Comparison of Low-Intensity Warfarin Therapy With Conventional-Intensity Warfarin Therapy for Long-Term Prevention of Recurrent Venous Thromboembolism

Observations suggest that traditional anticoagulant therapy, maintaining an international normalized ratio (INR) of approximately 2.0 to 3.0, could be more intensive than is necessary for the long-term prevention of recurrent venous thromboembolism. The value of less-intensive warfarin anticoagulation, with a target INR of 1.5 to 1.9, was therefore examined in a randomized, double-blind study enrolling 738 consecutive patients having one or more episodes of venous thromboembolism. All had completed at least 3 months of conventional oral anticoagulant therapy. Participants were assigned to continue on warfarin with a target INR of either 2.0-3.0 or 1.5-1.9 and were followed up for 2.4 years on average. To be eligible, patients must have had confirmed, symptomatic, proximal deep venous thrombosis or pulmonary embolism with no apparent major risk factor. The mean INR was 1.8 for patients assigned to low-intensity treatment and 2.4 in the usual-intensity group. Nine major bleeding episodes occurred in patients on low-intensity treatment, for a rate of 1.1 per 100 person-years. The 8 such episodes in the traditional treatment group represented a rate of 0.9 per 100 person-years. Including minor bleeding episodes, rates were 4.9 and 3.7 per 100 person-years, respectively. There were no fatal or intracranial bleeds in either treatment group. Older patients were more likely to have major bleeding. Venous thromboembolism recurred at rates of 1.9 events per 100 person-years in the low-intensity group and 0.7 per 100 person-years with traditional treatment, a statistically significant difference. Five episodes in the low-intensity group and 3 in the usual-intensity group occurred after warfarin was discontinued. There was 1 death in the low-intensity group caused by pulmonary embolism and 2 such deaths in the conventional treatment group. These findings show that conventional warfarin anticoagulation is more effective than a low-intensity regimen for preventing recurrent venous thromboembolism; the risk is lowered by approximately two thirds. At the same time, low-intensity treatment does not appear to make bleeding less likely.