Following an acute coronary syndrome (ACS), patients who receive clopidogrel, aspirin and proton pump inhibitors (PPIs) to reduce the risk of gastrointestinal bleeding that may be associated with clopidogrel, may have an increased risk of subsequent hospitalization for ACS or death, according to a study in the March 4 issue of the Journal of the American Medical Association.
Recent studies have found that PPIs may reduce the effectiveness of clopidogrel (Plavix, Bristol-Myers Squibb and Sanofi-Aventis), but the clinical significance of the findings to patients is not clear, according to the authors.
P. Michael Ho, MD, PhD, of the Denver Veterans Affairs (VA) Medical Center, and colleagues evaluated the use of clopidogrel plus PPI following hospital discharge for ACS and compared rates of all-cause death and rehospitalization for ACS, between patients taking clopidogrel plus PPI versus clopidogrel without PPI. The study included patients from 127 VA hospitals. Vital status information was available for all patients through September 30, 2006.
Of 8,205 patients with ACS taking clopidogrel after hospital discharge, 5,244 patients were prescribed PPI at discharge or during follow-up. The researchers said that death or rehospitalization for ACS occurred in 29.8 percent of patients prescribed clopidogrel plus PPI and 20.8 percent of patients prescribed clopidogrel without PPI. Use of clopidogrel plus PPI at any point in time was associated with a 25 percent increased odds of death or rehospitalization for ACS compared with use of clopidogrel without PPI.
For the individual outcomes, investigators said that the rates of recurrent hospitalization for ACS (14.6 percent vs. 6.9 percent) and revascularization procedures (15.5 percent vs. 11.9 percent) were higher among patients taking clopidogrel plus PPI compared with those taking clopidogrel without PPI. However, the risk of death was similar between the two groups.
"When patients were not taking clopidogrel after hospital discharge, a prescription for PPI was not associated with death or rehospitalization for ACS, supporting the hypothesis that the interaction of PPI and clopidogrel, rather than PPI itself, was associated with increased adverse outcomes," the authors wrote.
The study "raises some concern about concomitant [accompanying] use of PPI medications and clopidogrel following hospitalization for ACS," the authors wrote. "While the risk estimates associated with clopidogrel plus PPI vs. clopidogrel without PPI were modest, the absolute number of adverse events attributable to this potential drug interaction is considerable when extrapolated to a population level, given how frequently PPI medications are prescribed to patients receiving dual-antiplatelet therapy."
In January, the FDA has notified healthcare professionals that Bristol-Myers and Sanofi agreed to conduct studies that will allow a better understanding and characterization of the effects of genetic factors and other drugs, especially PPIs, on the effectiveness of clopidogrel.
"Pending additional evidence, however, the results of this study may suggest that PPIs should be used for patients with a clear indication for the medication, such as history of gastrointestinal tract bleeding, consistent with current guideline recommendations, rather than routine prophylactic prescription," Ho and colleagues wrote. "Alternative gastrointestinal tract medication regimens also may be considered until additional data regarding concomitant use of PPI and clopidogrel becomes available."