Clinical and economic benefits of extended treatment with apixaban for the treatment and prevention of recurrent venous thromboembolism in Canada

Abstract

Background and objective Venous thromboembolism (VTE) is associated with long-term clinical and economic burden. Clinical guidelines generally recommend at least 3 months of anticoagulation, but, in clinical practice, concerns over bleeding risk often limit extended treatment. Apixaban was studied for extended VTE treatment in the AMPLIFY-EXT trial, demonstrating superiority to placebo in VTE reduction without increasing risk of major bleeding. This study assessed the long-term clinical and economic benefits of extending treatment with apixaban when clinical equipoise exists compared to standard of care with enoxaparin/warfarin and other novel oral anti-coagulants (NOACs) for the treatment and prevention of recurrent VTE in Canada. Methods A Markov model was developed to follow patients with VTE over their lifetimes. Efficacy and safety for apixaban and enoxaparin/warfarin were based on AMPLIFY and AMPLIFY-EXT, while relative efficacy to other NOACs was synthesized by network meta-analysis (NMA). Dosages for NOACs and enoxaparin/warfarin were based on their respective trials and were given up to 18 months and up to 6 months, followed by no treatment, respectively. Patient quality adjusted life years (QALYs) were based on published studies, and costs for resource utilization were from a Ministry of Health perspective, expressed as 2014 CAD ($). Results Extended treatment with apixaban compared to enoxaparin/warfarin resulted in fewer recurrent VTEs, VTE-related deaths, and bleeding events, but at slightly increased cost. The incremental cost-effectiveness ratio was $4828 per QALY gained. Compared to other NOACs, apixaban had the fewest bleeding events, similar recurrent VTE events, and the lowest overall cost, which was driven by the strong bleeding profile. In scenario analyses of acute and lifetime treatments, apixaban was cost-effective against all strategies. Conclusions Extended treatment with apixaban can offer substantial clinical benefits and is a cost-effective alternative to enoxaparin/warfarin and other NOACs.

Direct Oral Anticoagulants and Vitamin K Antagonists for Treatment of Deep Venous Thrombosis and Pulmonary Embolism in the Outpatient Setting: Comparative Economic Evaluation

“…From a cost perspective, the most important difference between the current study and the existing literature was the application of a pharmaceutical cost of $0.70 per day for VKA, rather than the $0.11 used in previous studies. 28,31 With respect to effectiveness, the current study found that DOACs (most notably apixaban) were more effective at generating QALY relative to LMWH + VKA than was the case in the previous literature. 28,31 This difference probably stems from the assumption in the current This single copy is for your personal, non-commercial use only.…”

“…28,31 With respect to effectiveness, the current study found that DOACs (most notably apixaban) were more effective at generating QALY relative to LMWH + VKA than was the case in the previous literature. 28,31 This difference probably stems from the assumption in the current This single copy is for your personal, non-commercial use only. For permission to reprint multiple copies or to order presentation-ready copies for distribution, contact CJHP at cjhpedit@cshp.ca This single copy is for your personal, non-commercial use only.…”

“…Klarenbach and others 28 compared DOACs with LMWH + VKA and reported that the ICERs associated with DOACs were too high to be considered attractive. Quon and others 31 compared LMWH + dabigatran, rivaroxaban, and LMWH + VKA with apixaban for extended treatment in preventing recurrent VTE and found that apixaban was the dominant strategy for 3-and 6-month durations of anticoagulant therapy and was a cost-effective alternative to LMWH + VKA for 18-month and lifetime durations of anticoagulant therapy.…”

Cost-effectiveness Evaluations Among the Direct Oral Anticoagulants for the Prevention and Treatment of Venous Thromboembolism: Systematic Review

“…28,30,31 Two studies reported results in terms of a number of events among a cohort of 10 000 patients. 27,32 One study reported fatality rates and one study reported relative risk (RR) of recurrent VTE. 26,29 Most articles conducted univariate (1-way) sensitivity analysis to determine the impact of every single parameter used in the analysis model on the total medical cost estimated through the model.…”

“…29 Quon et al concluded that both major and CRNMB events were the main drivers for apixaban being the cost-effective choice among other DOACs. 27 Lanitis et al reported that apixaban…”