Stroke Prevention in Atrial Fibrillation Study - SPAF


Warfarin vs. aspirin for ischemic stroke in atrial fibrillation.


For the treatment of atrial fibrillation in the absence of rheumatic valvular disease, aspirin is a benefit in all eligible patients; warfarin is a benefit in those eligible patients who can take warfarin.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 1,330
Mean Follow Up: 1.3 years
Mean Patient Age: 67
Female: 29

Patient Populations:

Adults with ECG documentation of atrial fibrillation in the preceding 12 months without prosthetic heart valves, echocardiographic evidence of mitral stenosis, other requirements for or contraindication to aspirin or warfarin therapy.


Unable to obtain consent or follow-up.

Cardiac, e.g., transient, self-limited atrial fibrillation; successful electrical or chemical cardioversion with no recurrence; mitral stenosis by echocardiography; NYHA Class IV congestive heart failure, etc.

Noncardiac, e.g., stroke, transient ischemic attack, or carotid endarterectomy within previous 24 months (excluded because of the perceived need for antithrombotic therapy [i.e., unable to receive placebo] by the majority of study investigators at the time of study design); life expectancy <24 months because of other medical condition such as metastatic cancer; chronic renal failure; thrombocytopenia with less than 100,000 platelets/mm3 or anemia with hemoglobin concentration of less than 10 g/dL, etc.

Primary Endpoints:

Ischemic stroke or systemic embolism

Secondary Endpoints:

Death, myocardial infarction (MI), transient ischemic attack, or unstable angina requiring hospital admission.

Drug/Procedures Used:

Warfarin adjusted to prolong prothrombin time to create an international normalized ratio between 2.0 and 3.5; aspirin 325 mg/day; or both.

Principal Findings:

The rate of primary events in patients assigned to placebo was 6.3% per year and was reduced by 42% in those assigned to aspirin (3.6% per year; p = 0.02; 95% confidence interval, 9-63%).

In the subgroup of warfarin-eligible patients (most less than 76 years old), warfarin dose-adjusted to prolong prothrombin time to 1.3-fold to 1.8-fold that of control reduced the risk of primary events by 67% (warfarin vs. placebo, 2.3% vs. 7.4% per year; p = 0.01; 95% confidence interval, 27-85%).

Primary events or death were reduced 58% (p = 0.01) by warfarin and 32% (p = 0.02) by aspirin.

The risk of significant bleeding was 1.5%, 1.4%, and 1.6% per year in patients assigned to warfarin, aspirin, and placebo, respectively.


Because of the weight of evidence that both aspirin and warfarin were superior to placebo, patients in the group eligible to receive warfarin were not assigned to placebo after the first 1.13 years of follow-up.

Aspirin and warfarin are both effective in reducing ischemic stroke and systemic embolism in patients with atrial fibrillation. Because warfarin-eligible patients composed a subset of all aspirin-eligible patients, the magnitude of reduction in events by warfarin vs. aspirin cannot be compared. Too few events occurred in warfarin-eligible patients to directly assess the relative benefit of aspirin compared with warfarin, and the trial is continuing to address this issue. Patients with nonrheumatic atrial fibrillation who can safely take either aspirin or warfarin should receive prophylactic antithrombotic therapy to reduce the risk of stroke.


1. N Engl J Med 1990;322:863-868. Preliminary results
2. Circulation 1991;84:527-539. Final results

Clinical Topics: Anticoagulation Management, Valvular Heart Disease

Keywords: Stroke, Follow-Up Studies, Platelet Aggregation Inhibitors, Warfarin, Fibrinolytic Agents, Electrocardiography, International Normalized Ratio, Prothrombin Time, Mitral Valve Stenosis, Embolism, Confidence Intervals, Hemorrhage

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