CURRENT OASIS 7 Study Supports Higher Clopidogrel Dose Before PCI

August 31, 2009—At the European Society of Cardiology (ESC) Congress in Barcelona, Spain, Shamir Mehta, MD, presented results from the CURRENT OASIS 7 (Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent Events/Optimal Antiplatelet Strategy for Interventions) trial that could mean adjustments to current guidelines. Dr. Mehta stated that the trial was the largest conducted so far in acute coronary syndrome, and he predicted it will likely be recognized by guideline committees in some way.

"Virtually every interventional cardiologist is using clopidogrel," commented Dr. Mehta. "After the results of this trial, they will have to decide what to do. It is a simple change to institute. It is going from one pill to two pills per day. The cost implications are virtually negligible, and the benefits are large. This simple maneuver could improve patient outcomes in PCI."

According to the ESC, the phase 3 trial enrolled 25,087 acute coronary syndrome patients scheduled for early PCI. It compared double-dose clopidogrel (600 mg, followed by 150 mg/day for 1 week and then 75 mg/day) with the standard dose (300 mg followed by 75 mg/day). In a 2 X 2 factorial randomized design, it also compared high-dose (300–325 mg/day) with low-dose aspirin (75–100 mg/day).

Across the entire study group, double-dose clopidogrel was associated with a nonsignificant 5% reduction in the primary composite endpoint of cardiovascular death, myocardial infarction, or stroke at day 30. However, only 70% of the study group (n = 17,232) received PCI; most of the remainder had no significant coronary artery disease, and others stopped the drugs early for CABG.

In the PCI group, which Dr. Mehta stressed was the intended patient population, there was a significant 15% relative reduction (95% confidence interval [CI], 0.74–0.99) in the composite endpoint in patients receiving the higher dose of clopidogrel. The major contributor was a 22% reduction in myocardial infarction (95% CI, 0.64–0.95). There was also a highly significant 42% reduction in the relative risk of definite stent thrombosis (a secondary endpoint) in the PCI group receiving the higher-dose clopidogrel (hazard ratio, 0.58; P = .001).

Dr. Mehta observed that when results were analyzed according to the aspirin dose received, perhaps the most surprising and informative finding was that there was no difference in bleeding between the two doses. Further analysis of the data suggested that the group on the higher-dose aspirin consistently did better for primary outcome and for the PCI group. "There was no downside to using the higher-dose aspirin, and there may have been a benefit," Dr. Mehta stated. But for patients not undergoing PCI, the increased dose made no significant difference. In summary, Dr. Mehta said that based on this trial, he and his colleagues at McMaster University will likely switch to higher doses of aspirin together with high-dose clopidogrel.