Canadian Atrial Fibrillation Anticoagulation Study - CAFA


The Canadian Atrial Fibrillation Anticoagulation Study (CAFA) was a randomized trial of warfarin versus placebo for the primary prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF). The trial had planned enrollment of 630 subjects with average follow-up of 2.5 years, but was terminated early after randomizing 383 subjects, due to the interim publication of two major studies supporting the safety and efficacy of warfarin for this indication.


Systemic anticoagulation with warfarin will prevent thromboembolic events, including stroke, in patients with AF.

Study Design

Study Design:

Patients Enrolled: 383
Mean Follow Up: Mean 15.2 months
Mean Patient Age: 68 ± 9 years
Female: 25

Patient Populations:

Adults with at least three episodes of paroxysmal AF in the prior three months, or persistent AF for ≥1 month, in the absence of mitral stenosis or prosthetic heart valve


1) Unrelated requirement for anticoagulation or antiplatelet therapy.
2) Contraindication to anticoagulation.
3) Stroke or transient ischemic attack within one year.
4) Hyperthyroidism.
5) Uncontrolled hypertension.
6) Myocardial infarction within one month.

Primary Endpoints:

Any one of the following: ischemic stroke (nonlacunar), systemic embolism, intracranial hemorrhage, or fatal bleeding event

Secondary Endpoints:

1) Transient ischemic attack.
2) Lacunar stroke.
3) Major noncerebral bleeding event (bleed requiring transfusion, ≥20 g/l fall in hemoglobin, or in anatomically sensitive location, e.g., retina).
4) Minor bleeding.
5) Death.

Drug/Procedures Used:

Warfarin, dose-adjusted to maintain an international normalized ratio (INR) of 2-3, or matching placebo

Concomitant Medications:

Patients with a requirement for antiplatelet drug therapy were excluded; those enrolled were advised not to take aspirin or nonsteroidal anti-inflammatory drugs during the trial.

Principal Findings:

For warfarin-treated patients, INRs were in the therapeutic range 44% of the time; below 39%, and above 17%. By intention-to-treat analysis, the primary endpoint was reached in 8/187 (4.3%) of warfarin patients versus 11/191 (5.8%) of placebo patients (p=NS), a relative risk reduction (RRR) of 26%.

In on-treatment analysis, stroke or systemic embolism occurred in 2.7% of warfarin patients versus 5.8% of placebo patients, a RRR of 55% (p=0.07). The rate of on-treatment fatal or major hemorrhage was 2.5% per year in the warfarin group versus 0.5% per year in the placebo group (p=NS).

The authors concluded that their results were consistent with those of the SPAF and AFASAK studies, further supporting the use of warfarin for this indication.


Among patients with nonrheumatic AF, warfarin was associated with a nonsignificant reduction in the risk of stroke and systemic embolism compared with placebo, with a slight increase in the risk of serious hemorrhage. Limited conclusions can be drawn from the present study since enrollment was noncompleted (~60%), given the positive findings observed in two other large randomized trials of warfarin therapy.


Connolly SJ, Laupacis A, Gent M, Roberts RS, Cairns JA, Joyner C. Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. J Am Coll Cardiol 1991;18:349-55.

Clinical Topics: Anticoagulation Management, Prevention, Valvular Heart Disease

Keywords: Risk, Stroke, Warfarin, Mitral Valve Stenosis, Intention to Treat Analysis, Canada, Embolism, Heart Valves, Hemorrhage, Primary Prevention

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