Prescribing proton pump inhibitor and clopidogrel together: current state of recommendations

Conflicting evidence has contributed to confusion regarding the safety of co-prescribing a proton pump inhibitor (PPI) and clopidogrel. This review will quantify the risk of gastrointestinal bleeding associated with common cardioprophylactic regimens, review the evidence regarding a PPI-clopidogrel interaction and assess its clinical relevance, and reinforce best-practice recommendations for gastrointestinal bleeding prevention among patients prescribed clopidogrel.

The COGENT trial confirmed a substantial reduction in gastrointestinal bleeding risk without apparent increase in cardiovascular events when clopidogrel was co-prescribed with omeprazole. These data are consistent with secondary data analyses of large cardiovascular trials and well adjusted observational studies that also failed to confirm a consistent, clinically relevant increase in cardiovascular endpoints or mortality. Individual genetic variations in drug metabolism may contribute to increased cardiac event rates observed in small subsets of the population when PPI is co-prescribed. In the future, pharmacogenomics and point-of-care testing will likely play an emerging role in individualizing prescription strategy.

A pragmatic approach dictates an explicit risk-benefit assessment prior to co-prescription to maximize cardiac benefit and minimize the risk of gastrointestinal bleeding.