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| |  Clopidogrel Plus PPI Increase Risk of Death, Hospitalisation in Patients With ACS CHICAGO -- March 3, 2009 -- Patients who receive a proton pump inhibitor (PPI) with dual-antiplatelet therapy following an acute coronary syndrome (ACS) have an increased risk of subsequent hospitalisation for ACS or death, according to a study in the March 4 issue of the Journal of the American Medical Association. PPI medications are often prescribed at the start of treatment with clopidogrel and aspirin in patients with ACS with the goal of reducing the risk of gastrointestinal tract bleeding. However, recent studies have suggested that PPI medications may reduce the effectiveness of clopidogrel, but the clinical significance of these findings to patients is not clear. Therefore, P. Michael Ho, MD, Denver VA Medical Center, Denver, Colorado, and colleagues evaluated the use of clopidogrel plus PPI following hospital discharge for ACS and compared rates of all-cause death and rehospitalisation for ACS between patients taking clopidogrel plus PPI versus clopidogrel without PPI. The study included patients from 127 Veterans Affairs hospitals. Vital status information was available for all patients through September 30, 2006. Of 8,205 patients with ACS taking clopidogrel after hospital discharge, 63.9% (n = 5,244) were prescribed PPI at discharge or during follow-up. Death or rehospitalisation for ACS occurred in 29.8% of patients prescribed clopidogrel plus PPI and 20.8% of patients prescribed clopidogrel without PPI. Use of clopidogrel plus PPI at any point in time was associated with a 25% increased odds of death or rehospitalisation for ACS compared with use of clopidogrel without PPI. For the individual outcomes, the rates of recurrent hospitalisation for ACS (14.6% vs 6.9%) and revascularisation procedures (15.5% vs 11.9%) were higher among patients taking clopidogrel plus PPI compared with those taking clopidogrel alone. However, the risk of death was similar between the 2 groups. "When patients were not taking clopidogrel after hospital discharge, a prescription for PPI was not associated with death or rehospitalisation 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. "This study raises some concern about concomitant use of PPI medications and clopidogrel following hospitalisation for ACS. While the risk estimates associated with clopidogrel plus PPI versus 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." "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," the authors continued. "Alternative gastrointestinal tract medication regimens also may be considered until additional data regarding concomitant use of PPI and clopidogrel becomes available." SOURCE: Journal of the American Medical Association
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