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Efficacy and safety of the drugs used to reverse direct oral anticoagulants: a systematic review and meta‐analysis
Author(s) -
da Luz Luis Teodoro,
Marchand Mylene,
Nascimento Bartolomeu,
Tien Homer,
Nathens Avery,
Shah Prakesh
Publication year - 2017
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.14096
Subject(s) - medicine , meta analysis , confidence interval , cochrane library , randomized controlled trial , dabigatran , idarucizumab , relative risk , clinical trial , medline , clotting factor , warfarin , atrial fibrillation , political science , law
BACKGROUND Direct oral anticoagulants (DOACs) are effective and safe for prophylaxis and treatment of thromboembolic phenomena. However, managing DOACs during bleeding emergencies is challenging. A systematic review and meta‐analysis was conducted on studies addressing efficacy and safety of the drugs used for reversal of DOACs. STUDY DESIGN AND METHODS Medline, Embase, Cochrane Library, and ClinicalTrials.gov were searched up to September 2016. Studies that examined clinical and laboratory effects of drugs used to reverse DOACs were included. Risk of bias was assessed using Newcastle‐Ottawa scale and Cochrane Collaboration tool. Primary and secondary outcomes assessed were reversal of clinical bleeding, clotting assays, and safety, respectively. Overall effect estimates were pooled, and clinical and statistical heterogeneity were assessed. Meta‐analysis was conducted using random‐effects model. RESULTS Four cohort studies in bleeding patients (n = 230) and eight randomized controlled trials in healthy volunteers (n = 381) were included, both with moderate risk of bias. Reversal of clotting assays in healthy volunteers was frequently reported, demonstrating that prothrombin complex concentrate (PCC) reversed prothrombin time (PT) and endogenous thrombin potential (ETP) substantially. For PT, pooled mean difference was 1.68 seconds (95% confidence interval [CI], −0.33 to 3.70 sec; p < 0.01; I 2 = 97%). For ETP, pooled mean difference was 2.16 seconds (95% CI, 0.57 to 3.75 sec; p < 0.01; I 2 = 98%). Andexanet alfa and idarucizumab both reverse clotting assays. No important safety concerns were identified. CONCLUSIONS Clotting assays are partially reversed by PCC in healthy volunteers. Idarucizumab and andexanet alfa have solid laboratory reversal effect and potential to be clinically efficacious and safe. However, clinical evidence is still lacking for all agents.