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

Abstract

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.

• Authors: Vicky Mai, Laurent Bertoletti, Michel Cucherat, Sabine Jardel, Claire Grange, Steeve Provencher, Jean-Christophe Lega
• Journal: PloS one (PLoS One) Vol. 14 Issue 4 Pg. e0214134 ( 2019) ISSN: 1932-6203 [Electronic] United States
• PMID: 30933993 (Publication Type: Journal Article, Meta-Analysis)

Chemical References

• Anticoagulants
• Heparin, Low-Molecular-Weight
• Platelet Aggregation Inhibitors
• Vitamin K
• Warfarin
• Aspirin

Topics

• Administration, Oral
• Anticoagulants (therapeutic use)
• Aspirin (adverse effects, therapeutic use)
• Blood Coagulation (drug effects)
• Female
• Hemorrhage (drug therapy, pathology)
• Heparin, Low-Molecular-Weight (adverse effects, therapeutic use)
• Humans
• Male
• Network Meta-Analysis
• Platelet Aggregation Inhibitors (adverse effects, therapeutic use)
• Secondary Prevention
• Venous Thromboembolism (blood, pathology, prevention & control)
• Venous Thrombosis (blood, pathology, prevention & control)
• Vitamin K (antagonists & inhibitors)
• Warfarin (adverse effects, therapeutic use)