With improvements in the rhythm control treatment of atrial fibrillation (AF), beneficial effects on cardiovascular (CV) outcomes have been shown in AF patients who received active rhythm control (1–3). Based on the latest available data from a national survey, the prevalence of AF in the Republic of Korea is increasing, and the proportion of patients at high risk for stroke or heart failure (HF) has been rising because of its prevalence in the aging society (4–6). The cost of disease burden is also increasing with AF-related complications in both in-hospital and outpatient clinic settings (4, 7).

Previous studies have revealed that ablation-based rhythm control of AF is associated with lower AF recurrences, prolonged time in sinus rhythm, and improved quality of life (8–11). In a trial of ablation vs. medical therapy in symptomatic patients with AF and HF, successful ablation could extend survival and reduce HF admission (12). Real-world studies have reported favorable outcomes, such as reduced ischemic stroke and death in ablated patients (13–16). It can be hypothesized that ablation-based rhythm control of AF is related to economic benefit. In some countries, economic assessments have reported a good cost-saving in ablation-based therapy compared with medical therapy (17, 18). However, the economic evaluation of different rhythm control strategies for treating AF has not been conducted in the Republic of Korea. Additional costs of drugs and ablation procedures, hospitalization, and reimbursement systems can impact economic assessment results (19). To provide acceptable economic value beyond clinical benefit (2, 3), we evaluated the cost-effectiveness of ablation-based and antiarrhythmic drugs (AADs)-based rhythm control therapies for patients with drug-refractory AF from a nationwide real-world cohort in the Republic of Korea.

This study is based on the National Health Insurance (NHI) claims database established by the Health Insurance Review and Assessment Service (HIRA) of the Republic of Korea (4–6, 20, 21). The NHI service (NHIS) is the single insurer controlled by the Korean government, and the majority (97.1%) of Korean population are its mandatory subscribers, with the remaining 3% of the population being medical aid subjects. The HIRA service is a value-based purchasing system for medical service quality improvement that provides a review of incurred medical costs and reports from healthcare providers about medical services performed for HIRA. These databases include the following: medical aid subjects, sociodemographic information of patients, their use of inpatient and outpatient services, procedure and procedure-related resource use, pharmacy dispensing claims, disease information, and mortality of the entire Korean population. This study was approved by the Institutional Review Board of the Kyung Hee University Health System (2020-05-040), and the requirement for informed consent was waived.

The results of our analysis provide real-world population-based evidence confirming that choosing ablation-based, rather than AADs-based, rhythm control therapy in Korean patients with AF produces extra QALYs at a cost that meets current criteria for a good value in healthcare. Deterministic and PSA also revealed that ablation-based therapy was more cost-effective when using different parameter values, except for the costs of hospitalization/unplanned visits for HF and bootstrap uncertainty analysis. These findings support the economic benefit of ablation-based therapy along with an improvement in the clinical outcomes compared with AADs-based therapy.

Despite advances in ablation and procedure techniques, cost-effectiveness analyses of ablation-based rhythm control therapy have yielded heterogeneous conclusion that depend on the analysis model, parameters derived from the literature, and study population (17, 18, 35–39). Recently, Chew et al. (18) reported randomized trial-based economic evaluation results suggesting that catheter ablation of AF is economically attractive compared with drug therapy with an ICER of $57,893/QALY using the conventional WTP threshold of $100,000/QALY in the US. This study included detailed and comprehensive resource use data and quality-of-life adjustment factors. Patients assigned to the ablation group had significantly higher costs attributed to the initial cost of the procedure compared with the AADs group in the first 3-months of follow-up; no significant difference in costs was observed beyond 1 year suggesting the long-term economic benefits of ablation.

Leung et al. (17) reported the comparison of cost-effectiveness of catheter ablation and medical therapy using the National Health Service data in the United Kingdom. The authors concluded that their base case ICER was favorable for ablation-based therapy with a highly significant decrease in CV events and AF recurrences, despite a higher up-front cost for the procedure. These two studies also evaluated the cost-effectiveness of pre-specified subgroups of patients with HF. In both the studies, compared with the base case analysis, the value of ablation-based rhythm control was particularly attractive in the HF group based on greater quality-of-life gains.

