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

• Published in: Journal of internal medicine Vol. 271; no. 3; pp. 257 - 263
• Main Authors: Burkard, T., Kaiser, C. A., Brunner-La Rocca, H., Osswald, S., Pfisterer, M. E., Jeger, R. V.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-03-2012; Blackwell
• Subjects: Aged; Angioplasty, Balloon, Coronary - methods; antiplatelet therapy; Aspirin - adverse effects; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular Diseases - therapy; coronary artery disease; Coronary heart disease; Diseases of the cardiovascular system; Drug Interactions; Drug Therapy, Combination; Drug-Eluting Stents; Female; General aspects; Heart; Humans; Kaplan-Meier Estimate; Male; Medical sciences; Middle Aged; myocardial infarction; Myocardial Infarction - chemically induced; percutaneous coronary intervention; Platelet Aggregation Inhibitors - adverse effects; Proton Pump Inhibitors - adverse effects; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Retrospective Studies; Risk Factors; Ticlopidine - adverse effects; Ticlopidine - analogs & derivatives; Myocardial infarction; coronary artery disease; Trial; Angioplasty; Report; Rate; Coronary artery; Instrumentation therapy; Cardiovascular disease; antiplatelet therapy; Myocardial disease; Coronary heart disease; Stent; Antiplatelet agent; Proton pump inhibitor; Medicine; Chemotherapy; percutaneous coronary intervention; Treatment; Association; Antithrombotic agent; Clopidogrel; Clinical trial; Thienopyridine derivative
• ISSN: 0954-6820; 1365-2796
• DOI: 10.1111/j.1365-2796.2011.02423.x

.  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: 257–263.
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 Effektivitäts 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 patients with available discharge medication 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 be woman (80% vs. 69%, P = 0.009) and have a history of diabetes (29.6% vs. 17.3%, P = 0.002) or gastrointestinal ulcer 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 the only independent risk factors for MI.
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 an independent predictor of outcome emphasizing the clinical importance of this drug–drug interaction.