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Abstract & Commentary
Synopsis: The dose of aspirin after discharge for acute coronary syndromes may affect the 6-month clinical course.
Source: Quinn MJ, et al. Aspirin dose and six-month outcome after an acute coronary syndrome. J Am Coll Cardiol. 2004;43:972-978.
The well-documented benefits of aspirin in a diverse spectrum of patients with atherosclerosis have been observed with a wide dose range (75-1500 mg). Although 75-325 mg is most frequent in the United States, little is known about the comparative efficacy in this dose range. Thus, Quinn and colleagues analyzed the GUSTO IIb and PURSUIT databases, which were large acute coronary syndrome (ACS) studies. GUSTO IIb included ST elevation ACS; PURSUIT did not. GUSTO IIb studied heparin vs hirudin and streptokinase vs tissue plasminogen activator in the ST elevation patients; aspirin therapy was at the discretion of the treating physician. PURSUIT studied eptifibatide vs placebo, and aspirin doses of 80-325 mg were recommended. In both studies, the initial aspirin dose was known, and in PURSUIT the discharge dose was also recorded. For this study, initial or discharge doses < 150 mg were compared to > 150 mg in 20,521 patients enrolled in these 2 studies (96% of the total study populations). The primary end points were death, myocardial infarction (MI), or stroke between hospital discharge and 6 months of follow-up. Low-dose aspirin (< 150 mg) was prescribed in 30%. Those receiving intermediate dose (> 150 mg) were younger, were often ST elevation MI, and generally sicker than the low-dose group. At 6 weeks, 1310 patients had a primary event, and there was no effect of aspirin dose on the frequency of the composite end point even after adjustment for the considerable imbalances between the 2 groups. However, intermediate-dose aspirin was associated with a reduction in 6-month MI rates (HR, .79; 95% CI, .64-.98; P = .03) but had a trend toward increased stroke rates (HR, 1.59; CI, .95-2.65; P = .08). In a highly matched subgroup of 8531 patients, the reduction in MI was no longer significant (HR, .83; CI, .66-1.05; P = .12) with intermediate-dose aspirin, but the increase in stroke was (HR, 1.74; CI, 1.01-3.02; P = .05). Quinn et al concluded that the dose of aspirin after discharge for acute coronary syndromes may affect the 6-month clinical course.
Comment by Michael H. Crawford, MD
This retrospective, observational analysis is the largest study to address the issue of aspirin dosage in ACS, and the results are counterintuitive and provocative. In the larger, unmatched, adjusted database, the intermediate dose reduced subsequent MI, but there was a trend toward increased stroke. In the smaller, but highly matched subgroup, there was no effect on subsequent MI, but stroke risk was almost doubled. Such results fly in the face of data showing that in up to 20% of ACS patients there is resistance to the effect of aspirin, which can be overcome with larger doses. These data suggest that any benefit from increased aspirin dosage is difficult to demonstrate and may be offset by increased stroke. No analysis of these data showed mortality benefits for higher aspirin dose. The results are consistent with 2 older, randomized, controlled studies of aspirin for primary prevention. The US Physician study showed reduced MI in physicians randomized to aspirin 325 mg/d but no gain in mortality due to increases in stroke rates. The British Physicians study of 500 or more mg aspirin a day showed no benefit on MI or mortality and a significantly higher stroke rate. In the late ’80s when those studies were released, there was much criticism of the studies (eg, British physicians smoked), etc. However, there has been a trend toward lower aspirin doses, and all 3 Western cardiology associations (EHA, AHA, ACC) recommend 75-325 mg/d for coronary artery disease patients. This analysis suggests that doses > 150 mg may be harmful. Clearly, the incidence of bleeding and GI toxicity is less with lower doses of aspirin in other studies. This study did not have such data. Also, whether the patients received aspirin and at what dose during follow-up is unknown. So any conclusions from this study must be tempered. In addition, the effect of aspirin may be different in different vascular beds. It is generally thought that ACS stimulates platelet activity and may require higher aspirin doses than peripheral vascular disease. Accordingly, what would be appropriate aspirin doses at this stage of our knowledge? I would recommend 150 mg/d for ACS in the hospital and 75 mg/d at discharge for the first 6 months. The appropriate dose beyond 6 months is unclear.