Outcomes for Patients with Acute Coronary Syndromes Based on Clopidogrel or Aspirin Dose

A new randomized trial comparing doses of clopidogrel and aspirin in patients with acute coronary syndromes who had been referred for an invasive strategy found that there was no significant difference between a double-dose clopidogrel regimen and the standard dose regimen when measuring cardiovascular death, myocardial infarction, or stroke within 30 days. The results of the study were published in the New England Journal of Medicine [2010;363(10):930-942]. Clopidogrel and aspirin are medications that are often prescribed to patients with acute coronary syndromes; however, the ideal dosage of either medication is not clear. In the CURRENT-OASIS 7 (Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events –Seventh Organization to Assess Strategies in Ischemic Syndromes) trial, researchers investigated optimal doses of both medications by randomly assigning 25,086 patients using a 2-by-2 factorial design to either receive a 7-day, double dose of clopidogrel or a standard dose of clopidogrel, as well as either a higher dose of aspirin or lower dose of aspirin. Those patients assigned to the double dose of clopidogrel received 600 mg on the first day as a loading dose and 150 mg on days 2 through 7, followed by 75 mg daily on days 8 through 30, while those in the standard dose group received a loading dose of 300 mg and then 75 mg daily for the remainder of the study. All participants were given the same loading dose of aspirin (≥300 mg) before researchers divided the groups and gave those assigned to a higher dose of aspirin (300-325 mg daily on days 2-30), while giving the lower-dose group 75 to 100 mg daily during the same time period. The participants in the study were at least 18 years of age and had either a non–ST-segment elevation acute coronary syndrome or an ST-segment elevation myocardial infarction. To be included, they also had to have a coronary angiographic assessment and have a plan to undergo a percutaneous coronary intervention no later than 72 hours after randomization. Researchers identified the primary outcome of the study as the time to cardiovascular death, myocardial infarction, or stroke within 30 days. Secondary outcomes of the study were the individual components of the primary outcome, a composite of death from cardiovascular causes, myocardial infarction, stroke, or recurrent ischemia, or death from any cause. During the study, researchers found there was no significant difference in the primary outcome for patients taking either dose of clopidogrel. According to the results, 4.2% of those patients taking the double dose of clopidogrel experienced either cardiovascular death, myocardial infarction, or stroke by day 30, compared with 4.4% of the patients in the standard dose group (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.83-1.06; P=.30). In addition, researchers found no significant difference in the rate of death from any cause between the 2 groups. The study’s authors did note that major bleeding occurred in 2.5% of those patients taking a double dose of clopidogrel compared with 2.0% of patients on the standard dose (HR, 1.24; 95% CI, 1.05-1.46; P=.01); however, patients taking the double dose did not have a significant increase in fatal or intracranial bleeding. There was also no significant difference in the primary outcome for the aspirin groups. The study found that 4.2% of those patients on the higher dose of aspirin experienced the primary outcome within 30 days compared with 4.4% of those in the low-dose aspirin group (HR, 0.97; 95% CI, 0.86-1.09; P=.61). There was also no difference in major bleeding in the groups.