Elsevier

Clinical Therapeutics

Volume 36, Issue 10, 1 October 2014, Pages 1389-1394.e4
Clinical Therapeutics

Cost-Utility Analysis of Oral Anticoagulants for Nonvalvular Atrial Fibrillation Patients at the Police General Hospital, Bangkok, Thailand

https://doi.org/10.1016/j.clinthera.2014.08.016Get rights and content

Abstract

Purpose

The genetic polymorphism was one of the major considerations for adjusting doses of warfarin in Thai individuals. As a result, new oral anticoagulants (NOACs) were introduced to achieve therapeutic goals in stroke prevention in atrial fibrillation (SPAF) patients. However, a cost-utility analysis in a population-specific model was lacking in Thailand. This study was performed to determine which NOACs yielded population-specific, cost-effective results for SPAF compared with warfarin from both governmental and societal perspectives in Thailand.

Methods

A simplified Markov health state model was constructed to calculate the lifetime cost, life-years saved, and quality-adjusted life-years (QALYs) gained. Asia-specific clinical event parameters were defined from systematic searches of PubMed. Cost and utility input was obtained from hospital based data collection.

Findings

Although NOACs produced more life-years saved and QALYs gained resulting from the base-case versus warfarin, the lifetime costs of new alternatives increased to >1.4 times the comparative cost of warfarin. This caused an incremental cost-effective ratio that exceeded Thailand’s cost-effectiveness threshold. The probabilistic sensitivity analysis denoted the robustness of our model and revealed that dose-adjusted warfarin was the most cost-effective option in >99% of iterations. NOACs produced cost-effective results when the medication unit cost was decreased by at least 85%.

Implications

According to the results of this first cost-utility analysis in Thailand, warfarin is still the most cost-effective medication for SPAF from any perspective in Thailand at the threshold recommended by our health technology assessment guidelines.

Introduction

Ischemic stroke is the most common thromboembolic complication found in NVAF patients.1 Although the prevalence of nonvalvular atrial fibrillation (NVAF) in Asia is less than half that in the West,2 the risk of thromboembolic events is 2 times higher.3 In particular, neurologic deficits resulting from stroke events leading to family dependence and financial burden represent the most concerning issue. Consequently, the Heart Association of Thailand has issued recommendations on the use of anticoagulants to prevent stroke in moderate- to high-risk patients.2

Even though warfarin, the standard anticoagulant preferred in Thailand, has many advantages (eg, familiar to most physicians, comparatively inexpensive, ability to predict the therapeutic efficacy and safety from the international normalized ratio (INR), availability of the exact antidote),2 the core limitations of its use are interindividual variation including genetic polymorphism, slow onset and offset of action, numerous drug and food interactions, and inconvenience of frequent INR monitoring.4 As a result, new oral anticoagulants (NOACs) were developed to overcome these limitations.5

In Thailand, there are currently 3 NOACs available for stroke prevention in atrial fibrillation (SPAF) that have been approved by the US Food and Drug Administration: 1 is a direct thrombin inhibitor (dabigatran) and 2 are direct factor Xa inhibitors (rivaroxaban and apixaban). Their primary advantages over warfarin are that their thromboembolic preventive effects are at least equal to those of warfarin but with no INR monitoring required.5 Conversely, the budget gain from medical expenses was often realized as a financial burden in Thailand. Finally, there were no population-specific cost-effectiveness studies available, either in Thailand specifically or in Asia in general.

Therefore, this study was conducted to evaluate the cost-utility analysis of NOACs compared with warfarin for SPAF in the Thailand using the Asia-Pacific subgroup analysis parameters from 3 main studies which had been submitted to the US Food and Drug Administration for approval: the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy),6 ROCKET-AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation),7 and ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation).8

Section snippets

Model Structure

A Markov health state model was adapted from related health technology assessment literature9, 10 and reviewed by a cardiologist (Supplemental Figure 1). The model cohorts were patients older than 65 years of age with newly diagnosed NVAF, a moderate to high risk of stroke (CHADS2 score [Congestive heart failure, Hypertension, Age ≥75, Diabetes mellitus, and prior Stroke or transient ischemic attack (doubled)] ≥2), and no history of stroke. Each patient included in the model was assigned to one

Base-Case Analysis

From the base-case analysis, dabigatran 150 mg BID and apixaban 5 mg BID were associated with the highest QALYs gained compared with other anticoagulants (Table I), whereas the warfarin treatment group generated the lowest QALYs gained. Apixaban 5 mg was the most expensive alternative in any perspective. In a subgroup analysis stratified by CHADS2 score, the results of both expected cost and QALYs gained were consistent with the base-case outcomes. According to base-case and subgroup results,

Discussion

This is the first health technology assessment in Thailand that evaluated the cost utility of NOACs compared with warfarin in SPAF by using population-matched parameters. The base-case analysis revealed that warfarin produced higher cost-effectiveness probability than NOACs in any scenario. This is consistent with the findings of the PSA and indicates the robustness of the model.

As far as we know, the findings of this analysis are inconsistent with those of any previously published studies.

Conclusions

According to this analysis, the government-supported medication for SPAF in patients 65 years or age and older with a moderate to high risk of stroke (CHADS2 score ≥2) in Thailand should continue to be treated with warfarin. NOACs were determined as likely to be cost-effective only when their prescription is limited to patients for whom warfarin is unsuitable or if the unit cost of NOACs is reduced by >85%.

Conflicts of Interest

The authors have indicated that they have no conflicts of interest regarding the content of this article.

Acknowledgments

Research question, study design, data collection and analysis was done by first author. The second author responsible in report writing and correspondence. We express our great appreciation to Dr. Yot Teerawattananon and the Health Intervention and Technology Assessment Program team for their guidance and encouragement. We are grateful Dr. Kasem Ratanasumawong, Head of the Department of Medicine, Medical College and Vajira Hospital, Bangkok, Thailand, for reviewing and checking the model.

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