Clopidogrel, Proton-Pump Inhibitors, and Cardiovascular Events

A careful analysis of drug exposure after coronary stent implantation found no significant association between major cardiovascular events and concomitant use of clopidogrel and PPIs.

Concerns about the combined use of clopidogrel and proton-pump inhibitors (PPIs) began when studies suggested that PPIs impaired the intended antiplatelet activity of clopidogrel. This effect was attributed to a competitive interaction at the cytochrome P450 pathway, which is required for the biotransformation of the prodrug clopidogrel to its active metabolite. These studies led to a rapid onslaught of retrospective observational database analyses that reported an increased likelihood of clinical adverse cardiovascular events in patients taking this drug combination. However, a fundamental problem with these retrospective analyses has been their reliance on discharge prescription data, without accounting for varying medication exposures after discharge.


Now, investigators analyzed outcomes of 23,200 patients who underwent uncomplicated cardiac stent placement according to their postdischarge drug exposures. Using data from the Veterans Affairs Pharmacy Benefits Management database, the researchers noted gaps in clopidogrel and PPI use and performed a daily reconciliation of medication exposures for each patient. Omeprazole was the most commonly prescribed PPI (88%); esomeprazole, lansoprazole, rabeprazole, and pantoprazole accounted for the remainder of PPI prescriptions.

Continuous exposure to clopidogrel with concomitant use of PPIs in patients after percutaneous coronary intervention was not associated with increased risk for major adverse cardiovascular events, the primary endpoint of the study. The hazard ratios of adverse cardiovascular outcomes overall replicated the concerns of increased risks associated with concomitant use of clopidogrel and a PPI. However, after the authors used propensity-matched evaluations to correct for covariate cardiovascular risks, they found no significant association between major cardiovascular events and use of clopidogrel with continuous, switched, or discontinued PPIs.


Citation(s):

Banerjee S et al. Effect of concomitant use of clopidogrel and proton pump inhibitors after percutaneous coronary intervention. Am J Cardiol 2011 Jan 20; [e-pub ahead of print].