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Objective: Although direct oral anticoagulants (DOAC) are the recommended antithrombotic therapy for patients with non-valvular atrial fibrillation (NVAF), anticoagulation in patients with NVAF is still inadequate. The effect of withholding DOAC therapy on patient survival is unknown. Therefore, our objective was to compare all-cause mortality rates between DOAC-treated patients with NVAF and similar patients receiving no anticoagulation., Methods: We performed a retrospective cohort study analysing Clalit Health Services' extensive electronic database, regarding all newly diagnosed, anticoagulant-naïve patients with NVAF who were eligible for DOAC therapy from 1 January 2011 to 31 December 2016. Patients who received DOAC therapy were matched by propensity scoring to patients receiving no anticoagulation. The primary outcome was all-cause mortality. Final patient follow-up date was 15 May 2017., Results: 18 901 eligible patients were identified. 8298 received treatment with a DOAC and 10 603 received no anticoagulation therapy. Of those, 5657 patients who received DOAC therapy were matched with 5657 patients who did not receive any anticoagulant. Death occurred in 715 patients in the DOAC-treated group (7.6% per year) and in 2075 patients in the non-anticoagulated patient group (11.1% per year). DOAC therapy was associated with significantly lower risk for all-cause mortality (HR=0.69, 95% CI 0.63 to 0.75, p<0.001). The benefit of DOAC therapy was demonstrated across all subgroups analysed., Conclusions: In this cohort of newly diagnosed patients with NVAF, DOAC therapy was associated with a significantly lower risk of death compared with no oral anticoagulation. Our findings provide further evidence for the importance of providing DOAC anticoagulation in patients with NVAF., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Direct oral anticoagulants (DOACs) reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation but may result in serious bleeding complications. Off-label dose-reduced use of DOACs to mitigate bleeding is common in routine clinical practice although data about its consequences on patient outcomes are limited. Therefore, our objective was to evaluate the effectiveness and safety of off-label dose-reduced vs per-label standard-dose DOAC treatment., Methods: The study cohort included newly diagnosed patients with nonvalvular atrial fibrillation that had initiated DOAC therapy between 2011 and 2017 in Clalit Health Services (Tel Aviv, Israel). Effectiveness was defined as the composite outcome of all-cause mortality, stroke, or myocardial infarction. The safety outcome was defined as bleeding events requiring hospitalization. Patients were followed until March 30, 2018 or until occurrence of an outcome event. Hazard ratios (HR) were adjusted for 21 variables, including comorbidities, concomitant medications, and socioeconomic factors, using multivariate regression., Results: A total of 8425 patients met the study criteria; 5140 (61%) patients were treated with DOACs at per-label dosing and 3285 (39%) patients were treated with off-label dose-reduced DOAC. Off-label dose-reduced treatment was associated with a higher rate of the composite effectiveness outcome: adjusted HR 1.57 (95% confidence interval, 1.34-1.83; P < .001) and a higher rate of bleeding: adjusted HR 1.63 (95% confidence interval, 1.14-2.34; P = .008)., Conclusions: Almost 4 of 10 patients were treated with off-label dose-reduced DOAC, which was associated with reduced effectiveness without a safety benefit. Compliance with per-label dosage may significantly improve outcomes of this population., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: The direct oral anticoagulants (DOACs) are a class of drugs used for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and for prevention and treatment of venous thrombo-embolism. They are as effective and are safer than the vitamin K antagonists that were the oral drugs previously used for this purpose. The DOACs are convenient to use because of their fixed dose-response relationship which makes routine monitoring of drug levels unnecessary. Further, they have no food interactions and relatively few drug interactions. A number of practical considerations related to the routine clinical use of the DOACs have become apparent. These include choosing the appropriate drug and importantly dose-based on patient characteristics, managing the use of DOACs peri-operatively and the appropriate management of the acutely bleeding DOAC-treated patient. Recent controlled and observational studies provide guidance for dealing with these clinical situations thus enhancing the efficacy and safety of DOAC treatment in routine clinical practice.