ESC: TIMI study offers reassurance on concomitant use of PPIs and antiplatelets

An analysis of two TIMI trials, PRINCIPLE-TIMI 44 and TRITON-TIMI 38, has found no evidence to support the contention that concomitant PPI use diminishes the efficacy of either clopidogrel or prasugrel. The results  were presented today at the ESC and published simultaneously in the Lancet.

Michelle O’Donoghue and colleagues performed a multivariate analysis to assess the association of PPIs and clinical efficacy. Although PPIs did have a modest impact on the pharmacodynamics of the drugs they observed no difference in clinical efficacy. Their findings, they wrote, “do not support the need to avoid concomitant use of PPIs for gastric protection in patients receiving thienopyridine therapy who are at increased risk for gastrointestinal bleeding.”

In an accompanying comment in the Lancet, Dirk Sibbing and Adnan Kastrati ask “is the interaction of PPIs with thienopyridines fact of fiction?” Although the interaction “is a fact in terms of pharmacodynamics,” they argue, when it comes to clinical impact the interaction “seems to be a fiction for most patients with a risk profile similar to that of patients enrolled in the TRITON-TIMI 38 trial.” For high-risk patients, however, more caution is needed, they write.

At the ESC, the designated discussant, Kurt Huber, expressed skepticism that the study had resolved the complex issue of PPI and thienopyridine interactions. “Only a prospective randomized trial of PPI use will be capable of establishing the safety of PPIs in combination with thienopyridines.”

Here is the Lancet press release:

PROTON PUMP INHIBITORS DO NOT INTERFERE WITH BENEFIT OF ANTIPLATELET DRUGS CLOPIDOGREL OR PRASUGREL IN PATIENTS AFTER AN ACUTE CORONARY SYNDROME (Embargo 1830H New York time Monday 31 August 2009)

Proton pump inhibitors (PPIs—a commonly prescribed antacid medication) do not interfere with the clinical benefit of the anticlotting drugs clopidogrel or prasugrel (thienopyridines) in patients after an acute coronary syndrome (heart attack or unstable angina). These findings are in contrast to other recent studies that have shown potential harm when these two classes of drugs are combined. The results are published in an Article Online First and in an upcoming edition of The Lancet, written by Dr Michelle O’Donoghue, Brigham and Women’s Hospital, Boston, MA, USA, and colleagues.

PPIs are often administered with clopidogrel and prasugrel, to help reduce the risk of gastrointestinal bleeding, a strategy that is endorsed by existing guidelines. But several studies have raised concerns that PPIs could negate the clinical benefit of clopidogrel. The authors studied the effects of PPIs in the TRITON-TIMI 38 trial, and one other, smaller trial. TRITON-TIMI 38 enrolled 13608 patients after a heart attack or unstable angina and randomly assigned them to clopidogrel or prasugrel. Use of a PPI in combination with these drugs did not increase the risk of cardiovascular events, including death, heart attack, or stroke.

The authors conclude: “The current findings do not support the need to avoid concomitant use of proton pump inhibitors, when clinically indicated, in patients receiving clopidogrel or prasugrel.”

In an accompanying Comment, Dr Dirk Sibbing and Dr Adnan Kastrati, Technische Universität München, Munich, Germany, agree that patients with a risk profile similar to those patients in the TRITON-TIMI 38 study can be safely treated with a proton pump inhibitor on top of clopidogrel or prasugrel. They say: “Caution is however required when prescribing proton pump inhibitors in selected high risk patients with intrinsic reduced response to thienopyridines.”

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