Low-Intensity Warfarin for Long-Term Prevention of Venous Thromboembolism

In a study on the effectiveness of low-intensity warfarin in preventing recurrent venous thromboembolism 1, 508 subjects were randomized to either placebo or low-intensity warfarin. The patients with idiopathic venous thromboembolism had received full-dose anticoagulation therapy for a median of 6.5 months before randomization (target INR, 1.5 to 2.0). The trial was terminated early when the 508 patients had been followed for up to 4.3 years. The incidence of recurrent venous thromboembolism was 7.2 per 100 person-years in the placebo group as compared with 2.6 per 100 person-years in the group on low-intensity warfarin, a risk reduction of 64 percent (hazard ratio 0.36; 95% CI 0.19 to 0.67; p<0.001). Risk reductions were similar for all subgroups. Low-intensity warfarin was associated with a 48 percent reduction in the composite end point of recurrent venous thromboembolism, major hemorrhage, or death. According to per-protocol and as-treated analyses, the reduction in the risk of recurrent venous thromboembolism was between 76 and 81 percent.

In another randomized, double-blind study 2 738 patients who had completed at least three months of warfarin therapy for unprovoked venous thromboembolism were randomly assigned to continue warfarin therapy with a target INR of 2.0 to 3.0 (conventional intensity) or a target INR of 1.5 to 1.9 (low intensity). Patients were followed for an average of 2.4 years. The incidence of recurrent venous thromboembolism was 1.9 per 100 person-years in the low-intensity therapy group as compared with 0.7 per 100 person-years in the conventional-intensity therapy group (hazard ratio 2.8; 95% CI 1.1 to 7.0). The incidence of major bleeding episodes was 1.1 events per 100 person-years and 0.9 event per 100 person-years, respectively (hazard ratio 1.2; 95% CI 0.4 to 3.0). There was no significant difference in the frequency of overall bleeding between the two groups (hazard ratio 1.3; 95% CI 0.8 to 2.1).

Comment: The quality of evidence is downgraded by imprecise results (limited study size for each comparison).

References

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