This article is more than 5 years old. Information may no longer be current.
Current-OASIS 7 results prompt discussion of proper role of double dose of clopidogrel
Some see a double dose clopidogrel potentially becoming part of future guideline recommendations.
Click Here to Manage Email Alerts
A double dose of clopidogrel, combined with a high dose of aspirin, may yield greater benefits for some patients with acute coronary syndromes undergoing percutaneous coronary intervention than a standard dose, according to an analysis of the Current-OASIS 7 trial results.
The results may not be enough to change practice, but could have an effect on practice via guideline recommendations when taken in totality with other trial results, according to Robert A. Harrington, MD, a cardiologist at the Duke University Medical Center in Durham, N.C.
“Clopidogrel has a long and extensive clinical experience, and there are a number of areas where clopidogrel has gotten a class I guideline recommendation, so it has really become a cornerstone of what we do,” Harrington said in a presentation at Cardiovascular Research Technologies 2010 in Washington, D.C. “People who have studied clopidogrel responsiveness, however, note that it also has a number of well-known limitations. Its rapidity of onset, its predictability and its variability of effect have all been called into question in a variety of clinical studies. Some of this has to do with genetic and drug interactions.”
The Current-OASIS 7 trial included 25,087 patients with acute coronary syndromes who were then randomly assigned to receive either a double dose of clopidogrel (Plavix, Sanofi-Aventis/Bristol-Meyers Squibb) or a standard dose plus high- or low- dose aspirin before receiving percutaneous coronary intervention (n=17,232) or no percutaneous coronary intervention (n=7,855). Primary efficacy outcomes for the study were cardiovascular death, myocardial infarction or stroke at 30 days.
The researchers reported that patients undergoing percutaneous coronary intervention in the high-dose aspirin group who received a double dose of clopidogrel had better efficacy outcomes than those with standard doses of clopidogrel and lower doses of aspirin.
Patients in the double dose group had a reduced risk for cardiovascular death, MI or stroke (HR=0.85; 95% CI, 0.74) and lower risk for definite stent thrombosis (HR=0.58; 95% CI, 0.42-0.79).
There was also an increase in study-defined major (P=.006) and severe bleeding (P=.034) in patients receiving the double dose of clopidogrel. The double dose of clopidogrel was also more effective in the prevention of the primary study outcome in patients undergoing percutaneous coronary intervention who presented with both STEMI (5% vs. 4.2%, n=10,886) and unstable angina/non-STEMI (n=6,346) vs. those receiving the standard dose.
Although the results have not prompted revisions of current recommendations guiding the use of clopidogrel, some said the results of the Current-OASIS 7 trial and other studies may support a re-examination of current clopidogrel dosing recommendations in some patient populations.
“There is some equipoise here when you consider the totality of the biochemical data, the small trial data and the large trial data,” Harrington concluded. “With regard to the clinical recommendations, I think the higher dose will make it into the next version of the guidelines and may end up somewhere between a class IIa and class IIb recommendation.”
Although Harrington said potential changes in the guidelines may alter practice, there were many unanswered clinical questions that needed addressing before definitive changes in practice could be recommended or implemented.
“It is fair to say that the guideline writers are going to have a little bit of a challenge because the evidence is not Level A due to the many complexities and flaws in the data,” Harrington said. “I do believe that we should consider changing our practice, but I do not believe the question has been definitively answered.” – by Eric Raible
Harrington R. Should we change the clopidogrel dose following Current-OASIS 7. Presented at: Cardiovascular Research Technologies; Feb. 21-23, 2010; Washington.