Comparative efficacy and safety of anticoagulants and aspirin for extended treatment of venous thromboembolism: A network meta-analysis

Abstract

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT Abstract (305 words)Objective: To systematically review the literature and to quantitatively evaluate the efficacy and safety of extended pharmacologic treatment of venous thromboembolism (VTE) through network meta-analysis (NMA).Methods: A systematic literature search (MEDLINE, Embase, Cochrane CENTRAL, throughSeptember 2014) and searching of reference lists of included studies and relevant reviews was conducted to identify randomized controlled trials of patients who completed initial anticoagulant treatment for VTE and then randomized for the extension study; compared extension of anticoagulant treatment to placebo or active control; and reported at least one outcome of interest (VTE or a composite of major bleeding or clinically relevant non-major bleeding). A random-effects Frequentist approach to NMA was used to calculate relative risks with 95% confidence intervals.Results: Ten trials (n=11,079) were included. Risk of bias (assessed with the Cochrane tool) was low in most domains assessed across the included trials. Apixaban (2.5mg and 5mg), dabigatran, rivaroxaban, idraparinux and vitamin K antagonists (VKA) each significantly reduced the risk of VTE recurrence compared to placebo, ranging from a 73% reduction with idraparinux to 86% with VKAs. With exception of idraparinux, all active therapies significantly reduced VTE recurrence risk versus aspirin, ranging from a 73% reduction with either apixaban 2.5mg or rivaroxaban to 80% with VKAs. Apixaban and aspirin were the only therapies that did not increase composite bleeding risk significantly compared to placebo. All active therapies except aspirin increased risk of composite bleeding by 2 to 4-fold compared to apixaban 2.5mg, with no difference found between the two apixaban doses. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPTConclusion: Extended treatment of VTE is a reasonable approach to provide continued protection from VTE recurrence although bleeding risk is variable across therapeutic options.Our results indicate that apixaban, dabigatran, rivaroxaban, idraparinux and VKAs all reduced VTE recurrence when compared to placebo. Apixaban appears to have a more favorable safety profile compared to other therapies.

Comparison of the Non-VKA Oral Anticoagulants Apixaban, Dabigatran, and Rivaroxaban in the Extended Treatment and Prevention of Venous Thromboembolism: Systematic Review and Network Meta-Analysis

“…Apixaban was reported to be associated with significantly reduced odds of CRNM bleeding compared with both dabigatran and rivaroxaban [ 48 ]. The remaining three NMAs [ 45 – 47 ] were based on more extensive networks including both warfarin [ 45 – 47 ] and aspirin [ 46 , 47 ] and were therefore similar to the network employed in the current analysis. Results from these analyses again confirmed that there was no significant difference between NOACs with regards to the composite outcome of VTE recurrence or all-cause mortality [ 45 – 47 ].…”

Reducing the risk of venous thromboembolism using apixaban – patient perspectives and considerations. Should more attention be given to females?

“…33 Therefore, apixaban has been reported to be an effective and safe alternative to conventional therapy for acute or long-term treatment of VTE and to have a more favorable safety profile compared to other therapies. 34 Moreover, apixaban characteristics were confirmed in patients with mild and moderate renal insufficiency compared to VKAs. 35 NOAs, compared to conventional therapy, represent an economically acceptable strategy for VTE prophylaxis also in surgical patients.…”

Safety of apixaban for venous thromboembolism prophylaxis: the evidence to date

“…The risk with apixaban was also significantly lower than with rivaroxaban, idraparinux, dabigatran, and vitamin K antagonists. 60 Another network meta-analysis including the same 12 trials and an additional trial with ximelagatran vs placebo came to the same conclusion: apixaban 2.5 mg or 5.0 mg was the only treatment that did not increase the risk of major bleeding compared to placebo or observation. The estimated absolute risk difference, presented as a number of major bleeding episodes per 100 patients treated over 1 year, was –0.26 (95% confidence interval –0.32 to 0.2) for apixaban 2.5 mg BID and –0.2 (95% confidence interval –0.3 to 0.6) for apixaban 5.0 mg BID.…”