Prevention of Recurrent Venous Thromboembolism N Engl J Med Apr ;348(15) : PREVENT (Warfarin) Trial

www. Clinical trial results.org Warfarin (target INR, ) (n = 255) Warfarin (target INR, ) (n = 255) Placebo (n = 253) Placebo (n = 253) Endpoints (mean follow-up 2.1 years):  Primary – 1) recurrent venous thromboembolism and 2) composite of recurrent venous thromboembolism, major hemorrhage, or death Endpoints (mean follow-up 2.1 years):  Primary – 1) recurrent venous thromboembolism and 2) composite of recurrent venous thromboembolism, major hemorrhage, or death PREVENT Trial N Engl J Med Apr ;348(15) : Open-label therapy for 28 days  To determine if warfarin dose could be titrated to an INR of 1.5 to 2.0 without exceeding 10 mg per day  To see if patients could maintain a compliance of 85% Open-label therapy for 28 days  To determine if warfarin dose could be titrated to an INR of 1.5 to 2.0 without exceeding 10 mg per day  To see if patients could maintain a compliance of 85% 508 patients with documented idiopathic venous thromboembolism, >3 uninterrupted months of oral anticoagulation therapy with full-dose warfarin  Age >30 years 508 patients with documented idiopathic venous thromboembolism, >3 uninterrupted months of oral anticoagulation therapy with full-dose warfarin  Age >30 years

www. Clinical trial results.org PREVENT Trial: Composite Endpoint Placebo N Engl J Med Apr ;348(15) : * Composite of recurrent thromboembolism, major bleed and death Composite Endpoint* HR = 0.52, p=0.01 Trial discontinued early by the DSMB, due to a large, significant benefit with low- intensity warfarin therapy and the absence of any substantial evidence of any significant untoward side effects Warfarin

www. Clinical trial results.org PREVENT Trial N Engl J Med Apr ;348(15) : Warfarin Placebo Recurrent Venous Thromboembolism HR = 0.36, p<0.001 Warfarin Placebo All-Cause Mortality HR = 0.50, p=0.26

www. Clinical trial results.org PREVENT: Conclusions Among patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for six months, treatment with low-intensity warfarin (target INR, ) was associated with a reduction in recurrent venous thromboembolism and in the composite of recurrent venous thromboembolism, major hemorrhage, or death during follow-up No significant excess major bleeding occurred in the warfarin arm First randomized trial to examine the use of low-intensity warfarin therapy, rather than full-dose therapy in this population Among patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for six months, treatment with low-intensity warfarin (target INR, ) was associated with a reduction in recurrent venous thromboembolism and in the composite of recurrent venous thromboembolism, major hemorrhage, or death during follow-up No significant excess major bleeding occurred in the warfarin arm First randomized trial to examine the use of low-intensity warfarin therapy, rather than full-dose therapy in this population