bleeding rates have been reported for these agents when compared with clopidogrel. Aim: To compare the risk of gastrointestinal bleeding (GIB) among users of third-generation P2Y 12 inhibitors with clopidogrel. Methods: We systematically searched for published randomised controlled trials of ticagrelor or prasugrel versus clopidogrel until September 2018. The primary outcome was the risk of GIB among users of third-generation P2Y 12 inhibitors when compared to clopidogrel, expressed as risk ratio (RR) and 95% confidence interval (CI). The rates of non-coronary artery bypass graft (CABG) major bleeding, life-threatening bleeding, fatal bleeding, and intracranial bleeding were analysed as secondary outcomes. Results: Forty-one studies were included in the analysis of non-CABG major bleeding, of which 12 were included in the analysis of GIB including 58 678 patients. Third-generation P2Y 12 inhibitors were associated with higher risk of GIB as compared with clopidogrel (RR 1.28, 95% CI 1.13-1.46). The findings were consistent for upper (RR 1.32, 95% CI 1.05-1.67) and unspecified GIB (RR 1.25, 95% CI 1.01-1.53), but not lower GIB (RR 1.25, 95% CI 0.95-1.65). Subgroup analysis showed higher GIB risk in prasugrel studies (RR 1.40, 95% CI 1.10-1.77) than in ticagrelor studies (RR 1.15, 95% CI 0.94-1.39). Third-generation P2Y 12 inhibitors also increased the risk of non-CABG major bleeding (RR 1.18, 95% CI 1.08-1.28). Conclusion: Third-generation P2Y 12 inhibitors were associated with increased risk of GIB and non-CABG major bleeding when compared with clopidogrel.