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| |  Patients at Risk of Adverse Events Within 3 Months After Stopping Certain ACS Therapy CHICAGO, IL -- February 6, 2008 -- Patients who receive the antiplatelet medication clopidogrel after an acute coronary syndrome (such as heart attack) appear to be at greater risk of a heart attack or death in the 90 days after stopping clopidogrel treatment, according to a study in the February 6 issue of JAMA. Randomized trials have established the effectiveness of clopidogrel therapy following hospitalization for acute coronary syndrome (ACS) for patients treated either medically or with percutaneous coronary intervention (PCI). Current cardiology guidelines recommend clopidogrel therapy for up to 1 year for patients treated medically or with a bare metal stent. It is unknown whether there may be a rebound effect or concentration of thrombotic events shortly after stopping treatment with clopidogrel, as has been found for patients after long-term aspirin therapy, according to the researchers. P. Michael Ho, MD, PhD, of the Denver VA Medical Center, Denver, and colleagues assessed the incidence and timing of death or acute myocardial infarction (AMI; heart attack) after stopping treatment with clopidogrel in a group of 3,137 patients with ACS who were discharged from 127 Veterans Affairs hospitals. Average followup after discontinuation of clopidogrel was 196 days for patients treated medically with ACS without stents (n = 1,568) and 203 days for patients with ACS treated with PCI (n = 1,569). Further analysis indicated that the interval of days 0 to 90 was associated with nearly twice the risk of adverse events after stopping treatment with clopidogrel compared with the interval of days 91 to 180. Among the PCI-treated patients, average duration of clopidogrel treatment was 278 days. All-cause death (n = 68) or AMI (n = 56) occurred in 7.9% (n = 124) of the patients, with 58.9% (n = 73) of the events occurring during days 0 to 90, 23.4% (n = 29) occurring during days 91 to 180, and 6.5% (n = 8) occurring during days 181 to 270 after stopping clopidogrel. After adjustment for total duration of clopidogrel treatment following hospital discharge, the interval of days 0 to 90 after stopping clopidogrel was associated with an 82% increased risk of adverse events compared with the interval of days 91 to 180. The authors write that there is in vitro and physiological evidence to support a short-term increase in platelet activation and associated thrombotic risk immediately after stopping antiplatelet therapy. "There are several potential implications of this study. Even though the absolute event rates were low, the relative increase in adverse events in the early period after stopping treatment with clopidogrel was nearly 2-fold higher than later periods. In addition, the absolute number of adverse events attributable to this event clustering is significant when extrapolated to a population level, considering the number of patients admitted with ACS and discharged with posthospital treatment with clopidogrel therapy both in the United States and worldwide," the researchers say. "These findings, however, do not necessarily offset the benefits of clopidogrel therapy. Rather, additional studies are needed to confirm the presence of the event clustering after cessation of clopidogrel and to better understand the pathophysiology of this phenomenon. If these findings are subsequently confirmed, guideline recommendations may need to be reconsidered in terms of duration of clopidogrel therapy and perhaps the means of drug cessation," they conclude.
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SOURCE: JAMA and Archives Journals
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