Daniel Caldeira1, Filipe B Rodrigues2, Márcio Barra2, Ana Teresa Santos2, Daisy de Abreu2, Nilza Gonçalves2, Fausto J Pinto3, Joaquim J Ferreira2, João Costa4. 1. Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Lisbon, Portugal Cardiology Department, Hospital Garcia de Orta, Almada, Portugal Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal. 2. Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Lisbon, Portugal Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal. 3. Cardiology Department, CCUL, CAML, Faculty of Medicine, Lisbon, Portugal. 4. Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Lisbon, Portugal Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal Center for Evidence-Based Medicine, Faculty of Medicine, University of Lisbon, Lisbon, Portugal Portuguese Collaborating Center of the IberoAmerican Cochrane Network, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
Abstract
OBJECTIVE: Non-vitamin K antagonist oral anticoagulants (NOACs) are efficacious and safe antithrombotic drugs but the non-availability of an antidote for potential fatal haemorrhagic events is clinically perceived as a strong limitation. We aimed at evaluating the risk of haemorrhage-related fatalities associated with NOACs in patients requiring long-term anticoagulation. METHODS: MEDLINE, Cochrane Library and Web of Science databases were searched in November 2014 for atrial fibrillation (AF) or venous thromboembolism (VTE) phase III randomised controlled trials (RCT) comparing NOACs with vitamin K antagonists (VKAs) or low molecular weight heparin (LMWH) followed by VKAs. Pooled OR and 95% CIs were estimated through meta-analysis. Heterogeneity was assessed with the I(2) test. RESULTS: Eleven studies were included: 5 on AF and 6 on VTE. A total of 100 324 patients were evaluated in 4 rivaroxaban, 3 dabigatran, 2 apixaban and 2 edoxaban studies. NOAC-treated patients had a 47% odds reduction compared with VKA (OR 0.53; 95% CI 0.42 to 0.68; I(2)=0%; 3 events avoided per 1000 patients) and 64% odds reduction compared with LMWH-VKA (OR 0.36; 95% CI 0.15 to 0.84; I(2)=0%; 1 event avoided per 1000 patients) regarding fatal bleeding risk. Case fatality due to major bleeding was lower in NOAC-treated patients both in AF (OR 0.68; 95% CI 0.48 to 0.96; I(2)=37%; 1 death avoided per 39 major bleedings) and VTE (OR 0.54; 95% CI 0.22 to 1.32; I(2)=0%) patients. AF survivors of major bleeding events treated with NOACs had lower mortality compared with patients treated with VKAs (OR 0.57; 95% CI 0.45 to 0.73; I(2)=0%; 78 events avoided per 1000 survivors to major bleeding). CONCLUSIONS: These data suggest that NOACs decrease the risk of fatality cases related to major bleeding events, particularly in AF patients. These results support the safety profile of NOACs even without having a widely available drug-specific antidote. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
OBJECTIVE: Non-vitamin K antagonist oral anticoagulants (NOACs) are efficacious and safe antithrombotic drugs but the non-availability of an antidote for potential fatal haemorrhagic events is clinically perceived as a strong limitation. We aimed at evaluating the risk of haemorrhage-related fatalities associated with NOACs in patients requiring long-term anticoagulation. METHODS: MEDLINE, Cochrane Library and Web of Science databases were searched in November 2014 for atrial fibrillation (AF) or venous thromboembolism (VTE) phase III randomised controlled trials (RCT) comparing NOACs with vitamin K antagonists (VKAs) or low molecular weight heparin (LMWH) followed by VKAs. Pooled OR and 95% CIs were estimated through meta-analysis. Heterogeneity was assessed with the I(2) test. RESULTS: Eleven studies were included: 5 on AF and 6 on VTE. A total of 100 324 patients were evaluated in 4 rivaroxaban, 3 dabigatran, 2 apixaban and 2 edoxaban studies. NOAC-treated patients had a 47% odds reduction compared with VKA (OR 0.53; 95% CI 0.42 to 0.68; I(2)=0%; 3 events avoided per 1000 patients) and 64% odds reduction compared with LMWH-VKA (OR 0.36; 95% CI 0.15 to 0.84; I(2)=0%; 1 event avoided per 1000 patients) regarding fatal bleeding risk. Case fatality due to major bleeding was lower in NOAC-treated patients both in AF (OR 0.68; 95% CI 0.48 to 0.96; I(2)=37%; 1 death avoided per 39 major bleedings) and VTE (OR 0.54; 95% CI 0.22 to 1.32; I(2)=0%) patients. AF survivors of major bleeding events treated with NOACs had lower mortality compared with patients treated with VKAs (OR 0.57; 95% CI 0.45 to 0.73; I(2)=0%; 78 events avoided per 1000 survivors to major bleeding). CONCLUSIONS: These data suggest that NOACs decrease the risk of fatality cases related to major bleeding events, particularly in AFpatients. These results support the safety profile of NOACs even without having a widely available drug-specific antidote. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Authors: Marc Maegele; Oliver Grottke; Herbert Schöchl; Oliver A Sakowitz; Michael Spannagl; Jürgen Koscielny Journal: Dtsch Arztebl Int Date: 2016-09-05 Impact factor: 5.594