The SPAF trial: Warfarin and aspirin reduce the risk of stroke in atrial fibrillation [Classics Series]

1. Patients with atrial fibrillation are at higher risk of ischemic stroke and systemic embolism.

2. Compared to placebo, warfarin and aspirin significantly reduced the risk of ischemic stroke and systemic embolism in patients with atrial fibrillation.

3. Today, antithrombotic therapy remains a vital consideration in managing patients with atrial fibrillation, though many more agents are available.

Original Date of Publication: August 1991

Study Rundown: Patients with atrial fibrillation have a higher risk of ischemic stroke. It is suspected that atrial fibrillation increases the risk of left atrial thrombi, which subsequently increases the risk of cardioembolic stroke. Thus, many patients with atrial fibrillation are treated with antithrombotic therapy to reduce the risk of stroke and systemic embolism. The Stroke Prevention in Atrial Fibrillation (SPAF) trial was conducted to determine the effects of warfarin and aspirin on ischemic stroke and systemic embolism as compared to placebo. While preliminary results had been published previously, this paper described the final results of the trial.

In summary, it was found that both warfarin and aspirin significantly reduced the risk of ischemic stroke and systemic embolism when compared with placebo. Patients on warfarin experienced a 67% reduction in this risk, while those on aspirin experienced a 42% reduction compared to patients taking placebo. Both warfarin and aspirin were compared directly to placebo, but not to one another. This study was one of the first randomized trials demonstrating that antithrombotic therapy reduced the risk of ischemic stroke and systemic embolism in patients with atrial fibrillation, and antithrombotic therapy remains a vital consideration in the management of these patients today.

Click to read the study in Circulation

In-Depth [randomized controlled trial]: This randomized trial was conducted at 15 centers. Inclusion criteria were electrocardiographically documented atrial fibrillation in the 12 months prior to enrollment, no prosthetic heart valves, no echocardiographic evidence of mitral stenosis, and no other requirements for or contraindications to aspirin or warfarin. Patients who had experienced a stroke or transient ischemic attack >2 years before enrollment were also eligible. Exclusion criteria included transient, self-limited atrial fibrillation episodes, prosthetic heart valves, stroke or TIA within the preceeding 2 years, life expectancy <2 years due to another medical condition (e.g., metastatic cancer), and chronic renal failure. Included patients were randomized to treatment with warfarin (dose-adjusted to international normalized ratio between 2.0 and 4.5), aspirin 325 mg daily, or placebo. The primary outcome was ischemic stroke or systemic embolism, while secondary outcomes were myocardial infarction, TIA, unstable angina requiring hospitalization, and death.

A total of 1330 patients were randomized. When compared to placebo, patients in the warfarin group experienced significantly lower rates of ischemic stroke and systemic embolism (2.3% vs. 7.4% per year; risk reduction 67%, 95%CI 27 to 85%, p = 0.01). Patients taking aspirin also experienced significantly lower rates of ischemic stroke and systemic embolism when compared with those on placebo (3.6% vs. 6.3% per year; risk reduction 42%, 95%CI 9 to 63%, p = 0.02). The rate of major bleeding was between 1 to 2% per year in the warfarin and aspirin groups.

Image: PD

©2015 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.