NEW YORK (Reuters Health) – Patients with an acute coronary syndrome referred for invasive treatment have similar outcomes whether they are given double-dose or standard-dose clopidogrel plus higher-dose or lower-dose aspirin, according to the results of a multicenter trial reported in the New England Journal of Medicine for September 2.

Dr. Shamir R. Mehta of McMaster University and Hamilton Health Sciences, Ontario, Canada and colleagues note that dual antiplatelet therapy with clopidogrel and aspirin is widely used in ACS patients, but optimal dosing hasn’t been established.

The researcher first randomized 25,086 patients with an ST-segment elevation MI or non-STE ACS to either double-dose or standard-dose clopidogrel, i.e., a 600-mg loading dose on day 1, followed by 150 mg/d for 6 days and 75 mg/d thereafter, or a 300-mg loading dose and 75 mg/d thereafter. The subjects were further randomized to concomitant treatment with either 300-325 mg/d aspirin (higher dose) or 75-100 mg/d (lower dose).

The primary outcome of cardiovascular death, myocardial infarction, or stroke at 30 days “occurred in 4.2% of patients assigned to double-dose clopidogrel as compared with 4.4% assigned to standard-dose clopidogrel (hazard ratio, 0.94; p=0.30),” the investigators report.

There was also no significant difference in primary outcome among those assigned to higher-dose aspirin (4.2%) or lower-dose aspirin (4.4%), for a hazard ratio of 0.97 (p=0.61)

Rates of major bleeding were significantly higher in the double-dose clopidogrel group versus the standard-dose group (2.5% vs. 2.0%, HR 1.24; p=0.01), but not between the higher-dose aspirin group and the lower-dose group, with rates of 2.3% in both.

As for any interaction between clopidogrel and aspirin dosing, the only statistically significant effect was seen in patients assigned to higher-dose aspirin, where the primary outcome occurred in 3.8% of those on double-dose clopidogrel versus 4.6% of the patients on standard-dose clopidogrel (p=0.03). However, this was unexpected and the team suggests it could have been a chance occurrence.

The study was funded by Sanofi-Aventis and Bristol-Myers Squibb.

N Engl J Med 2010; 363:930-942.