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The US Food and Drug Administration (FDA) has approved the direct thrombin inhibitor dabigatran etexilate mesylate (Pradaxa) for the prophylaxis of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients who have undergone hip replacement surgery.
Dabigatran was initially approved by the FDA in 2010 to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation.
In 2014, dabigatran was approved to treat DVT and PE in patients who have been treated with a parenteral anticoagulant for 5 to 10 days and to reduce the risk of recurrent DVT and PE in patients who have been previously treated.
A reversal agent for dabigatran, known as idarucizumab (Praxbind), was approved by the FDA last month.
Trial data
The latest approval of dabigatran is based on results of 2 randomized, double-blind, phase 3 trials in patients undergoing total hip replacement, RE-NOVATE™ and RE-NOVATE II™.
In the RE-NOVATE trial, 3494 patients were randomized to 3 groups receiving prophylactic treatment with 1 of 2 doses of dabigatran (220 mg or 150 mg) once daily or enoxaparin at 40 mg once daily for 28 to 35 days.
The first dabigatran group was given a dose of 110 mg on the day of surgery and 220 mg daily thereafter. The second dabigatran group received a dose of 75 mg on the day of surgery and 150 mg daily thereafter.
Patients taking dabigatran at 220 mg had a lower composite total of venous thromboembolism (VTE) and all-cause death (6.0%) than patients on enoxaparin (6.7%). However, the rate of major bleeding was higher with dabigatran at 220 mg (2.0%) than with enoxaparin (1.6%).
In the RE-NOVATE II trial, 2055 patients were randomized to prophylactic treatment for 28 to 35 days with dabigatran at 220 mg once daily or enoxaparin at 40 mg once daily. Patients receiving dabigatran were treated with a dose of 110 mg on the day of surgery and 220 mg daily thereafter.
The composite total of VTE and all-cause death occurred in 7.7% of patients in the dabigatran group and 8.8% of patients in the enoxaparin group. Again, the rate of major bleeding was higher with dabigatran at 220 mg (1.4%) than with enoxaparin (0.9%).
In both studies, the rate of major gastrointestinal bleeds in patients receiving dabigatran and enoxaparin was the same (0.1%). The rate of any gastrointestinal bleeds was 1.4% for dabigatran and 0.9% for enoxaparin.
The most common adverse events in both studies were gastrointestinal disorders. The incidence was the same across the dabigatran and enoxaparin treatment groups (39.5%).
Dyspepsia (including abdominal pain upper, abdominal pain, abdominal discomfort, and epigastric discomfort) occurred more frequently in patients receiving dabigatran (4.1%) than enoxaparin (3.8%).
Gastritis-like symptoms (including gastritis, GERD, esophagitis, erosive gastritis, and gastric hemorrhage) were less common in patients receiving dabigatran (0.6%) than enoxaparin (1.0%). Clinical myocardial infarction was reported in 2 (0.1%) dabigatran patients and 6 (0.3%) enoxaparin patients.
Dabigatran is marketed as Pradaxa by Boehringer Ingelheim. For more details on the drug, see the prescribing information.
