1. PREVENT (Warfarin) Trial Prevention of Recurrent Venous Thromboembolism N Engl J Med Apr 10 2003;348(15) :1425-1434

2. PREVENT Trial • 508 patients with documented idiopathic venous thromboembolism, >3 uninterrupted months of oral anticoagulation therapy with full-dose warfarin • Age >30 years • 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% Warfarin (target INR, 1.5-2.0) (n = 255) 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 N Engl J Med Apr 10 2003;348(15) :1425-1434

3. PREVENT Trial: Composite Endpoint 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 * Composite of recurrent thromboembolism, major bleed and death Placebo Warfarin N Engl J Med Apr 10 2003;348(15) :1425-1434

4. PREVENT Trial All-Cause Mortality HR = 0.50, p=0.26 Recurrent Venous Thromboembolism HR = 0.36, p<0.001 Placebo Warfarin Warfarin Placebo N Engl J Med Apr 10 2003;348(15) :1425-1434

5. 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, 1.5-2.0) 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