Objectives To perform a meta-analysis in order to determine safety of concomitant use of clopidogrel and proton pump inhibitors (PPIs) in patients undergoing percutaneous coronary intervention (PCI).
Methods References (including original papers, conference abstracts and unpublished studies) for randomized or observational studies reporting the risk of cardiovascular events and mortality with and without PPIs exposure in patients taking clopidogrel after PCI were searched in MEDLINE, SCIE, OVID, EMBASE, Cochrane Controlled Trials Register, CBM, and CNKI. Fixed-effects model or random-effects model was used according to heterogeneity of studies, and subgroup analysis was performed by stratifying the available data using patient number, length of follow-up and race-assessed.
Results Fourteen cohort studies covering 34,967 patients met the selection criteria. There was substantial heterogeneity in revascularization, recurrence of acute coronary syndrome (ACS) and all-cause mortality. Concomitant use of clopidogrel and PPIs corresponded to an 113% increase in risk of in-stent restenosis [risk ratio (RR) = 2.13, 95% confidence intervals (CI) = 1.44-3.16], a 42% increase in the risk of recurrent ACS (RR = 1.42, 95% CI = 1.15-1.77) and a 64% increase in the risk of all-cause mortality (RR = 1.64, 95% CI = 1.09-2.46). In contrast, no significant association between PPIs use and revascularisation (RR = 1.14, 95% CI = 0.99-1.31), cardiovascular death (RR = 1.06, 95% CI = 0.75-1.50) and stent thrombosis (RR = 1.25, 95%CI = 0.92-1.72) has been found.
Conclusions Concomitant use of clopidogrel and PPIs after PCI may be associated with increased risks of in-stent restenosis, recurrent ACS, and all-cause mortality, but does not influence the risk of revascularisation, cardiovascular death and stent thrombosis. Randomized trials are required to confirm the above findings.