Dabigatran etexilate versus warfarin in management of non-valvular atrial fibrillation in UK context: quantitative benefit-harm and economic analyses

Abstract

Objectives To determine the incremental net health benefits of dabigatran etexilate 110 mg and 150 mg twice daily and warfarin in patients with non-valvular atrial fibrillation and to estimate the cost effectiveness of dabigatran in the United Kingdom.Design Quantitative benefit-harm and economic analyses using a discrete event simulation model to extrapolate the findings of the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) study to a lifetime horizon.Setting UK National Health Service.Population Cohorts of 50 000 simulated patients at moderate to high risk of stroke with a mean baseline CHADS2 (Congestive heart failure, Hypertension, Age≥75 years, Diabetes mellitus, previous Stroke/transient ischaemic attack) score of 2.1.Main outcome measures Quality adjusted life years (QALYs) gained and incremental cost per QALY of dabigatran compared with warfarin.Results Compared with warfarin, low dose and high dose dabigatran were associated with positive incremental net benefits of 0.094 (95% central range −0.083 to 0.267) and 0.146 (−0.029 to 0.322) QALYs. Positive incremental net benefits resulted for high dose dabigatran in 94% of simulations versus warfarin and in 76% of those versus low dose dabigatran. In the economic analysis, high dose dabigatran dominated the low dose, had an incremental cost effectiveness ratio of £23 082 (€26 700; $35 800) per QALY gained versus warfarin, and was more cost effective in patients with a baseline CHADS2 score of 3 or above. However, at centres that achieved good control of international normalised ratio, such as those in the UK, dabigatran 150 mg was not cost effective, at £42 386 per QALY gained.Conclusions This analysis supports regulatory decisions that dabigatran offers a positive benefit to harm ratio when compared with warfarin. However, no subgroup for which dabigatran 110 mg offered any clinical or economic advantage over 150 mg was identified. High dose dabigatran will be cost effective only forpatients at increased risk of stroke or for whom international normalised ratio is likely to be less well controlled.

Nonvitamin-K-Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and Previous Stroke or Transient Ischemic Attack

“…Furthermore, at present there is no specific antidote for patients who require an immediate reversal of their effect, but for dabigatran and apixaban antidotes are in development. Also, non-VKAs have a significantly higher cost than warfarin 11 ; however, several studies have shown that they are cost-effective not only for primary stroke prevention [12][13][14][15] but also for secondary stroke prevention. 16 Finally, non-VKAs are mainly excreted via kidneys and therefore their use should be cautious in patients with renal insufficiency.…”

Cost-Effectiveness of Apixaban, Dabigatran, Rivaroxaban, and Warfarin for Stroke Prevention in Atrial Fibrillation

“…11,13 Although INR control is a determinant of the cost-effectiveness of dabigatran in studies conducted in the United States and United Kingdom, INR management in real-world populations varies, and the time in therapeutic range for patients receiving warfarin is highly variable. [11][12][13]37 A number of studies have estimated that patients spend from 41% to 72% of their time in the recommended INR range for warfarin. [38][39][40] Clinical trials for NOACs report time in therapeutic range values within this range, and therefore, INR was not incorporated as a model parameter in this study.…”

Using simulation and optimization approach to improve outcome through warfarin precision treatment

“…Many clinical trial simulations (CTS) were used to access cost-effectiveness 19 , health economic 20 , and discrete-event 19,21 . Some studies apply CTS to help understand how different genotypes influence dosing decisions 22 .…”