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ACG, ACC, AHA release joint statement regarding ongoing exploration of safety of PPIs in combination with clopidogrel

Friday, November 14 2008 | Comments

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What's This? The American College of Gastroenterology (ACG), American College of Cardiology (ACC), and American Heart Association (AHA) released a joint statement advising that patients being treated concomitantly with proton pump inhibitors (PPIs) and clopidogrel should not change their drug regimen because of concerns regarding the possibility of diminished platelet inhibition, despite conflicting data from recent studies that may suggest otherwise.

The statement comes on the heels of new data from a pair of studies presented at the AHA's 2008 Scientific Sessions. The first study reviewed major adverse cardiovascular events, including hospitalization for stroke, myocardial infarction (MI), angina, or bypass surgery, during a 1-year period in 14,383 patients in the National Medco Integrated Database who received clopidogrel following stent placement and were >=80% compliant in refilling their prescribed treatment. Outcomes for the patients who received clopidogrel alone (n=9,862) were compared with outcomes for the patients who received clopidogrel along with PPIs (n=4,521).

According to the data, the patients who received concomitant PPI therapy had significantly more major adverse cardiovascular events during the study period than did the patients who received clopidogrel alone (incidence rate, 32.5% vs 21.2%, respectively; adjusted OR, 1.79).

However, the cardiovascular risk factor profile was worse for the patients who received concomitant PPI therapy, and the study included other limitations, including insufficient data regarding the participants' use of over-the-counter drugs and the presence of certain other cardiovascular risk factors, such as family history and smoking status. (Aubert RE, et al. Abstract 3998.)

In contrast, the second study found no increased risk among patients who received PPI therapy along with clopidogrel relative to those who received clopidogrel alone. Specifically, any use of a PPI drug was associated with a significant increase in the 28-day risk for a composite endpoint of death, MI, or urgent target vessel revascularization and in the 1-year risk for a composite endpoint of death, MI, or stroke, but "[c]lopidogrel reduced adverse events at 1 year to an approximately similar degree whether or not patients were on a PPI," the authors of the study wrote. (Dunn SP, et al. Abstract 3999.)

According to the ACG, ACC, and AHA statement, the ongoing COGENT-1 study--in which patients with coronary artery disease have been randomized to receive aspirin plus clopidogrel in combination with omeprazole 20 mg or placebo--should provide answers to some of the remaining questions regarding the safety of PPI therapy in patients who are also taking clopidogrel.

The joint statement noted that neither of the studies presented at the AHA conference "provides sufficient evidence to change clinical practice" and that other clinical trials need to be conducted to more fully evaluate this issue.

"This interaction has not been studied in large numbers of patients, so there is no definitive evidence that the use of PPIs will keep clopidogrel from working to prevent cardiac events," the organizations concluded.

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