Extended anticoagulation for the secondary prevention of venous thromboembolic events: An updated network meta-analysis.

Sofia Dias,Vicky Mai,Jean-Christophe Lega,Steeve Provencher,Laurent Bertoletti,Claire Grange,Michel Cucherat,Sabine Jardel

doi:10.1371/journal.pone.0214134

Abstract

BackgroundExtended treatment is preconized in a significant proportion of patients with unprovoked venous thromboembolism (VTE). However, limited direct/indirect comparisons are available to appropriately weight the benefit/risk ratio of the diverse treatments available. We aimed to compare the rate of symptomatic recurrent VTE and major bleeding (MB), the net clinical benefit (VTE+MB) and death on vitamin-K antagonist (VKA), direct oral anticoagulants (DOAC) and antiplatelet drugs for extended anticoagulation.MethodsA systematic literature search through September 2018 identified randomized trials studying these pharmacologic therapies for extended anticoagulation following VTE. Treatment effects were calculated using network meta-analysis with frequentist fixed-effects model.Results18 trials (18,221 patients) were included in the analysis. All treatments reduced the risk of recurrence compared to placebo/observation. Nonetheless, VKA (RR 0.22; 95%CI 0.13–0.39) and DOAC (RRs ranging from 0.25–0.32; 95%CI ranging from 0.13–0.52) were more effective than aspirin, whereas low-dose VKA was less effective than standard-dose VKA (RR 2.47; 95%CI 1.34–4.55). The efficacy of DOAC was globally comparable to standard-adjusted dose VKA. Low- (RR 3.13; 95%CI 1.37–7.16) and standard-dose (RR 3.23; 95%CI 1.16–8.99) VKA also increased the risk of MB, which was not the case for any DOAC. Low-dose VKA and low-dose DOAC had similar effects on MB compared to standard-doses. Although there was a trend for reduced MB and enhanced net clinical benefit for DOAC compared to VKA, this was not statistically significant. The specific anticoagulant therapies had no significant effects on deaths.ConclusionStandard-dose VKA and low/standard-dose DOAC share similar effects on VTE recurrence and MB, whereas aspirin and low-dose VKA were associated with lower benefit/risk ratio.

Highlights

Pulmonary embolism (PE) and deep venous thrombosis (DVT), collectively referred as venous thromboembolism (VTE), are a leading causes of death and disability worldwide, affecting 10 millions of individuals annually [1]
vitamin-K antagonist (VKA) (RR 0.22; 95% confidence interval (95%CI) 0.13– 0.39) and direct oral anticoagulants (DOAC) (RRs ranging from 0.25–0.32; 95%CI ranging from 0.13–0.52) were more effective than aspirin, whereas low-dose VKA was less effective than standard-dose VKA (RR 2.47; 95%CI 1.34–4.55)
Low- (RR 3.13; 95%CI 1.37–7.16) and standard-dose (RR 3.23; 95%CI 1.16–8.99) VKA increased the risk of major bleeding (MB), which was not the case for any DOAC

Summary

Introduction

Pulmonary embolism (PE) and deep venous thrombosis (DVT), collectively referred as venous thromboembolism (VTE), are a leading causes of death and disability worldwide, affecting 10 millions of individuals annually [1]. In patients with acute VTE, anticoagulant therapy markedly decreases the risk of recurrence, at the cost of an increased incidence of bleeding. This risk is varying according to the presence of underlying risk factors and should obviously be balanced with the increased risk of recurrence once anticoagulant therapy is discontinued. Extended treatment is preconized in a significant proportion of patients with unprovoked venous thromboembolism (VTE). We aimed to compare the rate of symptomatic recurrent VTE and major bleeding (MB), the net clinical benefit (VTE+MB) and death on vitamin-K antagonist (VKA), direct oral anticoagulants (DOAC) and antiplatelet drugs for extended anticoagulation

Objectives

Results

Conclusion