Influence of Thrombophilia on the Efficacy of Dabigatran Versus Warfarin for the Extended Treatment of Acute Venous Thromboembolism in RE-MEDY™

Abstract

▪Background: Dabigatran etexilate (DE) was noninferior to warfarin for the prevention of recurrent venous thromboembolism (VTE), with a lower risk of bleeding, when administered as extended treatment for VTE in the RE-MEDY™ study (in which we evaluated long-term extension of treatment with dabigatran compared with warfarin).Objectives: Thrombophilia is a major risk factor for VTE recurrence. Therefore, we performed a post-hocsubgroup analysis on data from RE-MEDY™ to investigate the efficacy of DE versus warfarin in patients with and without thrombophilia (congenital or acquired) at baseline.Methods: Patients were aged ≥ 18 years and had objectively-confirmed, symptomatic, proximal deep vein thrombosis or pulmonary embolism (PE) that had been treated with an approved anticoagulant for 3–12 months, or with DE in one of two clinical trials of treatment for acute VTE (RE-COVER™ or RE-COVER™ II). Eligible patients were those at increased risk for recurrent VTE. Patients were randomly allocated to receive DE 150 mg twice daily or warfarin (international normalized ratio range 2.0–3.0) for 6–36 months. The primary efficacy outcome was recurrent, symptomatic, objectively-confirmed VTE or VTE-related death from randomization up to the end of the planned treatment period (6–36 months). No thrombophilia workup was required for enrollment in the trial.Results: Overall, 262/1430 (18.3%) patients randomized to DE and 263/1426 (18.4%) randomized to warfarin had thrombophilia identified at baseline. Factor V Leiden thrombophilia was the most common type (Table). The frequencies of VTE/VTE-related deaths, and of PE, in patients with and without thrombophilia are shown in the Table. Treatment efficacy (DE versus warfarin) was not significantly affected by the presence of thrombophilia.TableDE (n = 1430)Warfarin (n = 1426)Thrombophilia, n (%)No433 (30.3)407 (28.5)Yes262 (18.3)263 (18.4)Factor V Leiden131 (9.2)137 (9.6)Prothrombin mutation35 (2.4)28 (2.0)Antithrombin deficiency11 (0.8)11 (0.8)Protein C/S deficiencies25 (1.7)29 (2.0)Antiphospholipid antibodies and/or lupus anticoagulants38 (2.7)54 (3.8)Not tested735 (51.4)756 (53.0)VTE/VTE-related deaths, n/N (%)Pulmonary embolism,n/N (%)DEWarfarinDEWarfarinThrombophiliaNo10/433 (2.3)3/407 (0.7)3/433 (0.7)1/407 (0.2)Yes4/262 (1.5)6/263 (2.3)3/262 (1.1)2/263 (0.8)Not tested12/735 (1.6)9/756 (1.2)4/735 (0.5)2/756 (0.3)Total study population: Hazard ratio (DE vs warfarin) (95% confidence interval)1.43 (0.78, 2.61) 1.97 (0.67, 5.76)Treatment (DE vs warfarin) by thrombophilia interactionp = 0.2277p = 0.9003p-value from Chi-square test for overall factor effect. Full analysis set.Conclusions: The frequencies of VTE/VTE-related death, and of PE, were similar for DE and warfarin in patients with thrombophilia who were receiving extended treatment for VTE. Treatment efficacy was not affected by the presence of thrombophilia. DisclosuresSchulman:Boehringer Ingelheim: Consultancy, Honoraria, Research Funding; Bayer HealthCare: Consultancy, Honoraria, Research Funding. Eriksson:Boehringer Ingelheim: Consultancy; BMS: Consultancy; Pfizer: Consultancy. Goldhaber:Boehringer Ingelheim: Consultancy; Daiichi: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Janssen: Consultancy; Merck: Consultancy; Pfizer: Consultancy; Portola: Consultancy; Sanofi-Aventis: Consultancy. Kakkar:Boehringer Ingelheim: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Daiichi: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Eisai: Consultancy, Honoraria, Research Funding. Kearon:Bayer Healthcare: Consultancy; Boehringer Ingelheim (Canada): Consultancy. Schellong:Boehringer Ingelheim: advisory boards Other, Consultancy, Honoraria; Bayer Healthcare: advisory boards, advisory boards Other, Consultancy, Honoraria; Daiichi Sankyo: advisory boards, advisory boards Other, Honoraria; BMS/Pfizer: Honoraria. Feuring:Boehringer Ingelheim: Employment. Friedman:Boehringer Ingelheim: Consultancy. Kreuzer:Boehringer Ingelheim: Employment.