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Shamir Mehta: “Double dose clopidogrel significantly reduced
stent thrombosis and major cardiovascular events in the PCI
population.”
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“Virtually every interventional cardiologist is using clopidogrel,” said Mehta at a press conference yesterday. “Tomorrow, after the results of this trial are presented, they’ll have to decide what to do. It’s a simple change to institute. It’s going from one pill to two pills a day, the cost implications are virtually negligible, and the benefits are large. This simple manoeuvre could improve patient outcomes in PCI.”
He said that the trial was the largest conducted so far in ACS and he predicted it would have an impact: “It will likely get recognition from guideline committees in some way.”
The phase III trial enrolled 25,087 ACS patients scheduled for early PCI. It compared double dose clopidogrel (600 mg, followed by 150 mg/day for one week, and then 75 mg/day) with the standard dose (300 mg followed by 75 mg/day). In a 2x2 factorial randomised design, it also compared high dose (300-325 mg/day) with low dose aspirin (75-100 mg/day).
Across the whole study group, double dose clopidogrel was associated with a nonsignificant 5% reduction in the primary composite endpoint of cardiovascular death, MI 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, others stopped the drugs early for CABG.
In the PCI group, which Mehta stressed was the intended patient population, there was a significant 15% relative reduction (95% 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 MI (95% CI 0.64- 0.95). There was also highly significant 42% reduction in the relative risk of definite stent thrombosis (a secondary endpoint) in the PCI group receiving the higher dose clopidogrel (HR 0.58, P=0.001).
When results were analysed according to the aspirin dose received, Mehta said that “perhaps the most surprising and informative finding” is that there was no difference in bleeding between the two doses.
Further analysis of the data suggested that the group on 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,” he said.
The conclusions from the trial were simple, he said: “” But for patients not undergoing PCI, the increased dose made no significant difference.
Summing up, Mehta said that, at McMaster “our interventional practice based on this trial will likely switch to higher doses of aspirin together with high dose clopidogrel”.