Safety and efficacy of direct oral anticoagulants compared to warfarin for extended treatment of venous thromboembolism -a systematic review and meta-analysis. Issue 4 (October 2015)

• Record Type: Journal Article
• Authors: Sindet-Pedersen, Caroline; Pallisgaard, Jannik Langtved; Olesen, Jonas Bjerring; Gislason, Gunnar Hilmar; Arevalo, Lourdes Cantarero
• Is Part Of: Thrombosis research. Volume 136:Issue 4(2015)
• Page Start: 732
• Page End: 738
• Publication Date: 2015-10
• Subjects: Venous thromboembolism -- New oral anticoagulants -- Vitamin K antagonists -- Recurrent venous thromboembolism -- Bleeding; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2015.07.022
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Objective: To examine and compare the safety and efficacy of extended treatment with dabigatran, apixaban, rivaroxaban and warfarin in patients with unprovoked venous thromboembolism. Methods: PubMed and Embase were searched for randomized clinical trials reporting on the use of direct oral anticoagulants (DOACs) and warfarin for the extended treatment of VTE. Meta-analysis was performed on studies reporting similar study design and comparator. Results: A total of 729 articles were identified and 5 studies covering 6 randomized clinical trials met the eligibility criteria and were included in the study. 5 studies were included in the meta-analysis. Results from the meta-analysis showed that the extended use of DOACs and warfarin significantly decreased the risk of recurrent VTE with 83 % when compared placebo. Warfarin (RR: 0.03, CI: 0.00-0.49) and dabigatran (RR: 0.08, CI: 0.03-0.27) showed the largest relative risk reduction followed by apixaban 2.5 mg (RR: 0.19, CI: 0.11-0.33), rivaroxaban (RR:0.19, CI: 0.09-0.40) and apixaban 5 mg (RR: 0.20, CI: 0.11-0.34). No significant increased risk of major bleeding was observed with the extended use of any DOACs and warfarin compared to placebo (1.15, CI: 0.40-3.31), but an overall increased risk of non-major clinically relevant bleeding (NMCRB) was observed (RR: 2.12, CI: 1.55-2.90). Apixaban 2.5 mg and warfarin was not individually associated with an increased risk of NMCRB. Furthermore, it was found from a study not included in the meta-analysis that dabigatran was non-inferior to VKA for the prevention of recurrent VTE (HR: 1.44, CI: 0.78-2.64, p = 0.01 for noninferiority) and decreased the risk of NMCRB compared to VKA (RR: 0.58, CI: 0.43-0.77). Conclusion: Extended treatment with both warfarin and DOACs are effective in preventing recurrent VTE and does not increase the risk of major bleeding, but increases the risk of NMCRB. Highlights: Safety and efficacy of oral anticoagulants were investigated in a meta-analysis Extended treatment is effective in preventing recurrent venous thromboembolism Extended treatment does not increase the risk of major bleeding Extended treatment increases the risk of non-major clinically relevant bleeding