5.1 Overview of findings

The current study presents a cost-effectiveness analysis conducted to determine if ablation is more cost-effective than medical therapy for the treatment of AF. The base case analysis considered the cost of state-of-the-art radiofrequency ablation and followed patients over the remainder of their life.

The findings of this study support catheter ablation as a highly cost-effective strategy for patients suffering from AF, compared to medical therapy. Despite a higher up-front cost for the ablation procedure, a highly significant decrease in CV adverse events and AF recurrence during follow-up led to an ICER of £8614, which is well below the current WTP threshold of £20 000. Not only was ablation highly cost-effective when evaluating patients over their lifetime—catheter ablation also remained cost-effective at time horizons of 10, 15, and 20 years.

With ablation having an improved efficacy in patients with concomitant AF and HF, the scenario analysis performed on this population showed catheter ablation treatment to be more cost-effective than in both the base case analysis and the scenario evaluating non-HF patients.

5.1.1 AF subtypes and first line treatment

There is public interest and debate over the potential benefits and cost-effectiveness of catheter ablation versus medical therapy, particularly in patients with persistent AF. This study examined patients with all types of AF and did not specifically break out or model patients with paroxysmal versus persistent AF, using population level treatment effects that were applicable to all AF subtypes. This was done for two reasons—first, by evaluating all AF patients, it gives a more comprehensive view of the real-world cost-effectiveness of ablation to inform policy and reimbursement decisions. Second, there is a lack of direct published evidence, particularly in real-world studies, comparing catheter ablation to medical therapy in persistent AF. As more evidence becomes available, it will be important to conduct future health economic research on the sub-types of AF. The same limitations apply to questions surrounding the health and economic benefits associated with first line treatment of AF.

5.1.2 Comparison with existing literature

In April 2021, NICE published the results of their cost-effectiveness analysis comparing AADs to seven different types of ablation technology including RF point by point (PP) and cryoballoon ablation over a lifetime horizon.14 In that analysis, RF PP ablation was found to be the most cost-effective option, with an ICER of £9764 per QALY gained. The study by NICE only utilized data published from clinical trials to populate utilization parameters and drive the analysis. In contrast, the current study presented here used real-world data with large sample sizes to estimate utilization. Our findings confirm the those of NICE in a real-world setting, providing support for the conclusion that RF ablation is a more cost-effective treatment option than medical therapy.

A challenge with both our model and the NICE ablation cost-effectiveness analysis is that the clinical evidence includes ablation technology that is no longer considered standard of care. The AF recurrence network meta-analysis NICE performed identified 16 studies that included RF PP technology; however, only 4/16 studies included contact force sensing technology. Contact force sensing technology is considered to be a significant improvement upon older technology.40-44 A recent network meta-analysis (Gupta 2020) found increased freedom from AF in the latest generations of RF technology compared to noncontact force sensing. Our model included the costs of state-of-the-art radiofrequency ablation, but not the clinical outcomes, thus in reality, the cost-effectiveness of ablation may be further improved.

Beyond the NICE analysis, a 2014 study by Reynolds et al.13 compared the cost-effectiveness of cryoballoon ablation to antiarrhythmic drugs in the UK found an ICER of £21 957, which was above the WTP threshold. The Reynolds study only looked at a time-horizon of 5 years and did not consider events such as HF hospitalizations, which may explain the higher ICER. Additionally, the catheter costs used in this current study are reflective of state-of-the-art radiofrequency catheters, as opposed to older generation cryoballoon catheters. The AF recurrence data in this study are predominantly from radiofrequency ablation studies although it was not possible to determine the technology used in the CABANA study which has the heaviest weighting in the meta-analysis.

A study performed in Australia by Gao and Moodie27 looked at the cost-effectiveness of catheter ablation versus medical therapy in patients with both AF and HF, yielding an ICER that was above the WTP threshold. However, the study outcome was only evaluated on the impact of reduced mortality. Therefore, healthcare facility utilization and other clinical events were not accounted for, which are important variables with significant impact on cost and quality of life.

Another important distinction between this study and many of the previously published cost-effectiveness studies was the use of real-world evidence.10, 13, 27 Clinical trials often have protocols that influence utilization, are performed at the top-performing high-volume clinical sites, and generally have relatively small sample sizes. By using large real-world populations to derive many of the estimates used in this model, the results become more generalizable and can capture benefits that may not be seen in smaller, randomized trials. This approach may become more widespread due to NICE announcing more routine use of real-world data as part of their 5-year strategy launched April 2021.

