Economic evaluation of apixaban for the prevention of stroke in non-valvular atrial fibrillation in the Netherlands

BACKGROUND: Stroke prevention is the main goal of treating patients with atrial fibrillation (AF). Vitamin-K antagonists (VKAs) present an effective treatment in stroke prevention, however, the risk of bleeding and the requirement for regular coagulation monitoring are limiting their use. Apixaban is a novel oral anticoagulant associated with significantly lower hazard rates for stroke, major bleedings and treatment discontinuations, compared to VKAs.OBJECTIVE: To estimate the cost-effectiveness of apixaban compared to VKAs in non-valvular AF patients in the Netherlands.METHODS: Previously published lifetime Markov model using efficacy data from the ARISTOTLE and the AVERROES trial was modified to reflect the use of oral anticoagulants in the Netherlands. Dutch specific costs, baseline population stroke risk and coagulation monitoring levels were incorporated. Univariate, probabilistic sensitivity and scenario analyses on the impact of different coagulation monitoring levels were performed on the incremental cost-effectiveness ratio (ICER).RESULTS: Treatment with apixaban compared to VKAs resulted in an ICER of €10,576 per quality adjusted life year (QALY). Those findings correspond with lower number of strokes and bleedings associated with the use of apixaban compared to VKAs. Univariate sensitivity analyses revealed model sensitivity to the absolute stroke risk with apixaban and treatment discontinuations risks with apixaban and VKAs. The probability that apixaban is cost-effective at a willingness-to-pay threshold of €20,000/QALY was 68%. Results of the scenario analyses on the impact of different coagulation monitoring levels were quite robust.CONCLUSIONS: In patients with non-valvular AF, apixaban is likely to be a cost-effective alternative to VKAs in the Netherlands.</p

Cost-effectiveness acceptability curves for the treatment with apixaban and VKA in non-valvular atrial fibrillation.

<p>The cost-effectiveness acceptability curve assesses the probability that the estimated incremental cost-effectiveness ratio is under a certain willingness to pay threshold. VKA, vitamin-K antagonist; QALY, quality adjusted life year.</p

Stroke and other thromboembolic and bleeding complications and related costs within a hypothetical patient population of 1,000 subjects receiving apixaban and VKA over a lifetime horizon.

<p>VKA, vitamin K-antagonist; p.p., per patient; IS, ischemic stroke; HS, hemorrhagic stroke; SE, systemic embolism; ICH, intracranial hemorrhage; MB, major bleeding; GI, gastrointestinal; CRNM, clinically relevant non-major; MI, myocardial infarction; INR, international normalized ratio.</p

Scenario analyses on the impact of different levels of INR monitoring.

<p>Event rates adjusted for the level of INR monitoring, incremental costs, QALYs and ICERs.</p><p>INR, international normalized ratio; QALY, quality adjusted life year; ICER, incremental cost-effectiveness ratio; IS, ischemic stroke; ICH, intracranial hemorrhage; MB, major bleeding; CRNM, clinically relevant non-major; LY, life-year; cTTR, clinic time in therapeutic range; VKA, vitamin-K antagonist.</p

Transferability of Model-Based Economic Evaluations: The Case of Trastuzumab for the Adjuvant Treatment of HER2-Positive Early Breast Cancer in the Netherlands

AbstractIntroductionGeographic transferability of model-based cost–effectiveness results may facilitate and shorten the reimbursement process of new pharmaceuticals. This study provides a real world example of transferring a cost–effectiveness study of trastuzumab for the adjuvant treatment of HER2-positive early breast cancer from the United Kingdom to The Netherlands.MethodsThree successive steps were taken. Step 1: Collect available information with regard to the original model, and assess transferability using existing checklists. Step 2: Adapt transferability-limiting factors. Step 3: Obtain a country-specific estimate of cost–effectiveness.ResultsThe structure of the UK model was transferable, although some of the model inputs needed adaptation. From a health-care perspective, the Dutch estimate amounted to €5828/quality-adjusted life-year gained. From a societal perspective, the incremental cost–effectiveness ratio was dominant.ConclusionTransferability of a model-based UK-study in three steps proved to be an efficient method to provide an early indication of the cost–effectiveness of trastuzumab and has led to the provisional reimbursement of the treatment

Model for the non-valvular AF population.

<p>Depicted in the diagram are the chance nodes (circles) and terminal nodes (triangles). Branches for apixaban and VKA are identical except numerical risks. Patients that discontinue the initial anticoagulant treatment re-enter the model with identical Markov branches but under the assumption of switching their treatment to acetylsalicylic acid. NVAF, non-valvular atrial fibrillation; ASA, acetylsalicylic acid; IS, ischemic stroke; HS, hemorrhagic stroke; SE, systemic embolism; MI, myocardial infarction; ICH, intracranial hemorrhage; CRNM, clinically-relevant non-major; MB, major bleeding; Tmt, treatment.</p

Tornado diagram illustrating results from sensitivity analyses for apixaban vs. vitamin-K antagonists.

<p>Black bars denote influence of the high value of the 95% confidence interval range and grey bars denote influence of the low value for parameters investigated. ICER, incremental cost-effectiveness ratio; QALY, quality adjusted life year; ICH, intracranial hemorrhage; AF, atrial fibrillation; MI, myocardial infarction; MB, major bleeding.</p

Incremental costs, QALYs and ICER for patients with non-valvular AF receiving anticoagulation therapy.

<p>QALY, quality adjusted life year; AF, atrial fibrillation; LY, life-year; ICER, incremental cost-effectiveness ratio; VKA, vitamin-K antagonist.</p