Impact of non-adherence to direct oral anticoagulants amongst Swedish patients with non-valvular atrial fibrillation: results from a real-world cost-utility analysis

Abstract

Aims

A third of non-valvular atrial fibrillation (NVAF) patients are non-adherent to direct oral anticoagulants (DOACs). Estimates of the economic value of full adherence and the cost of two types of adherence improving interventions are important to healthcare planners and decision-makers.

Methods

A cost-utility analysis estimated the impact of non-adherence over a 20-year horizon, for a patient cohort with a mean age of 77 years, based on data from the Stockholm Healthcare database of NVAF patients with incident stroke between 2011 and 2018. Adherence was defined using a medication possession ratio (MPR) cut-off of 90%; primary outcomes were the number of ischemic strokes and associated incremental cost–utility ratio.

Results

Hypothetical comparisons between cohorts of 1,000 patients with varying non-adherence levels and full adherence (MPR >90%) predicted an additional number of strokes ranging from 117 (MPR = 81–90%) to 866 (MPR <60%), and years of life lost ranging from 177 (MPR = 81– 90%) to 1,318 (MPR < 60%; discounted at 3%). Chronic disease co-management intervention occurring during each DOAC prescription renewal and patient education intervention at DOAC initiation will be cost-saving to the health system if its cost is below SEK 143 and SEK 4,655, and cost-effective if below SEK 858 and SEK 28,665, respectively.

Conclusion

Adherence improving interventions for NVAF patients on DOACs such as chronic disease co-management and patient education can be cost-saving and cost-effective, within a range of costs that appear reasonable to the Swedish healthcare system.

PLAIN LANGUAGE SUMMARY

Atrial fibrillation (AF) is the most common type of chronic cardiac arrhythmia and a major risk factor for ischemic stroke (IS). The objective of this study was to compare the costs and health outcomes associated with adherence to direct oral anticoagulant (DOAC) therapy in Sweden. The study also aimed to demonstrate the potential benefits of developing interventions to improve DOAC adherence. DOAC therapy (DOACs; apixaban, dabigatran, edoxaban, and rivaroxaban) has been approved in Europe for the prevention of stroke in adult patients with AF. It has been demonstrated to provide warfarin-similar reductions in stroke risk in NVAF patients, with reductions in mortality and intracranial hemorrhage. However, non-adherence to DOAC medication prevents patients and healthcare systems from fully benefiting from DOAC therapy, resulting in a lower benefit than those seen in randomized controlled trials. DOAC non-adherence is where AF patients deviate from the DOAC treatment regimen as prescribed by health providers. This study suggested that non-adherence to DOAC therapy has a substantial impact on ischemic stroke risk and significant additional healthcare system costs. Patient education and chronic disease co-management (two types of DOAC adherence improving intervention) can be cost-saving and cost-effective within a range of costs that appear reasonable to the Swedish healthcare system. Healthcare policy-makers should prioritize initiatives aimed at improving DOAC adherence in order to improve outcomes in AF.

Keywords:

• Stroke
• atrial fibrillation
• oral anticoagulants
• DOAC
• adherence
• cost-utility

JEL CLASSIFICATION CODES:

• I18
• I1
• I
• H43
• H4
• H
• C54
• C5
• C

Transparency

Declaration of financial/other interests

CBL reports personal fees from Medtronic AB, Boston Scientific, Phillips, Bayer, BMS, MSD, Cathprint, and Aventis, during the conduct of the study. SS reports personal fees from Bayer AB during the conduct of the study. LGR reports grants from Bayer. OA, GJ, and AC are employed by Wickenstones Ltd, a company that received consultancy fees from Bayer. MH, KB, BS, HM, and LH are full-time employees of Bayer. LAL reports grants and personal fees from Bayer and Boehringer Ingelheim, and personal fees from Pfizer, outside the submitted work.

Author contributions

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work, and have given their approval for this version to be published

Acknowledgements

The authors would like to acknowledge James Harris and Peter Maguire (Wickenstones, Carlow, Ireland) for their medical writing assistance during the preparation of the manuscript.

Data availability statement

The data underlying this article are available at https://academic.oup.com/ehjcvp/article/7/FI1/f72/5824225?login=false.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.