Efficacy of delayed thromboprophylaxis with dabigatran: pooled analysis

Abstract

Introduction: Oral thromboprophylaxis with dabigatran etexilate should be initiated as a half dose 1 to 4h after major orthopaedic surgery. However, a delay in dosing could occur for clinical or logistical reasons. A post hoc analysis was carried out to determine if patients with delayed dosing received adequate anticoagulation.

Patients and methods: The RE-MODEL™ and RE-NOVATE® trials compared 220 mg and 150 mg dabigatran etexilate with 40 mg enoxaparin. Pooled data for major venous thromboembolism (VTE) and VTE-related mortality (efficacy outcome) and major bleeding events (MBE), MBE/clinically relevant bleeding events, and all bleeding events (safety outcomes) were analysed. Results in patients with dosing delayed more than 4h postsurgery were compared with those of patients without a delay.

Results: Onset of treatment was delayed in 724 (13.3%) of 5425 patients. Efficacy of 220 mg dabigatran etexilate was similar in patients without delayed dosing, patients with a delay and patients with a delay until the day after surgery. Rates of efficacy outcome were higher in patients on 150 mg dabigatran etexilate, but more than 80% of these patients were undertreated based on age or renal clearance status. Some differences in bleeding events were seen among patient groups by treatment arm.

Conclusion: Dabigatran etexilate thromboprophylaxis should be initiated 1 to 4h postsurgery. Results from our post-hoc analysis indicate that no loss of efficacy appears to occur if initiation of dabigatran etexilate 220 mg needs to be delayed.

Trial registration: ClinicalTrials.gov NCT00168805 NCT00168818.