Cost-effectiveness of digoxin versus beta blockers in permanent atrial fibrillation: the Rate Control Therapy Evaluation in Permanent Atrial Fibrillation (RATE-AF) randomised trial

Abstract

Background: Atrial fibrillation (AF) is a major and increasing burden on health services. This study aimed to evaluate the cost-effectiveness of digoxin versus beta-blockers for heart rate control in patients with permanent AF and symptoms of heart failure.

Methods: RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) was a randomised, open-label, blinded, endpoint trial embedded in the UK National Health Service (NHS) to directly compare low-dose digoxin with beta-blockers (ClinicalTrials.gov: NCT02391337). A trial-based cost-utility analysis was performed from a healthcare perspective over 12 months. Resource use in primary and secondary healthcare services, medications and patient-reported quality of life were prospectively collected to estimate differences in costs and quality-adjusted life years (QALYs).

Results: RATE-AF randomised 160 patients with mean age of 76 (SD 8) years and 46% women, of which 149 patients (n=73 digoxin, n=76 beta blockers) had complete data and survived to 12-month follow-up. Treatment with digoxin was significantly less costly, with a mean saving of £530.41 per patient per year (95% CI -£848.06 to -£249.38, p=0.001). This was principally due to substantially lower rates of adverse events, with less primary and secondary healthcare utilisation compared with beta-blocker therapy. There was no significant difference in QALYs (0.013; 95% CI -0.033 to 0.052, p=0.56). At the £20 000 per-QALY willingness to pay threshold, the probability of digoxin being cost-effective compared with beta-blockers was 94%, with potential annual savings to the NHS of £102 million/year (95% CI £48 million to £164 million saving, p=0.001).

Conclusions: Digoxin is a less costly option when compared with beta-blockers for control of heart rate in suitable patients with permanent AF, with larger cost-effectiveness studies warranted to advise on national and global policy-making.

Trial registration number: NCT02391337, EudraCT 2015-005043-13.

Keywords: Atrial Fibrillation; Health Care Economics and Organizations; Quality of Health Care.

Figure 1. RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial adverse outcomes for digoxin versus beta-blockers. Events recorded for the 12-month follow-up period in patients randomised to digoxin or beta-blockers. Serious adverse events and cardiovascular events were independently adjudicated. *A prespecified statistical analysis was performed for adverse treatment events (p<0.001). AF, atrial fibrillation; CV, cardiovascular.

Figure 2. Cost-effectiveness plane for digoxin versus beta-blockers. Adjusted differences in costs and quality-adjusted life years (QALYs) from the UK National Health Service perspective over a 12-month period.

Figure 3. Cost-effectiveness acceptability curve. Indicates the probability of digoxin being cost-effective compared to beta-blockers across different willingness-to-pay thresholds per additional quality-adjusted life year (QALY) at 12 months from the UK National Health Service perspective.