Thirteen studies were included in the review. Nine studies (88,643 participants, range 1,053 to 24,702) assessed effects on clinical endpoints and four studies (1,718 participants, range 140 to 1,000) assessed effects on platelet function. Study designs included randomised controlled trials (five studies), retrospective cohorts (five studies), nested case control (one study) and cross sectional (two studies). Reported follow-up times ranged from 106 days to 521 days for assessment of clinical endpoints and seven to 15 days for assessment of platelet function.
In observational studies, there was a significant increase in risk of cardiovascular death, readmission for myocardial infarction, acute coronary syndrome and non-fatal stroke with clopidogrel and proton pump inhibitors when compared with clopidogrel alone with fixed-effect (RR 1.40, 95% CI 1.15 to 1.70; Ι²=96%; four studies) and random-effects (RR 1.49, 95% CI 1.43 to 1.55; Ι²=96%; four studies) analyses. Randomised controlled studies showed no evidence of significant differences in clinical endpoints between the two treatment groups in fixed-effect (RR 1.20, 95% CI 0.82 to 1.76; Ι²=67%; three studies) and random-effects (RR 1.03, 95% CI 0.91 to 1.18; Ι²=67%; three studies) analyses. One nested case control study reported that use of proton pump inhibitors in patients prescribed with clopidogrel increased the risk of reinfarction compared to clopidogrel alone (RR 1.27, 95% CI 1.03 to 1.57).
Using various methods, co-administration of clopidogrel with proton pump inhibitors was associated with attenuation of the antiplatelet effect of clopidogrel alone (four studies); figures for each study were provided in the paper.