SPINAF

Stroke Prevention In Non-rheumatic Atrial Fibrillation (1992)

Condition

Prevention of stroke in patients with non-rheumatic AF

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Objective

To investigate whether low-intensity anticoagulation with warfarin would reduce the risk of stroke associated with non-rheumatic AF

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Trial design

Randomized, double-blind, placebo-controlled phase III trial
Active treatment: low-dose warfarin (INR 1.2–1.5) (n=260 with no history of infarction; n=21 with previous stroke)
Control treatment: placebo (n=265 with no history of infarction; n=25 with previous stroke)

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Endpoints

Primary endpoint: cerebral infarction
Secondary endpoints: cerebral hemorrhage and death

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Trial participants

571 men (mean age 67 years) with chronic non-rheumatic AF, divided in 2 groups:

  • 525 patients with no history of stroke
  • 46 patients with previously cerebral infarction

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Results

Efficacy outcome: In patients with no history of stroke receiving warfarin, cerebral infarction occurred in 0.9% per year compared to 4.3% per year for the placebo group (relative risk reduction with warfarin 79%). A special benefit of warfarin was observed in patients aged >70 years (n=288). In this subgroup, the annual event rate was 0.9% with warfarin vs. 4.8% with placebo (relative risk reduction with warfarin 79%). Cerebral infarction was more common among patients with a history of stroke: 6.1% per year in the warfarin group compared to 9.3% per year in the placebo group (relative risk reduction with warfarin 40%). The only non-fatal cerebral hemorrhage occurred in a patient assigned to warfarin. Of the 525 patients without a previous cerebral infarction, 15 in the warfarin group and 22 in the placebo group died (3.3% vs. 5.0% per year, relative risk reduction with warfarin 31%)
Safety outcome: In patients with no history of cerebral infarction, major bleeding events were slightly more common in the warfarin group (1.3% vs. 0.9% per year). The incidence of minor hemorrhages was 14.0% per year with warfarin and 10.5% per year with placebo

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Summary

Efficacy: Low-intensity anticoagulation with warfarin reduces the incidence of cerebral infarction among patients with AF. This benefit extended to patients >70 years of age
Safety: With warfarin, there was no excess risk of major bleeding. Both major and minor hemorrhages were slightly more common in the warfarin group

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Reference

Ezekowitz MD, Bridgers SL, James KE, Carliner NH, Colling CL, Gornick CC, Krause-Steinrauf H, Kurtzke JF, Nazarian SM, Radford MJ. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. N Engl J Med 1992;327:1406-1412

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Corresponding author

Michael D. Ezekowitz, MD, Cardiovascular Section, 111B, Department of Veterans Affairs Medical Center, Clinical Campus, Yale University School of Medicine, 950 Campbell Ave., West Haven, CT 06516

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