Directly Acting Oral Anticoagulants for the Prevention of Stroke in Atrial Fibrillation in England and Wales: Cost-Effectiveness Model and Value of Information Analysis

Abstract

Objectives. Determine the optimal, licensed, first-line anticoagulant for prevention of ischemic stroke in patients with non-valvular atrial fibrillation (AF) in England and Wales from the UK National Health Service (NHS) perspective and estimate value to decision making of further research. Methods. We developed a cost-effectiveness model to compare warfarin (international normalized ratio target range 2–3) with directly acting (or non–vitamin K antagonist) oral anticoagulants (DOACs) apixaban 5 mg, dabigatran 150 mg, edoxaban 60 mg, and rivaroxaban 20 mg, over 30 years post treatment initiation. In addition to death, the 17-state Markov model included the events stroke, bleed, myocardial infarction, and intracranial hemorrhage. Input parameters were informed by systematic literature reviews and network meta-analysis. Expected value of perfect information (EVPI) and expected value of partial perfect information (EVPPI) were estimated to provide an upper bound on value of further research. Results. At willingness-to-pay threshold £20,000, all DOACs have positive expected incremental net benefit compared to warfarin, suggesting they are likely cost-effective. Apixaban has highest expected incremental net benefit (£7533), followed by dabigatran (£6365), rivaroxaban (£5279), and edoxaban (£5212). There was considerable uncertainty as to the optimal DOAC, with the probability apixaban has highest net benefit only 60%. Total estimated population EVPI was £17.94 million (17.85 million, 18.03 million), with relative effect between apixaban versus dabigatran making the largest contribution with EVPPI of £7.95 million (7.66 million, 8.24 million). Conclusions. At willingness-to-pay threshold £20,000, all DOACs have higher expected net benefit than warfarin but there is considerable uncertainty between the DOACs. Apixaban had the highest expected net benefit and greatest probability of having highest net benefit, but there is considerable uncertainty between DOACs. A head-to-head apixaban versus dabigatran trial may be of value.

Cost-Effectiveness Analysis of Direct Oral Anticoagulants Vs. Vitamin K Antagonists in the Elderly With Atrial Fibrillation: Insights From the Evidence in a Real-World Setting

“…The comparison of DOACs vs. warfarin in AF has been discussed frequently. Owing to their impressive efficacy and convincing safety profiles reported by RCTs, the economic viability of DOACs has been demonstrated in the US ( 9 , 28 ), European countries ( 10 , 11 ), and in some Asian countries ( 17 , 38 , 39 ). Despite their much higher costs, DOACs are generally more cost-effective than warfarin.…”

“…Owing to their efficacy profiles, which have been recently reported by several large, randomized controlled trials (RCTs), direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, apixaban, and edoxaban, are viable alternatives for VKAs and have been established as cornerstones in AF management for the prevention of stroke (7,8). Based on the results of a meta-analysis of RCTs, DOACs have been reported to be more cost-effective than VKAs (9)(10)(11). However, since no RCT was designed to focus on the elderly population specifically, there is little clarity regarding the health and economic benefits of DOACs in the said population (12).…”

Uptake of direct oral anticoagulants in primary care: an ecological and economic study

“…11 A recent systematic review of all RCT data found that all DOACs had a higher expected net benefit than warfarin, at a willingness to pay threshold of £20 000 per quality adjusted life year. 29 This apparent discrepancy may reflect a blunting of DOAC effectiveness in real-world practice, as well as the study's inability to capture the cost to patients and impact on quality of life. Indeed, evidence indicates that patients receiving DOACs report better quality of life scores and lower levels of depression, compared with patients on warfarin.…”

Multilevel and Quasi Monte Carlo methods for the calculation of the Expected Value of Partial Perfect Information

“…Firstly it may require a very large number of samples to characterise the posterior distribution, for example if correlations between parameters impede mixing of the sampler. In addition to needing a large number of samples, it can also be computationally expensive to generate each sample from the posterior, as for the NMA used in the directly acting oral anticoagulants (DOACs) for prevention of stroke in atrial fibrillation Markov model [15, 16, 17, 18]. This can make nested Monte Carlo, or the generation of a sufficient number of samples to determine the regression function for GAM or GP methods, impractical.…”

“…Section 4 presents an application to an artificial, but realistic, decision tree depression model with MCMC input parameters. Section 5 presents an application to the published and highly complex DOACs for prevention of stroke in atrial fibrillation Markov model [16, 17, 18]. Further discussions and conclusions are provided in Section 6.…”