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Title: Patients with nonvalvular atrial fibrillation at low risk of stroke during treatment with aspiring: Stroke prevention in atrial fibrillation III study

Authors:  The SPAF III writing committee for the Stroke Prevention in Atrial Fibrillation investigators.

Reference:  JAMA. 279:1273-7. April 22/29, 1998.

Reference: Michael Jacobson

Problem addressed: Atrial fibrillation is a common condition, which carries with it a significant risk for stroke. Treatment with adjusted-dose warfarin significantly reduces this risk, but at the price of an increased risk for hemorrhage.  Treatment with aspirin also reduces the risk for stroke, less effectively than warfarin, but could be an attractive modality for those at low risk for stroke.    

Purpose of study: To evaluate the stroke risk in a group of patients at low risk for thromboembolism, who were treated with aspirin only. 

Methods: Approximately 900 patients with atrial fibrillation and low risk for thromboembolism (not lone fibrillators) were followed for a mean of 2 years.  All patients who were eligible and participated in the study received enteric-coated aspirin, 325 mg daily. 

Results:  Patients had a mean age of 67 years, were 78% male, had mean blood pressure of 130/70, 46% had a history of hypertension.

The primary event rate (ischemic stroke and systemic emboli) was 2.2% per year (95% CI 1.6-3.0%).  The rate of ischemic stroke was 2.0%, disabling stroke 0.8% and TIA (not a primary event) 1.3%.

Discussion: In this group, the stroke rate is around 1% per year if the patients are treated with aspirin alone, which is similar to the stroke rate in the general age-matched population. Treatment with warfarin may not add any significant benefit. 

In patients with any of the four risk factors (impaired LV function; active hypertension, prior stroke, transient ischemic attack or arterial embolism; female aged more than 75 years) the event rate is much higher: around 8% per year even when treated with aspirin and low-dose warfarin.

The authors note that this trial did not directly compare aspirin with either placebo or warfarin. Thus, the degree of benefit conferred by aspirin treatment cannot be inferred from the data presented here. The added protection that might be gained by using warfarin in these patients can also not be directly deduced, although the authors use comparisons to other studies to suggest that it would be relatively low, and at a price of an increased risk of hemorrhage.

Comments: Patients with "lone atrial fibrillation" who are under 60 years of age, not hypertensive, without evidence of cardiovascular disease and who have normal echocardiograms, are at sufficiently low risk for stroke that warfarin therapy is unlikely to be of significant benefit. Patients who do not fall into this category (the vast majority) have been shown to benefit from anticoagulation.

This study should not be interpreted as showing that warfarin therapy in atrial fibrillation isn't as important as it would seem to be. The recent trend in therapy for atrial fibrillation has been to be much more liberal with anticoagulation, and the current study does not invalidate this trend. What it does do, however, is define a very specific subgroup of patients who can probably be managed with aspirin alone. This subgroup represents a minority of patients, but a significant one.  Since this trial did not compare aspirin therapy to warfarin, it is very possible that warfarin therapy would reduce the stroke rate in this population even further. Given the low incidence of stroke on aspirin however, and the not insignificant risk of hemorrhage with warfarin, the overall benefit is not likely to be large. 

To be eligible for this strategy, patients must not have mitral stenosis, any history of hypertension, congestive heart failure (clinically or by echocardiography), any history of CVA, TIA or embolism and they should not be women over 75 years of age.