Combined clopidogrel and proton pump inhibitor therapy is associated with higher cardiovascular event rates after percutaneous coronary intervention: a report from the BASKET trial

Burkard T, Kaiser CA, Brunner-La Rocca H, Osswald S, Pfisterer ME, Jeger RV for the BASKET Investigators (Cardiology, University Hospital; and Cardiology, Maastricht University Hospital Center, Maastricht, the Netherlands). Combined clopidogrel and proton pump inhibitor therapy is associated with higher cardiovascular event rates after percutaneous coronary intervention: a report from the BASKET trial. J Intern Med 2012; 271: 257263. Objective. To investigate whether there is an increased risk of cardiac events with a combined therapy of clopidogrel and proton pump inhibitors (PPIs) after percutaneous coronary intervention(PCI). Design. In the BAsel Stent Kosten Effektivitats Trial (BASKET), all patients undergoing PCI received 6 months of clopidogrel and were analysed for the use of PPI therapy. Endpoints were major adverse cardiac events (MACE), myocardial infarction (MI), death and target vessel revascularization (TVR) after 36 months. Results. Of 801 patientswith available dischargemedication data, 109 (14%) received PPIs. Patients who received PPIs were older (66.5 +/- 10.5 vs. 63.3 +/- 11.3 years, P = 0.006), more likely to bewoman (80% vs. 69%, P = 0.009) and have a history of diabetes (29.6% vs. 17.3%, P = 0.002) orgastrointestinalulcer disease (8.3% vs. 3.3%, P = 0.015) and more often received nonsteroidal anti-inflammatory drugs (7.3% vs. 2.2%, P = 0.003) and corticosteroids (11% vs. 3.6%, P = 0.001) but not aspirin (91.7% vs. 97%, P = 0.008) compared with those who did not receive PPIs. Patients who received PPI therapy had higher rates of MACE (30.3% vs. 20.8%, P = 0.027) and MI (14.7% vs. 7.4%, P = 0.01) but similar rates of death (9.2% vs. 7.4%, P = 0.51) and TVR (20.2% vs. 15.3%, P = 0.2) compared with those who did not. By multivariate analysis, diabetes (hazard ratio 1.83, 95% confidence interval 1.07-3.15) and PPI use (hazard ratio 1.88, 95% confidence interval 1.05-3.37) were theonly independent riskfactors forMI. Conclusion. In a real-world PCI population, the combination of PPIs and clopidogrel was associated with a doubling of MI rates after 3 years. Even after correction for confounding factors, concomitant PPI use remained anindependent predictor ofoutcome emphasizing the clinical importance of this drug-drug interaction.