Abstract 11290: Risk of Adverse Cardiovascular Events with Concomitant Use of Proton Pump Inhibitors and Clopidogrel: A Meta-Analysis
Background: Recent pharmacodynamic data has suggested significant interactions between clopidogrel (C) and proton pump inhibitors (PPI), leading to possible reduced antiplatelet efficacy of clopidogrel. Whether this interaction translates into any significant clinical effect remains controversial since studies have shown conflicting results. We conducted a meta-analysis of available data to assess the clinical outcome associated with the combined use of C + PPI.
Methods: Two independent reviewers searched MEDLINE, EMBASE, Cochrane central register and abstracts of pertinent scientific meetings (ACC, AHA, DDW and ACG; 2006–2010). Studies were included if it evaluated clinical outcomes in patients who received C+PPI in comparison to C alone. The results of these studies were combined and a pooled relative risk ratio (RR) and 95% confidence interval (95% CI) and hetergeneity were derived using random effects estimate.
Results: 11 observational studies (OS) with 74,534 patients and 3 randomized controlled trials (RCTs) with 11,475 patients met our inclusion criteria. In comparison to C+PPI, use of C alone in OS was associated with following: reduced risk of MI, RR 0.64 (95% CI, 0.51–0.79; Chi2= 43.50, p< 0.0001, I2= 82%); MACE, RR 0.73 (95% CI, 0.67–0.80; Chi2= 39.20, p< 0.0001, I2= 74%). In RCT's, use of C alone in comparison to C+PPI was associated with: no difference in risk of MI, RR 1.01 (95% CI, 0.87–1.17; Chi2= 0, p=0.97, I2= 0; no difference in MACE, RR of 0.89 (95% CI 0.62–1.27; Chi2= 8.02, p< 0.02, I2= 75%)
Conclusions: The results derived from RCTs differ from those of OS. While OS are limited by lack of control for confounding factors and heterogeneity, RCTs (although few in number and underpowered) show no statistically significant treatment interaction for clinical events. Because of these outcome differences, more well-powered, prospective RCTs are needed to better clarify the effect of potential interaction of combined C + PPI use on clinical events.
- © 2010 by American Heart Association, Inc.