One abstract of an RCT (n=3,627 patients) and nine retrospective studies (n=67,650 patients) were included in the review. The RCT was double-blind and placebo-controlled. Given their retrospective design, most of the included studies were considered to be at risk of bias.
Dual antiplatelet therapy (clopidogrel and aspirin) with proton-pump inhibitors exposure resulted in a statistically significant reduction in adverse gastrointestinal events (OR 0.38, 95% CI 0.21 to 0.68; seven studies; I2=17%). With uncertain aspirin exposure in two studies, the direction of effect was similar (OR 0.34, 95% CI 0.14 to 0.87) but with substantial heterogeneity (I2=73%). Pooled results for the nine studies remained statistically significant (OR 0.40, 95% CI 0.28 to 0.58; I2=27%). The number of patients needed to treat per year to prevent one additional hospitalisation for gastrointestinal bleed was 239 (95% CI 199 to 342) for low gastrointestinal risk category patients, and 37 (95% CI 30 to 53) for high gastrointestinal risk category patients.
The pooled result for studies reporting upper gastrointestinal bleeds with any exposure to clopidogrel plus proton-pump inhibitors was statistically significant (OR 0.31, 95% CI 0.19 to 0.51; nine studies; I2=27%). The result for clopidogrel monotherapy (two studies) was not statistically significant.