With a view of negative cost-saving, Reynolds et al. (37) found that the cost-effectiveness of cryoballoon ablation, compared with AADs, has an ICER value greater than the WTP threshold in the UK. A study conducted in Australia by Gao et al. (36) reported the cost-effectiveness of catheter ablation vs. medical therapy in patients with AF and HF, yielding an ICER above the WTP threshold. However, these two study groups did not consider detailed CV outcomes, such as hospitalization for HF, stroke, and bleeding, which impact the costs and quality of life.

The periprocedural transient ischemic attack (TIA) or ischemic stroke rate was 4.13%/year in our population. This finding appears to be high compared to the majority of studies available from literature (22, 40, 41). The difference might have originated from definition of the periprocedural complications. We defined the periprocedural TIA or ischemic stroke based on hospital discharge diagnoses and the presence of brain imaging codes. The possibility of overestimation cannot be excluded because of the asymptomatic embolic events that showed a high incidence after AF ablation in previous study (42). Recent meta-analysis reported that the incidence of silent cerebral embolism after AF ablation ranged from 10 to 24%, respectively (43). These are considered potential reasons.

Our study evaluated the economic attractiveness of ablation-based and AADs-based rhythm control therapies for treating AF using comprehensive and detailed parameters in a real-world population. Our results support the greater cost-saving ability of ablation-based therapy compared with AADs-based therapy. Additionally, as shown in the previous studies and our study, ablation-based therapy is safe, with low rates of complications and mortality. These results are consistent with the outcomes of the sensitivity analyses.

Several limitations should be acknowledged when interpreting the results of this study. First, because details of rhythm status were not available, we did not consider rhythm status in the model structure. However, we included patients in the antiarrhythmic drug therapy group who had an MPR ≥ 80%, assuming good rhythm control status. Second, repeat procedures and same day discharge after procedure were not considered in the model. In the clinical era, it is possible that patients may experience repeated ablations, and the cost of these procedures may vary from that of the index ablation. In Korea, it is uncommon to discharge same day after AF ablation. These could have resulted in the underestimation of the difference in costs between the two groups. Third, our results are derived from an on-treatment design that does not allow crossover between arms, which frequently occurs. We also analyzed specific subset of population who had no previous health events and <75 years. Therefore, this study may not accurately reflect situations commonly encountered in clinical practice. Fourth, we analyzed the health events of hospitalization/unplanned visits for HF, MI, ischemic stroke, ICH, GI bleeding, and mortality over 3 years; however, this duration does not fully reflect the rest of the patient’s life. Fifth, the utility of periprocedural TIA was equal to that of periprocedural strokes; however, the actual utility of periprocedural TIA may be better than that of the periprocedural strokes. Therefore, the QALY value of the ablation group may have been underestimated. Sixth, the model parameters and clinical event rates were derived from a country-based population and reimbursement system. From a generalizability perspective, our findings may not be applicable to a global region. Finally, the ablation-based rhythm control therapy included different ablation techniques, i.e., cryoballoon ablation and radiofrequency catheter ablation, and the cost-effectiveness of the different ablation techniques is indistinguishable in the analyses. Owing to a low number of cryoballoon ablations (3.43%), additional analyses were not considered. The different costs of the different tools, such as radiofrequency with different mapping systems and ablation/mapping catheters, cryoballoon, could potentially grow the costs of ablation and will become even more important with upcoming pulsed-field ablation therapies.

Based on the real-world economic evaluation, ablation-based rhythm control therapy for treating AF under the age of 75 years is a cost-effective therapeutic option compared with the antiarrhythmic drugs-based therapy, with an incremental cost-effectiveness ratio of $7,913/QALY. This result was consistent regardless of the stroke risk and presence of HF.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

This study was approved by the Institutional Review Board of the Kyung Hee University Health System (2020-05-040), and the requirement for informed consent was waived. The ethics committee waived the requirement of written informed consent for participation.

BJ, MK, and WK: conceptualization and writing—original draft. YK: data curation. WK and YK: formal analysis. BJ and J-BK: funding acquisition and project administration. BJ, MK, WK, and YK: investigation. WK, MK, J-BK, CK, and BJ: methodology. WK, YK, and WP: resources. CK, BJ, MK, WK, and WP: software. CK and BJ: supervision. CK, BJ, MK, and WK: validation, visualization, and writing—review and editing. All authors contributed to the article and approved the submitted version.