Efficacy and safety of P2Y12 inhibitors according to diabetes, age, gender, body mass index and body weight: systematic review and meta-analyses of randomized clinical trials

Abstract

Objective: The efficacy of antiplatelet drugs may differ in specific patient subgroups. We aimed to assess the efficacy and safety of the P2Y12 inhibitors clopidogrel, ticlopidine, prasugrel, ticagrelor, and cangrelor according to diabetes status, age, gender, body mass index, and body weight.

Methods: Randomized clinical trials (RCTs) of P2Y12 inhibitors reporting information on cardiovascular disease (defined as myocardial infarction, stroke, or cardiovascular death) and bleeding (defined as any bleeding) events among the subgroups diabetes and non-diabetes, age ≥65 and <65 year-old, men and women, body mass index ≥30 and <30 kg/m(2), and body weight ≥60 and <60 kg, were identified in Medline, Embase, Web of Science, and Cochrane Library on August 31st, 2014. For each inhibitor, random-effects meta-analyses were used to estimate the ratio of relative risks (rRR) for cardiovascular and bleeding events among patient subgroups.

Results: Twenty distinct RCTs (233 285 participants, 21 323 cardiovascular and 5183 bleeding events) were identified. Cardiovascular risk reduction with clopidogrel did not significantly differ according to diabetes (rRR: 1.04; 95% CI: 0.95 to 1.13; p = 0.395), age (0.98; 0.88 to 1.09; p = 0.347), gender (0.97; 0.90 to 1.04; p = 0.382), or body mass index (1.11, 0.95 to 1.31; p = 0.191). Results for other inhibitors were comparable, although available data were sparse. Limited data on bleeding events were available.

Conclusion: Data from RCTs did not show a different cardiovascular efficacy of clopidogrel in diabetes mellitus and other clinically relevant subgroups. Limited information was available on the efficacy and safety of other P2Y12 inhibitors in specific subgroups.

Keywords: Antiplatelet resistance; Clopidogrel; Diabetes; Meta-analysis; P2Y(12) inhibitors; Thienopyridines.