"Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism". The New England Journal of Medicine. 2009. 361(24):2342-2352. PubMed•Full text•PDF
Clinical Question
In patients with acute venous thromboembolism, is dabigatran an effective alternative to warfarin for anticoagulation?
Bottom Line
In patients with acute venous thromboembolism, dabigatran was found to be noninferior to warfarin in terms of preventing recurrent events, had a similar safety profile, and did not require laboratory monitoring.
Major Points
Warfarin has been the mainstay therapy for venous thromboembolism but requires frequent INR monitoring and dietary restrictions. Dabigatran, a direct thrombin inhibitor, may offer an easier-to-use alternative without needing routine blood coagulation testing.
Guidelines
No guidelines were provided within this article.
Design
Randomized, double-blind, double-dummy, noninferiority trial comparing dabigatran with warfarin following initial parenteral anticoagulation therapy. Each patient received 6 months of treatment.
Population
A total of 2,564 patients with acute venous thromboembolism:
- Inclusion criteria: Adults ≥18 years with acute proximal deep-vein thrombosis of the legs or pulmonary embolism requiring 6 months of anticoagulation
- Exclusion criteria: Prolonged (>14 days) symptoms, hemodynamically unstable pulmonary embolism requiring thrombolysis, other indications for warfarin, recent unstable cardiovascular disease, high risk of bleeding, severe liver disease, creatinine clearance <30 ml/min, pregnancy or risk of pregnancy, and long-term antiplatelet therapy
Interventions
- Dabigatran (150 mg twice daily) after initial parenteral anticoagulation
- Warfarin (dose-adjusted to achieve INR 2.0-3.0) after initial parenteral anticoagulation
Outcomes
- Primary outcome: Frequency of recurrent symptomatic, objectively confirmed venous thromboembolism and related deaths over 6 months
- Safety end points: Bleeding episodes, acute coronary syndromes, other adverse events, liver function tests
- Dabigatran group had 30 events (2.4%) vs. 27 events (2.1%) in the warfarin group
- Hazard ratio for dabigatran was 1.10 (95% CI, 0.65 to 1.84), meeting criteria for noninferiority (P<0.001)
- Major bleeding: 20 cases (1.6%) in dabigatran group vs. 24 cases (1.9%) in warfarin group (hazard ratio 0.82; 95% CI, 0.45 to 1.48)
Criticisms
- First dose of dabigatran was only given after initial parenteral anticoagulation therapy for a median of 9 days; no evidence for monotherapy use at the acute phase
- The study's population was predominantly white and had good renal function, limiting generalizability
Funding
Boehringer Ingelheim (manufacturer of dabigatran).
Further Reading
ClinicalTrials.gov number, NCT00291330.