Efficacy of dabigatran versus warfarin in patients with acute venous thromboembolism in the presence of thrombophilia: Findings from RE-COVER^®, RE-COVER™ II, and RE-MEDY™

Abstract

It is unclear whether thrombophilia causes resistance to anticoagulant therapy. Post hoc analyses of data from RE-COVER, RE-COVER II, and RE-MEDY were performed to compare dabigatran etexilate with warfarin for the treatment and prevention of venous thromboembolism (VTE) in patients with thrombophilia or antiphospholipid antibody syndrome (APS). There were no significant differences in symptomatic VTE/VTE-related deaths between dabigatran etexilate and warfarin in patients with or without thrombophilia. All bleeding event categories were less frequent with dabigatran etexilate than with warfarin, regardless of whether patients had thrombophilia, no thrombophilia, or were not tested. However, these differences did not reach significance in every group. In patients with APS, there was no significant difference in VTE/VTE-related deaths between the two treatment arms. Rates of bleeding events tended to be lower with dabigatran etexilate than with warfarin, reaching statistical significance for any bleeding event. In conclusion, the efficacy and safety of dabigatran etexilate were not significantly affected by the presence of thrombophilia or APS. ClinicalTrials.gov RECOVER IDENTIFIER NCT00291330; RECOVER II IDENTIFIER NCT00680186; RE-MEDY IDENTIFIER NCT00329238.

Seronegative antiphospholipid syndrome: refining the value of “non-criteria” antibodies for diagnosis and clinical management

“…72 An analysis from the RE-COVER/RE-COVER II and RE-MEDY trials showed similar safety and efficacy of dabigatran in patients with thrombophilia and previous venous thromboembolic events, in whom APS represented the second most common inherited disorders, accounting for 20% of all patients. 79 These results need to be confirmed in realworld studies. A randomized trial investigating the efficacy and safety of apixaban in APS patients is currently ongoing; 80 this study will include patients with both venous and arterial thrombosis.…”

Clinical use and laboratory testing of oral anticoagulation therapy: experience from Finland

“…Currently for patients with hereditary thrombophilia, DOACs are not usually the primary anticoagulant recommended under these conditions (9)(10)(11)59). In the RE-MEDY trial, small subgroup analysis, dabigatran seemed noninferior to warfarin in thrombophilia patients (protein C or S deficiency, antithrombin deficiency, antiphospholipid antibodies, FV Leiden or prothrombin variant heterozygous mutation) (62). Rivaroxaban was assessed as noninferior to warfarin in phospholipid antibody syndrome (APS) in a phase III trial (63); however, the most severe APS patients did not benefit from rivaroxaban in comparison with warfarin (64).…”

How I treat recurrent venous thromboembolism in patients receiving anticoagulant therapy

“…One of the NOACs could be a more convenient alternative for this patient once she stops breastfeeding, and there are emerging data from case series 54 and subgroup analyses from larger trials 22 that NOACs are similarly effective in patients with antiphospholipid syndrome. However, until a current randomized trial has demonstrated efficacy results, 55 NOACs should not be the first line of treatment because failures have been reported.…”

“…22 It has been speculated that deficiency of antithrombin may be associated with heparin resistance. In a retrospective review of 70 patients with congenital antithrombin deficiency, we found 8 patients in whom there was some clinical deterioration on treatment with unfractionated heparin.…”