ProtonPump Inhibitor Prevacid Did Not Affect Antiplatelet Therapy in PRODIGY Trial Interview with:
Giuseppe Gargiulo MD

Research fellow in Cardiology
Inselspital, University of Bern,
Bern, Switzerland What is the background for this study? What are the main findings?

Dr. Gargiulo: Every year millions of people with coronary artery disease are treated worldwide with percutaneous coronary intervention (PCI). Consequently, they receive a dual  (DAPT) in order to prevent thrombotic life-threatening complications, such as stent thrombosis. DAPT often consists of aspirin and clopidogrel, but some studies have questioned the efficacy of clopidogrel in case of concomitant therapy with proton-pump inhibitors (PPI) due to pharmacodynamic interactions. Indeed, clopidogrel is a pro-drug needing to be activated, and this could be potentially affected by PPI. This is a relevant topic given that many patients treated with DAPT commonly receive also a PPI to prevent gastrointestinal complications (ulceration and bleeding) or due to pre-existing gastric disease. Some studies demonstrated that the use of a PPI, mainly omeprazole, was associated with an increased risk of cardiovascular adverse events, indeed the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) discouraged the concomitant use of omeprazole and clopidogrel. On the contrary, some other studies did not confirm this finding.

We performed a detailed analysis of the impact of PPI therapy on the 2-year clinical outcomes of 1970 patients undergoing PCI with stent implantation enrolled in the PRODIGY trial (a randomized trial comparing 2 DAPT regimens: 6-month versus 24-month DAPT).

In our study population, 738 patients (38%) were treated with a PPI (lansoprazole 90%) concomitantly to DAPT. We found that the ischemic and bleeding events at 2 years of follow-up were similar in patients treated with or without a PPI, irrespective of DAPT duration (6-month or 24-month). These findings support the concept that the concomitant use of PPI, when clinically indicated, in patients receiving clopidogrel is not associated with adverse clinical outcomes. What should clinicians and patients take away from your report?

Dr. Gargiulo: The take-home message of our analysis is that clinicians should not be afraid to prescribe Lansoprazole in patients treated with PCI and DAPT, particularly those patients with pre-existing gastrointestinal disease or at increased risk for gastrointestinal bleeding who can significantly benefit from PPI therapy. However, our findings do not apply to other types of PPI. What recommendations do you have for future research as a result of this study?

Dr. Gargiulo: Future studies should try to limit confounding factors. Our study has some limitations, as well as the majority of those studies that previously analyzed this issue and that provided contrasting evidence which generated concerns and uncertainties. Certainly the study was not designed to specifically explore the effects of PPI therapy and its prescription was left to the physician’s discretion. Furthermore, future research should investigate on: 1) potential differences among different types and dosages of PPI used; 2) the specific role of PPI therapy on gastrointestinal bleeding; 3) the potential different impact of PPI therapy in specific sub-groups of patients, such those with a predisposition for reduced clopidogrel responsiveness at genetic analysis. Is there anything else you would like to add?

Dr. Gargiulo: DAPT therapy aims to prevent ischemic events, however, it is associated to increased risk of bleeding. Gastrointestinal bleeding events are not so rare and could be harmful for patients as well as could need DAPT interruption, thus exposing them to an increased risk of thrombotic complications. In this delicate balance between ischemic and bleeding risk, the PPI therapy could be useful and could be prescribed safely. Thank you for your contribution to the community.


Impact of proton pump inhibitors on clinical outcomes in patients treated with a 6- or 24-month dual-antiplatelet therapy duration: Insights from the PROlonging Dual-antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY trial

Giuseppe Gargiulo, Francesco Costa, Sara Ariotti, Simone Biscaglia, Gianluca Campo, Giovanni Esposito, Sergio Leonardi, Pascal Vranckx, Stephan Windecker, Marco Valgimigli.

American Heart Journal, Vol. 174, p95–102
Published online: January 25 2016

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