Patients with atrial fibrillation who took warfarin in dosages to maintain an international normalised ratio (INR) in the recommended range had fewer ischaemic strokes, less severe strokes, and were less likely to die than patients who took lower doses of warfarin or who took aspirin or no treatment, reports a large study in the New England Journal of Medicine ( 2003; 349: 1019-26).
Atrial fibrillation can lead to the formation of clots that travel to the brain. It causes 80 000 strokes in the United States each year.
The study involved 13 559 patients with non-valvular atrial fibrillation who were members of Kaiser Permanente, a US healthcare organisation. In the 18 months of the study (July 1996 to December 1997) there were 596 ischaemic strokes, almost all of which were confirmed by cranial computed tomography or magnetic resonance imaging. Of the strokes 32% occurred in patients taking warfarin, 27% in patients taking aspirin, and 42% in patients who were not taking an anticoagulant.
Use of aspirin and warfarin was noted in admission charts, and anticoagulation levels after warfarin treatment were measured on patients' admission to hospital. However, there is no clinically useful way to measure the anticoagulation effect of aspirin or whether the patient has been taking aspirin as recommended.
Only 5% of the patients who were taking warfarin and whose INR was in the recommended range of 2.0 to 3.0 died or were discharged with disability resulting from a severe stroke, said the lead author, Dr Elaine Hylek, assistant professor of medicine at Harvard Medical School and Massachusetts General Hospital. This compared with 15% of patients whose INR was less than 2.0 and 13% of patients taking aspirin. The corresponding figure for patients receiving no anticoagulant was 22%.
The study used the Rankin scale to measure functional deficits of daily living. This scale rates patients according to whether they need 24 hour care, whether they have muscular weakness or partial paralysis on one side of the body, or whether they just have a clumsy left hand.
Dr Hylek said that although it was known that warfarin reduces the risk of stroke, this study showed that it was important that the INR remained in the recommended range of 2.0 to 3.0 in order to reduce the risk of stroke, the severity of stroke, and mortality.
She said that doctors sometimes reduce the dosage of warfarin for patients aged over 75, but the study showed that an INR below 2.0 increased the likelihood that a stroke would be fatal or cause serious disability.
“What the study contributes is confidence in target levels of 2.0 to 3.0,” she said.