Warfarin is recommended by the American College of Chest Physicians (ACCP) as a treatment option for the management of patients with venous thromboembolism (DVT or PE). The ACCP recommends treatment for at least 3 months after a VTE with consideration of long-term treatment in patients at high-risk of recurrence.1 While warfarin is inexpensive and has extensive evidence supporting its effectiveness, it is associated with a risk of major/minor bleeding and requires frequent monitoring and dose adjustments which makes it more challenging to use for long-term treatment. Dabigatran (Pradaxa®), an oral direct thrombin inhibitor, was found to be non-inferior to warfarin in the initial 6-months trial for treatment of venous thromboembolism (RE-COVER and RE-COVER II).2 Dabigatran was associated with less major bleeding episodes and showed potential to be a long-term therapy option after initial therapy for VTE.
Schulman and colleagues reported the results of two recent clinical trials comparing dabigatran to warfarin (RE-MEDY) and dabigatran to placebo (RE-SONATE) in evaluating the efficacy and safety of dabigatran for long-term secondary prophylaxis after treatment for VTE. The active-control study (dabigatran vs. warfarin) enrolled 2,866 patients and the placebo-control (dabigatran vs. placebo) enrolled 1,323 patients who completed at least 3 months of treatment for a proximal DVT or PE in these double-blinded, multicentered, international, randomized studies. The primary end point for both studies was recurrent or fatal VTE and the secondary end points were non-fatal pulmonary embolism or DVT. The safety outcome was having a major bleeding event.3
The mean age was 54-56 years, about 90% of participants were white and almost two-thirds of patients had a DVT as the index event. The warfarin group in the active-control study was found to have an INR in range 65.3% of the time. The results showed dabigatran to be non-inferior to warfarin for prevention of recurrent VTE (HR 1.44, 95% CI, 0.78 to 2.64), with fewer incidences of major bleeding or clinically relevant non-major bleeding events (HR 0.54, 95% CI, 0.41 to 0.71) with extending therapy. The margin set for the non-inferiority HR comparing dabigatran to warfarin was large (2.85), and warfarin still showed less incidence of the recurrent or fatal DVT or PE (26 events with dabigatran to 18 with warfarin). Similar to the findings in the RE-LY study, warfarin was associated with less acute coronary syndromes compared to dabigatran. In comparing dabigatran to placebo, dabigatran decreased recurrent or fatal VTE (HR 0.08, 95% CI, 0.02 to 0.25) with a higher rate of major bleeding or other bleeding events (HR 2.92, 95% CI, 1.52 to 5.60) with long-term therapy.3
In conclusion, these studies showed that dabigatran could be considered as an option for prevention of VTE after initial treatment and carries less risk of bleeding than warfarin. However, dabigatran’s efficacy may be questionable compared to warfarin and further studies are needed. In weighing the benefit vs. the risk, treatment of 200 individuals with warfarin therapy over dabigatran would prevent ...