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Chest. 2019 Jun;155(6):1199-1216. doi: 10.1016/j.chest.2019.02.402.

Extended Anticoagulation for VTE: A Systematic Review and Meta-Analysis.

Author information

1
Institut universitaire de cardiologie et de pneumologie de Québec Research Center, Laval University, Québec City, QC, Canada.
2
Institut universitaire de cardiologie et de pneumologie de Québec Research Center, Laval University, Québec City, QC, Canada; Department of Medicine, Université Laval, Québec City, QC, Canada; Pulmonary Hypertension Research Group.
3
Service de Médecine Vasculaire et Thérapeutique, CHU de St-Etienne, Saint-Étienne, France; Université Jean-Monnet, UMR 1059, SAINBIOSE, Saint-Étienne, France; INSERM CIC 1408, Saint-Étienne, France; Groupe d'Etude Multidisciplinaire des Maladies Thrombotiques (GEMMAT), Hospices Civils de Lyon, Lyon, France; University of Lyon, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, CNRS, Villeurbanne, France.
4
Institut universitaire de cardiologie et de pneumologie de Québec Research Center, Laval University, Québec City, QC, Canada; Department of Medicine, Université Laval, Québec City, QC, Canada.
5
Groupe d'Etude Multidisciplinaire des Maladies Thrombotiques (GEMMAT), Hospices Civils de Lyon, Lyon, France; University of Lyon, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, CNRS, Villeurbanne, France; Department of Internal and Vascular Medicine, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, F-69310, Pierre-Bénite, France.
6
Institut universitaire de cardiologie et de pneumologie de Québec Research Center, Laval University, Québec City, QC, Canada; Department of Medicine, Université Laval, Québec City, QC, Canada; Pulmonary Hypertension Research Group. Electronic address: steve.provencher@criucpq.ulaval.ca.

Abstract

BACKGROUND:

The efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) during extended anticoagulation for a VTE remains largely unknown, especially in terms of potential survival benefit. The goal of this study was to assess the effects of VKAs and DOACs on overall mortality and VTE-related mortality, as well as VTE recurrence and safety.

METHODS:

PubMed, EMBASE, and the Cochrane Library were searched from January 1990 through September 2018 for randomized controlled trials evaluating the effect of extended anticoagulants as secondary prevention for VTE compared with placebo. The primary outcome was the specific effects of standard-intensity VKAs and DOACs on overall mortality.

RESULTS:

Sixteen studies (12,458 patients) were included. DOACs were associated with a reduction in overall (risk ratio [RR], 0.48; 95% CI, 0.27-0.86; P = .01) and VTE-related (RR, 0.36; 95% CI, 0.15-0.89; P = .03) mortality, whereas VKAs were not (P > .50). Although VKAs and DOACs similarly prevented recurrent VTE, only VKAs were associated with an increased risk of major bleeding (RR, 2.67; 95% CI, 1.28-5.60; P < .01), resulting in an improved net clinical benefit for DOACs (RR, 0.25 [95% CI, 0.16-0.39; P < .01] vs 0.46 [95% CI, 0.30-0.72; P < .01]; Pinteraction = .05).

CONCLUSIONS:

DOACs for extended anticoagulation were associated with a significant reduction in overall mortality compared with observation alone.

TRIAL REGISTRY:

PROSPERO; No.: CRD42018088739; URL: https://www.crd.york.ac.uk/prospero/.

KEYWORDS:

VTE; direct oral anticoagulant; extended anticoagulation; mortality; vitamin K antagonist

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