SCAI: Evidence of interaction between proton pump inhibitors, clopidogrel not sufficient to change practice

Patients advised to continue their medication regimens and consult with their doctors.

Issue: January 2009

Conflicting data from two studies of clopidogrel and proton pump inhibitors prompted one professional society to issue a statement clarifying the implications.

According to a statement released by the Society for Cardiovascular Angiography and Interventions (SCAI), conflicting results from two studies presented at the American Heart Association Scientific Sessions 2008 in New Orleans raised questions about a potential interaction between clopidogrel (Plavix; Sanofi-Aventis, Bristol-Myers Squibb) and proton pump inhibitors in patients undergoing interventional procedures. The data were not sufficient to change clinical practice, according to the statement.

One of the studies was a retrospective cohort study of 14,383 patients receiving clopidogrel at the time of stent placement in which the researchers compared those who received clopidogrel alone (n=9,862) with those who received clopidogrel with a proton pump inhibitor (n=4,521). The researchers reported that patients receiving both proton pump inhibitors and clopidogrel had a higher incidence of a major CV event within one year vs. those patients not receiving proton pump inhibitors (32.5% vs. 21.5%; OR=1.79; 95% CI, 1.62-1.97). However, results from an analysis of ex vivo data from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial suggested that clopidogrel reduced adverse events in patients at one year to an approximately similar degree whether or not patients had been given proton pump inhibitors.

According to the statement from SCAI, patients were advised to remain on their medication regimens and to only change them if recommended to do so by their doctors.

“Retrospective studies, because of their design and because of patient variability in response, really do not have suitable substance for answering a question,” Stephen R. Bailey, MD, professor of medicine and radiology at the University of Texas Sciences Center in San Antonio and president-elect of SCAI, told Cardiology Today. “There are [researchers of] other studies who look specifically and prospectively at the use of clopidogrel and did not find the same interaction, so as a clinician, I currently would not change our standard of care.” – by Eric Raible

For more information:

Dunn S. #3999.
Aubert R. #3998.
Both presented at: American Heart Association Scientific Sessions; Nov. 8-12,2008; New Orleans.

Doctors should always be vigilant for the possibility of drug interactions. At the recent AHA meeting, two abstracts were presented that reached different conclusions. The first, from a claims database, found an increased risk for ischemic events in patients receiving both clopidogrel and proton pump inhibitors. The second, a post hoc analysis of data from a randomized clinical trial, found no evidence of an adverse interaction. Thus, at this point in time, the data do not support any change in clinical practice. A large randomized clinical trial called Clopidogrel and the Optimization of Gastrointestinal Events (COGENT-1) is ongoing and should help further clarify the role of proton pump inhibitors in patients receiving dual antiplatelet therapy.

– Deepak L. Bhatt, MD
Cardiology Today Editorial Board member

The problem with the combination of aspirin, clopidogrel and proton pump inhibitors is that we simply do not know whether there is interaction that increases the risk for coronary events. Recent attempts to answer this have provided diametrically opposed conclusions, further contributing to the confusion. Those conflicting reports originated from a database analysis and a secondary trial analysis — both not ideal avenues for answering the question. For now the safest strategy for patients is to continue their present regimens recommended by their physicians. To assume that one or the other conclusion is correct is premature and potentially harmful. Clopidogrel and aspirin carry an increased risk for gastrointestinal bleeding, and discontinuing a proton pump inhibitor may increase the risk for bleeding. The ongoing COGENT-1 trial will hopefully clarify this issue in a randomized trial of aspirin/clopidogrel and placebo vs. aspirin/clopidogrel and omeprazole and give us the answer we need. Finally, remember that proton pump inhibitors are not the only medications that diminish the gastrointestinal irritability.

– Peter C. Block, MD
Cardiology Today Section Editor