Maintenance on low-dose aspirin—rather than on higher doses—appears to be the best approach for patients with ST-segment elevation MI (STEMI) undergoing primary percutaneous coronary intervention (PCI), a post hoc analysis of the HORIZONS-AMI trial showed.

In a propensity score-adjusted analysis, high-dose aspirin (more than 200 mg/day) was associated with a significantly higher rate of major bleeding not related to CABG (6.5% versus 1.6%; HR 2.80, 95% CI 1.31 to 5.99), according to Roxana Mehran, MD, of Mount Sinai Medical Center in New York City, and colleagues.

There was no difference based on the dose of aspirin, however, in ischemic events, the researchers reported in the December issue of JACC: Cardiovascular Interventions.

The findings, they said, are supported by most - but not all - previous studies.

“Therefore,” they wrote, “this analysis contributes to an increasing literature that suggests that patients with acute coronary syndromes (both STEMI and non-STEMI) and those undergoing PCI should be maintained on low-dose rather than high-dose aspirin.” But, they added, “only a large-scale, randomized trial can definitively address this issue.” Based on the somewhat conflicting study results in this area, the 2011 consensus guidelines for PCI from the American College of Cardiology, American Heart Association, and Society for Cardiovascular Angiography and Interventions included a new class IIa recommendation stating that it is reasonable to use 81 mg/day maintenance aspirin instead of higher doses. Mehran and colleagues examined data from the HORIZONS-AMI trial, which included patients with STEMI who were undergoing primary PCI. The patients were first randomized to either bivalirudin (Angiomax) or unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor. After diagnostic coronary angiography, the patients were randomized again to either the Taxus Express paclitaxel-eluting stent or the Express bare-metal stent. All patients were given a loading dose of aspirin in the emergency department—either 324 mg chewable or 500 mg intravenously. While in the hospital, they received a daily dose of 300 to 325 mg. They were discharged with an indefinite aspirin maintenance dose of at least 75 mg/day. The patients also received clopidogrel loading dose of 300 or 600 mg followed by 75 mg daily for at least 6 months. The current analysis included 2,851 patients—80.3% who were discharged on 200 mg/day aspirin or less and 19.7% who were discharged on higher doses. Compared with those receiving low-dose aspirin, those who received the higher doses of aspirin were more likely to have a history of hypertension, hyperlipidemia, a family history of premature coronary disease, prior treatment with PCI or CABG, and a U.S. enrollment site. Before accounting for those between-group differences, patients receiving high-dose aspirin had higher rates of major adverse cardiovascular events (23.8% versus 17.5%), reinfarction (8.6% versus 5.7%), ischemic target vessel revascularization (15.4% versus 11.3%), major bleeding not related to CABG (6.5% versus 1.6%), and definite or probable stent thrombosis (5.4% versus 3%) at 3 years (P<0.05 for all). After accounting for those differences in a multivariate analysis, however, only major bleeding not related to CABG remained significantly elevated in the patients receiving high-dose aspirin, a difference that became evident within the first 2 months after discharge. The duration of thienopyridine use in the two groups did not significantly affect the findings (P=0.63). The authors acknowledged some limitations of the analysis, including the potential for confounding from unmeasured factors and the post hoc design, which renders the findings exploratory and hypothesis-generating. In addition, there was a lack of information on changes in aspirin dose after discharge, use of enteric-coated formulations of aspirin, and use of nonsteroidal anti-inflammatory drugs.