5.1.3 Implications for healthcare providers and resource allocation

This is the first comprehensive economic evaluation of catheter ablation compared with medical therapy for the treatment of AF in the UK that utilizes real world data. This study now confirms that in addition to clinical effectiveness, ablation is expected to be cost effective in the long-term even with the inclusion of cost data associated with state-of-the-art radiofrequency technology. As shown in other studies, our systematic review and meta-analysis confirmed that ablation is safe with low rates of complications with reduction in CV adverse events. This evidence, when taken together, suggests that healthcare providers should prioritize investment in arrhythmia services where catheter ablation treatment is available. This investment should ideally allow easier access to newly diagnosed AF patients to specialist AF services for early screening of appropriateness of ablation treatment, resulting in improved availability of AF ablation to those in need. Regular review of the clinical and economic evidence supporting AF ablation treatment is required by committees of national frameworks, guidelines and policies to enable improvement in standard of care, particularly as studies with new generation catheters or first line approaches are published.

5.2 Limitations

There are several limitations that should be considered when evaluating the results and interpretation of this study. While the cost of ablation was based on state-of-the-art catheters, much of the clinical evidence evaluated ablation procedures that were performed before the availability of this technology. Therefore, the clinical benefit and cost-effectiveness may be underestimated in this study.

Clinical events data were derived from a US-based population, rather than a UK population. We selected the Noseworthy et al. study for its large, well-matched, and generalizable patient population, and reporting of endpoints modeled on the CABANA trial. Likewise, AF recurrence data were extracted from randomized trials, not limited to those conducted in the UK. We do not expect that clinical endpoints should vary dramatically by region. Regardless, there may be elements of clinical practice and patient selection in other countries, which are not directly comparable to those of the UK. Additionally, while the medical therapy arm of this analysis assumes all patients were on rhythm control drugs at baseline, some of the studies used to populate the data included a relatively small portion of patients that were on rate-control drugs only. Given there was only a small number of these patients, this is unlikely to have an impact on the study results.

Another important limitation was the modeled life-time horizon. There was no direct clinical evidence evaluating the treatment effect over a patient's lifetime, as the longest follow-up time was 12 years. To mitigate any bias in extrapolation of the data, no difference in CV adverse event rates or mortality were modeled between the two groups after the first 7 years. Also, the treatment protocol for AF recurrence limited the length of time that the treatment effect was extrapolated by directing patients through a pathway of attempting other treatments, such as starting/switching antiarrhythmic drugs or receiving a repeat ablation, and limits the duration of follow-up for many patients by eventually funneling them to the cease rhythm control health state. Also, as a function of the long-term follow-up and treatment protocol, patients in the model that experienced recurrence were are all managed the same regardless of their age when AF recurrence occurs. In clinical practice, it is possible that patients may be managed differently depending on their age and other comorbid conditions.

This model did not account for inevitable crossover from medical therapy to catheter ablation, which is common in clinical practice (i.e., 27.5% of patients crossed over from medical therapy to ablation in the CABANA study),34 but this was done to ensure a clear comparison of the ablation and medical therapy treatment strategies to assess cost-effectiveness. It is important to note that in the current environment, worsened by the coronavirus pandemic, it is not unusual to find patients deemed suitable for catheter ablation to remain on the waiting list for the procedure over a prolonged period, over three cycles (9 months) duration as per model. In this period, antiarrhythmic drug therapy may be used as a bridging measure. This period is akin to a treatment crossover despite original intentions by both patient and specialist opinion and only adds further to healthcare provider costs in addition to reduced patient quality of life.

Only one repeat ablation was modeled. In clinical practice, it is possible that patients may experience multiple repeat ablations and the cost of these procedures may vary from the index ablation; however, there is a lack of published data on the costs and utilization of multiple ablation attempts.

Finally, this model only considers direct costs to the health provider- NHS and PSS. The model does not capture out-of-pocket expenses for patients, nor does it consider burdens such as missed time from work, reduced productivity, or the burden on caregivers, particularly for those suffering a disabling CV adverse event.

AF subsets and for first line treatment of AF were not analyzed in this model due to data limitation on sub-sets such as longstanding persistent AFs, who are not as widely studied and their treatment needs differ markedly from those with paroxysmal or early to intermediate persistent AF. These groups will become the focus of future study as more data becomes available especially for those receiving first line treatment with either catheter ablation or medical therapy, where three randomized trials have recently become available.45-47