Aspirin for Atrial Fibrillation Stroke Prevention
ABSTRACT & COMMENTARY
Synopsis: The authors conclude that AF patients at low risk for stroke on aspirin can only be reliably identified by clinical criteria.
Source: SPAF Investigators. JAMA 1998;279:1273-1277.
Although adjusted-dose warfarin is the standard for stroke prevention in patients with non-valvular atrial fibrillation (AF), such patients are a heterogeneous group with widely variable stroke rates within subgroups. Thus, a reliable method for identifying low-risk AF patients who could be treated with aspirin alone, would be valuable. The Stroke Prevention in AF (SPAF) III study prospectively identified patients with non-valvular AF who lacked previously determined thromboembolic risk factors, put them on aspirin alone and assessed their thromboembolic event rate over two years. Low-risk outpatients were defined based on the absence of four factors: recent heart failure or reduced left ventricular function; systolic blood pressure lower than 160 mmHg; previous thromboembolism; or females older than 75 years. Patients with intermittent AF were included, but lone AF patients younger than 60 years old were not. The hypothesis being tested was that the study patients would have an embolic event rate of less than 3% per year on 325 mg aspirin/d. Twenty centers in North America enrolled 892 patients with a mean age of 67 ± 10 years; 78% were men, 46% had hypertension, 13% had diabetes, and 16% had ischemic heart disease. Despite the fact that patients developed risk factors for thromboembolism at a rate of 6% per year, the primary event rate was 2% per year, without appreciable change over three years. Also, disabling strokes occurred less than 1% per year, and only half the strokes were clearly cardioembolic in origin. A history of hypertension increased the observed stroke rate to 4% per year. The only other statistically significant predictor of stroke was age, with a relative risk increase of 1.7 per 10 years. The major bleeding rate was 0.5% per year, and almost all were gastrointestinal bleeds. The authors conclude that AF patients at low risk for stroke on aspirin can only be reliably identified by clinical criteria.
Table
Risk factors for an embolic event in non-valvular AF patients
| Negligible risk | Lone AF, age younger than 60 years
|
| Low risk | Absence of:
Hypertension
Prior stroke CHF or LV dysfunction Women older than 75 years |
| Intermediate risk | Hypertension |
| High risk | Two or more of the factors above |
COMMENT BY MICHAEL H. CRAWFORD, MD
This SPAF study provides confirmation that there are low-risk non-valvular AF groups that do not need warfarin therapy. Analysis of the entire SPAF database suggests that this group may represent 50% of AF patients. This study suggests that patients can be divided into three risk groups: a low-risk group (embolic event rate, 1% per year) with no hypertension, no left ventricular dysfunction, no prior embolic events, and no women older than 75 years; an intermediate-risk group (stroke rate, 3-4% per year) with hypertension; and a high-risk group (embolic rate, 8% per year) with two or more of the four risks listed above. The high-risk group clearly benefits from adjusted-dose warfarin, as do patients with valvular disease and other indications for warfarin. The real issue is the treatment of the rest of the AF patients.
This study suggests that the low-risk group should get aspirin, but there is no control group, so we do not know if aspirin contributed to the low risk in this group. In fact, previous data suggest that lone AF patients younger than 60 years of age do not require any therapy. Perhaps these older low-risk patients are similar. On the other hand, the authors point out that high-risk factors develop at a rate of 6% per year in the low-risk group, which suggests that either frequent surveillance, prophylactic therapy with aspirin, or both would be prudent. In fact, the risk of aspirin therapy was low in this group. Whether aspirin would be sufficient in the intermediate risk group with hypertension, or whether warfarin is required is not known. Alternatively, perhaps tight control of the blood pressure plus aspirin would be adequate.
This study and others reported in this issue shed more light on this vexing but growing problem of the management of AF patients. The good news is that the group who do not need warfarin seems to be getting larger as more data are accumulating. (Dr. Crawford is Robert S. Flinn Professor, Chief of Cardiology, University of New Mexico, Albuquerque.)
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