Concomitant Proton-Pump Inhibitors With Antiplatelet Drugs Requires Caution Interview with:
José C. Nicolau, MD, PhD, FACC
Professor -University of São Paulo Medical School
Director – Acute Coronary Disease Unit, Heart Institute

MedicalResearch: What is the background for this study?

Dr. Nicolau: Previous studies, mainly performed in patients undergoing percutaneous coronary intervention (PCI), have shown that concomitant use of proton-pump inhibitors (PPIs) diminishes the antiplatelet effect of the drug clopidogrel. This diminished response to clopidogrel has in turn been associated with an increased risk of stent thrombosis and ischemic events. Our paper presented results from a secondary analysis performed in patients enrolled in the TRILOGY ACS randomized clinical trial. Our study is the first to examine the influence of interactions between PPIs and clopidogrel or the newer, more potent antiplatelet drug prasugrel, as well as correlations with platelet reactivity and clinical outcomes in high-risk patients who were receiving medical management without revascularization following acute coronary syndrome (ACS).

MedicalResearch: What are the main findings?

Dr. Nicolau: Among patients who were receiving proton-pump inhibitors at baseline (23% of total), the adjusted hazard ratio (HR) for the composite outcome of cardiovascular death/myocardial infarction/stroke was 0.73 (95% CI, 0.54-0.98) when comparing prasugrel with clopidogrel. Among patients who were not taking PPIs, the HR was 1.01(95% CI, 0.85-1.19). The main factor driving these results was myocardial infarction (HR=0.61 [95% CI, 0.42-0.88]; P for interaction=0.012). These findings could not be explained by the results obtained in a subgroup of patients who participated in platelet reactivity testing.

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Nicolau: We need to be careful with the concomitant utilization of clopidogrel and proton-pump inhibitors.

MedicalResearch: What recommendations do you have for future research as a result of this study?

Dr. Nicolau: Additional studies are needed to delineate optimal antiplatelet strategies in high-risk Acute Coronary Syndrome patients who are managed medically without revascularization and who also require long-term proton-pump inhibitors therapy.


Concomitant proton-pump inhibitor use, platelet activity, and clinical outcomes in patients with acute coronary syndromes treated with prasugrel vs. clopidogrel and managed without revascularization: Insights from the TRILOGY ACS Trial

Nicolau, Jose Carlos et al.

American Heart Journal

Received: December 22, 2014; Accepted: May 31, 2015; Published Online: June 10, 2015 Publication stage: In Press Accepted Manuscript