Key result
Standard-dose vitamin-K antagonists and direct oral anticoagulants significantly reduced the risk of recurrent venous thromboembolism compared to aspirin, while sharing similar effects on recurrence and major bleeding with each other.
Why the study?
Extended anticoagulation is preconized in many patients with unprovoked VTE, but limited direct and indirect comparisons exist to weight the benefit/risk ratio of diverse available treatments.
Does extended anticoagulation with VKA, DOAC, or aspirin reduce symptomatic recurrent VTE and major bleeding in patients with previously treated VTE?
Meta-Analysis (n=18,221)
Does extended anticoagulation with VKA, DOAC, or aspirin reduce symptomatic recurrent VTE and major bleeding in patients with previously treated VTE?
Standard-dose VKA and DOACs share similar efficacy for VTE recurrence, but DOACs offer a better safety profile by not significantly increasing major bleeding risk.
Supports DOAC preference for extended VTE anticoagulation; confirms meta-analytic evidence of matched efficacy with superior safety versus VKA.
BACKGROUND: Extended 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. METHODS: A 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. RESULTS: 18 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. CONCLUSION: Standard-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.
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Mai et al. (2019) conducted a meta-analysis in Venous thromboembolism (VTE) (n=18,221). Extended anticoagulation (VKA or DOAC) vs. Aspirin, placebo, or observation was evaluated on Symptomatic recurrent VTE (Standard-dose VKA vs Aspirin) (RR 0.22, 95% CI 0.13-0.39). Standard-dose vitamin-K antagonists and direct oral anticoagulants significantly reduced the risk of recurrent venous thromboembolism compared to aspirin, while sharing similar effects on recurrence and major bleeding with each other.
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