Clopidogrel plus proton pump inhibitor linked with increased risk for rehospitalization

Patients assigned to clopidogrel and a proton pump inhibitor had increased risk for rehospitalization following an myocardial infarction or stent placement, results from a retrospective cohort analysis suggested.

Researchers from Irvine, Calif. and Seattle included patients enrolled in a multistate health insurance plan with Medicare and commercial clients. They evaluated adverse clinical outcomes in patients treated with clopidogrel (Plavix, Sanofi Aventis) plus a proton pump inhibitor (PPI) and compared them with patients assigned to clopidogrel alone. Cohorts were matched so that 1,033 patients were discharged from the hospital after experiencing MI or stent placement and were treated with clopidogrel plus a PPI, and 1,033 patients were discharged and treated with clopidogrel alone.

Patients assigned to clopidogrel plus a PPI had a 93% increase in risk for rehospitalization for MI (adjusted HR=1.93; 95% CI, 1.05-3.54) and also had a 64% increase in the risk for rehospitalization for MI or coronary stent placement (adjusted HR=1.64; 95% CI, 1.16-2.32) vs. patients assigned to clopidogrel alone. In a subgroup of patients assigned to clopidogrel and pantoprazole (Protonix, Pfizer; n=659), rehospitalization rates for MI or coronary stent placement were higher than in a matched group of patients assigned to clopidogrel alone (adjusted HR=1.91; 95% CI, 1.19-3.06).

“This study provides additional information supporting a potentially higher risk of adverse clinical outcomes in patients receiving clopidogrel with a PPI,” the researchers concluded. “These findings highlight the need for additional prospective randomized clinical studies to further evaluate clinical outcomes associated with a potential drug–drug interaction between clopidogrel and PPIs.”

Stockl KM. Arch Intern Med. 2010;170:704-710.