(a) ACTIVE Steering Committee
(b) ACTIVE Writing Group
(c) ACTIVE Investigators

(a) Rationale and design of ACTIVE: The atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events
(b) Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial
(c) Effect of clopidogrel added to aspirin in patients with atrial fibrillation

(a) Am Heart J 2006;151:1187–93
(b) Lancet 2006;367:1903–12
(c) N Engl J Med 2009;360:2066–78

Atrial fibrillation, stroke

To show noninferiority of clopidogrel plus ASA to oral anticoagulation (ACTIVE W), to compare the effect of clopidogrel plus ASA vs placebo when vitamin K therapy contraindicated (ACTIVE A), and to compare the effect of irbesartan vs placebo in addition to the regimens in ACTIVE W and ACTIVE A (ACTIVE I) in reducing vascular events in patients with atrial fibrillation at risk for stroke

ACTIVE W: open
ACTIVE A: randomised, double-blind, placebo-controlled
ACTIVE I: randomised, double-blind, placebo-controlled, partial-factorial

Aim 3 years

ACTIVE W: 6706 patients (3335 clopidogrel plus ASA, 3371 oral anticoagulation), mean age 70.2 years
ACTIVE A: 7554 patients (3772 clopidogrel plus ASA, 3782 ASA), mean age 71 years
ACTIVE I: aim 9000 patients

ACTIVE W: clopidogrel, 75 mg/day, plus ASA, 75–100 mg/day, or oral anticoagulation to target international normalised ratio 2.0–3.0
ACTIVE A: clopidogrel, 75 mg/day plus ASA, 75–100 mg/day, or placebo
ACTIVE I: as for ACTIVE W or ACTIVE A, plus irbesartan, 150 mg/day titrated to 300 mg/day, or placebo

In ACTIVE W, there were 234 primary outcome events of stroke, non-cerebral systemic embolism, MI and vascular death in the clopidogrel plus ASA group compared to 164 in the anticoagulation group. Annual risk was 5.60% in the clopidogrel plus ASA group compared to 3.90% in the anticoagulation group (relative risk 1.44, 95% CI 1.18–1.76; p = 0.0003). In ACTIVE A, major vascular events occurred in 832 patients receiving clopidogrel and in 924 patients receiving placebo (6.8% per year vs 7.6% per year, relative risk 0.89, 95% CI 0.81–0.98; p = 0.01). Reduction in risk of major vascular events in the clopidogrel group was primarily due to a reduction in the incidence of stroke, which occurred in 296 patients receiving clopidogrel and 408 patients receiving placebo (2.4% per year vs 3.3% per year, relative risk 0.72, 95% CI 0.62–0.83; p < 0.001). ACTIVE I is ongoing. Results not yet available

ACTIVE W was stopped early because of clear evidence of superiority of oral anticoagulation therapy