News:Optimal does of aspirin following ST-elevation myocardial infarction

December 18, 2007 By Benjamin A. Olenchock, M.D. Ph.D. [mailto:bolenchock@partners.org]

As has been seen with all anti-platelet agents, the risk of bleeding is increased hand-in-hand with the effectiveness of platelet inhibition and prevention of ischemic events. This was highlighted recently by the TRITON-TIMI 38 trial: more consistent and effective platelet inhibition with prasugrel resulted in improvement in ischemic outcomes but increased major bleeds. The goal of the current analysis was to determine whether initial aspirin dose affected rates of ischemic events or significant bleeding.

The authors analyzed data from over 48,000 ST-elevation myocardial infarction (STEMI) patients from 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). Patients were divided into 2 groups based on initial aspirin dose (126-162 mg, n=36,594 and 163-330 mg, n=11,828). The choice of aspirin dose was not prescribed in the study protocols. Baseline characteristics were very similar between the two groups, although small differences were statistically significant due to the large sample size. Most patients (61%) in the low-dose aspirin group had subsequent in-hospital treatment with aspirin in the higher dose range.

In the adjusted analysis, there was no association between aspirin dose and risk of MI (OR 1.00, CI 0.87 to 1.15) or stroke (OR 1.14, CI 0.91 to 1.41) at 7 days. In the unadjusted analysis, there was higher 30-day mortality in the 325 mg aspirin group (7.1% vs. 6.5%), however this difference was not apparent after adjustments for covariates. The higher aspirin dose was associated with increased moderate or severe bleeding (OR 1.14, CI 1.05 to 1.24).

It would be interesting to know the reason why physicians chose a higher or lower aspirin dose, especially since most patients receiving 162 mg later received higher doses. More patients in the 162 mg dose group presented with inferior MIs, fewer had recent chest pain, and more were diabetic. Although the symptom to treatment time was similar between groups, it is possible that the decision to give a lower dose aspirin could be linked in some immeasurable way to outcome (i.e. selection bias is always a possibility). Nonetheless this is a very large, convincing study. The data suggest that 162 mg is as efficacious as 325 mg as a first-dose of aspirin in patients with STEMI. The risks of bleeding with aspirin are dose-dependent, so the lowest effective dose should be used. It is not clear how these data apply to patients treated with a thienopyridine or GPIIbIIIa inhibitor.

Jeffrey S. Berger, Amanda Stebbins, Christopher B. Granger, Eric M. Ohman, Paul W. Armstrong, Frans Van de Werf, Harvey D. White, R. John Simes, Robert A. Harrington, Robert M. Califf, and Eric D. Peterson. Initial Aspirin Dose and Outcome Among ST-Elevation Myocardial Infarction Patients Treated With Fibrinolytic Therapy. Circulation 2007: published online before print December 17, 2007, 10.1161/CIRCULATIONAHA.107.729558.