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(Circulation. 2008;117:192-199.)
© 2008 American Heart Association, Inc.

Health Services and Outcomes Research

Initial Aspirin Dose and Outcome Among ST-Elevation Myocardial Infarction Patients Treated With Fibrinolytic Therapy

Jeffrey S. Berger, MD, MS; Amanda Stebbins, MS; Christopher B. Granger, MD; Eric M. Ohman, MD; Paul W. Armstrong, MD; Frans Van de Werf, MD, PhD; Harvey D. White, DSc; R. John Simes, MD; Robert A. Harrington, MD; Robert M. Califf, MD; Eric D. Peterson, MD, MPH

From Duke Clinical Research Institute, Durham, NC (J.S.B., A.S., C.B.G., E.M.O., R.A.H., R.M.C., E.D.P.); University of Alberta, Edmonton, Alberta, Canada (P.W.A.); Gasthuisberg University Hospital, Leuven, Belgium (F.V.d.W.); Auckland City Hospital, Auckland, New Zealand (H.D.W.); and University of Sydney, Sydney, Australia (R.J.S.).

Correspondence to Jeffrey S. Berger, MD, MS, Department of Cardiovascular Medicine, Duke University Medical Center, PO Box 31007, Durham, NC 27710. E-mail berge026{at}mc.duke.edu

Received July 31, 2007; accepted October 19, 2007.

Background— Although treatment with immediate aspirin reduces morbidity and mortality in ST-elevation myocardial infarction, the optimal dose is unclear. We therefore compared the acute mortality and bleeding risks associated with the initial use of 162 versus 325 mg aspirin in fibrinolytic-treated ST-elevation myocardial infarction patients.

Methods and Results— Using combined data from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO I) and Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO III) trials (n=48 422 ST-elevation myocardial infarction patients), we compared the association between initial aspirin dose of 162 versus 325 mg and 24-hour and 7-day mortality, as well as rates of in-hospital moderate/severe bleeding. Results were adjusted for previously identified mortality and bleeding risk factors. Overall, 24.4% of patients (n=11 828) received an initial aspirin dose of 325 mg, and 75.6% (n=36 594) received 162 mg. The 24-hour mortality rates were 2.9% versus 2.8% (P=0.894) for those receiving an initial aspirin dose of 325 versus 162 mg. Mortality rates at 7 and 30 days were 5.2% versus 4.9% (P=0.118) and 7.1% versus 6.5% (P=0.017) among patients receiving the 325 versus 162 mg aspirin. After adjustment, aspirin dose was not associated with 24-hour (odds ratio [OR], 1.01; 95% CI, 0.82 to 1.25), 7-day (OR, 1.00; 95% CI, 0.87 to 1.17), or 30-day (OR, 0.99; 95% CI, 0.87 to 1.12) mortality rates. No significant difference was noted for myocardial infarction or the composite of death or myocardial infarction between groups. In-hospital moderate/severe bleeding occurred in 9.3% of those treated with 325 mg versus 12.2% among those receiving 162 mg (P<0.001). After adjustment, 325 mg was associated with a significant increase in moderate/severe bleeding (OR, 1.14; 95% CI, 1.05 to 1.24; P=0.003).

Conclusion— These data suggest that an initial dose of 162 mg aspirin may be as effective as and perhaps safer than 325 mg for the acute treatment of ST-elevation myocardial infarction.

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