ACTIVE A
Trial question
What is the effect of clopidogrel addition to aspirin in patients with AF for whom vitamin K-antagonist therapy was unsuitable?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
42.0% female
58.0% male
N = 7554
7554 patients (3157 female, 4397 male)
Inclusion criteria: patients with AF who had an increased risk of stroke and for whom vitamin K-antagonist therapy was unsuitable
Key exclusion criteria: requirement of a VKA or clopidogrel, documented peptic ulcer disease within the previous 6 months, history of intracerebral hemorrhage, significant thrombocytopenia (platelet count < 50×10⁹/L), or ongoing alcohol abuse
Interventions
N=3772 clopidogrel (at a dose of 75 mg once daily plus aspirin 75-100 mg/day)
N=3782 placebo (matching placebo once daily plus aspirin 75-100 mg/day)
Primary outcome
Incidence of stroke, myocardial infarction, non-central nervous system systemic embolism, or death from vascular causes, at a median of 3.6 years of follow-up
6.8
7.6
7.6 % / y
5.7 % / y
3.8 % / y
1.9 % / y
0.0 % / y
Clopidogrel
Placebo
Significant decrease ▼
Significant decrease in the incidence of stroke, myocardial infarction, non-CNS systemic embolism, or death from vascular causes, at a median of 3.6 years of follow-up (6.8% / y vs. 7.6% / y; RR 0.89, 95% CI 0.81 to 0.98)
Secondary outcomes
Significant decrease in the incidence of stroke (2.4% / y vs. 3.3% / y; RR 0.72, 95% CI 0.62 to 0.83)
No significant difference in the incidence of myocardial infarction (0.7% / y vs. 0.9% / y; RR 0.78, 95% CI 0.59 to 1.03)
Safety outcomes
Significant differences in major bleeding (2.0% vs. 1.3%, p < 0.001; RR 1.57, 95% CI 1.29-1.92).
Conclusion
In patients with AF who had an increased risk of stroke and for whom vitamin K-antagonist therapy was unsuitable, clopidogrel was superior to placebo with respect to the incidence of stroke, myocardial infarction, non-CNS systemic embolism, or death from vascular causes, at a median of 3.6 years of follow-up.
Reference
ACTIVE Investigators, Connolly SJ, Pogue J et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med. 2009 May 14;360(20):2066-78.
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