Efficacy and safety of low-dose prasugrel as dual antiplatelet therapy in patients with ischemic heart disease: a systematic review and network meta-analysis of randomized controlled trials.

Abstract

Low-dose prasugrel could provide a better balance between adverse ischemic and bleeding events compared to other P2Y12 receptor inhibitors as part of dual antiplatelet therapy (DAPT) for patients with ischemic heart disease. This study evaluated these risks of adverse events associated with low-dose prasugrel and other P2Y12 receptor inhibitors. A network meta-analysis was conducted, searching for randomized controlled trials (RCTs) comparing clopidogrel (75 mg), low-dose (3.75 mg) and standard-dose (10 mg or 5 mg) prasugrel, or ticagrelor (180 mg). The primary endpoint was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, or stroke. The secondary endpoint was major bleeding, cardiovascular death, myocardial infarction, and stroke. Across 13 RCTs, neither low-dose prasugrel, standard-dose prasugrel, nor ticagrelor showed a statistically significant difference in MACE compared to clopidogrel [risk ratio (RR): 0.73, 95% confidence interval (CI) 0.49-1.09; RR: 0.86, 95% CI 0.68-1.09; RR: 1.02, 95% CI 0.62-1.67, respectively]. However, the standard dose of prasugrel was associated with a significantly higher risk of bleeding events compared to clopidogrel (RR, 0.72; 95% CI 0.35-1.49; RR, 1.26; 95% CI 1.01-1.58; RR, 1.26; 95% CI 0.82-1.96). The surface under the cumulative ranking curves was highest for low-dose prasugrel for both MACE and bleeding events (17.3 and 64.6 for clopidogrel, 84.5 and 84.9 for low-dose prasugrel, 62.0 and 11.8 for standard-dose prasugrel, and 36.2 and 38.7 for ticagrelor, respectively). Low-dose prasugrel may be a viable option in addition to standard P2Y12 receptor inhibitors.