Cost-effectiveness of dabigatran for thromboembolic events prevention in atrial fibrillation patients in Chile

Abstract

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia in adults, associated with significant morbidity, mortality, and economic burden due to thromboembolic events. In Chile, acenocoumarol is the most widely used anticoagulant, while access to direct oral anticoagulants (DOACs) such as dabigatran, rivaroxaban, and apixaban remains limited for AF patients. Among DOACs, dabigatran is the only one with an approved specific reversal agent (idarucizumab) available in the Chilean public system. Evaluating the cost-effectiveness of these alternatives is critical for informing resource allocation.

Aims: To evaluate the cost-effectiveness of dabigatran compared to acenocoumarol, rivaroxaban and apixaban, for thromboembolic events prevention in atrial fibrillation (AF) patients, from the Chilean public health payer perspective.

Methods: A Markov cohort model was used to represent the natural history of AF in terms of ischemic and hemorrhagic complications. Direct costs were obtained from local official sources and converted to US dollars (1 USD = 710.9 CLP at 2022). Data about major events and utilities were obtained from the literature. We applied an undifferentiated discount rate of 3% for costs and outcomes over a lifetime time horizon. Uncertainty was characterized through deterministic and probabilistic sensitivity analysis. We also examined the use of idarucizumab and prothrombin-complexes-concentrate (PCC) as reversal agents in an emergency setting as an additional scenario-analysis.

Results: Dabigatran was the most (cost-)effective among all alternatives (8.53 QALYs). Considering the Chilean cost-effectiveness threshold of USD 17,200 (1 GDP per capita), dabigatran was cost-effective (USD 11,042 per QALY gained), while both rivaroxaban and apixaban were dominated by dabigatran. Regarding the second-order uncertainty, at the suggested threshold, dabigatran exhibit the highest probability of being cost-effective (approximately 60%). In the reversal agent scenario, dabigatran plus idarucizumab was also found to be cost-effective in the Chilean context.

Conclusion: Dabigatran is cost-effective and dominates both rivaroxaban and apixaban at current publicly available prices in Chile. In addition, we expect dabigatran-idarucizumab is also expected to be cost-effective for Chilean health system when is compared against acenocoumarol-PCC as reversal agents.

Keywords: Atrial fibrillation; Cost-effectiveness; Dabigatran; Thromboembolic events.

Fig. 1

Markov model structure. IS: Ischemic Stroke. ICH: Intracranial hemorrhage. ECH: Extracranial hemorrhage. SE: Systemic embolism. TIA: Transient ischemic attack. MI: Myocardial Infarction. a: Individuals in treatment may be under first and second line treatment. Transition to second-line treatment is determined by safety issues non-related to major events occurrence (adverse events). b: Main events recorded by the model, which could generate a degree of disability or treatment interruption. The direction of the arrow informs the potential impact on patient disability and treatment status — Patients who suffer an ICH are assumed to discontinue treatment. c: Major events that do not result in disability or treatment interruption

Fig. 2

Reversal agent scenario. p: Represents the capability of the reversal agent to prevent the disabilities associated with the onset of ICH. For this scenario analysis, multiple efficacy values for p (p = 1, 0.75, 0.5, 0.25, and 0.1) will be evaluated, ranging from the most optimistic possible scenario ─ the reversal agent prevents the outcome of total disability in 100% of patients─ to a very conservative scenario, the reversal agent prevents the outcome of total disability in only 10% of patients

Fig. 3

Cost-effectiveness analysis acceptability curve