CURRENT-OASIS 7 overall: outcomes same with high-, low-dose clopidogrel
Last Updated: 2010-09-01 18:26:20 -0400 (Reuters Health)
By Robert Saunders
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 online today in the New England Journal of Medicine for September 2.
The primary outcome of the CURRENT-OASIS 7 trial was the time to cardiovascular death, myocardial infarction, or stroke up to day 30 - and there was no difference between the groups.
But lead author Dr. Shamir R. Mehta of McMaster University and Hamilton Health Sciences, Ontario, Canada told Reuters Health by email that the overall cohort of more than 25,000 patients included those who ultimately didn't undergo percutaneous interventions. Another analysis that will be reported online this evening, and which will appear in print tomorrow in The Lancet, covered the patients who actually underwent PCI. (That paper is reported in a separate article today by Reuters.)
"The Lancet paper demonstrated that a double-dose regimen of clopidogrel was superior to the standard dose in preventing major cardiovascular events and stent thrombosis in patients undergoing PCI," Dr. Mehta said. "It suggests that all ACS patients managed with intended early PCI should be considered for the double-dose regimen."
In the overall population, he added, about one-third did not have significant CAD or stopped antiplatelet treatment because they required CABG or were not candidates for revascularization. This group would not derive any advantage from a high-dose regimen and "likely diluted the benefit in the PCI patients."
"Taken together the message is very simple," Dr. Mehta said. "We recommend that patients undergoing PCI receive the full double-dose regimen of clopidogrel and those who do not have PCI should be treated with the standard-dose regimen of clopidogrel."
For CURRENT-OASIS 7, he and his colleagues 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., either 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.
The study was funded by Sanofi-Aventis and Bristol-Myers Squibb.
SOURCE:http://link.reuters.com/mav78n
N Engl J Med 2010; 363:930-942.
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