Author + information
- aLahey Hospital & Medical Center, Burlington, Massachusetts
- bBaim Institute for Clinical Research, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Matthew R. Reynolds, Lahey Hospital & Medical Center, 41 Mall Road, Burlington, Massachusetts 01805.
Drawing from early mechanistic insights gained from research conducted in the 1970s and 1980s (1) as well as the development of subendocardial resection surgery (2), catheter-based ablation for recurrent ventricular tachycardia (VT) associated with prior myocardial infarction was first reported in the late 1980s (3,4). Catheter ablation gathered momentum as a therapy for postinfarction VT around the turn of the century, partly because of the development of improved ablation catheters, 3-dimensional mapping systems, and strategies for targeting scar-related arrhythmia substrates during sinus rhythm, permitting the treatment of faster, “unmappable” rhythms (5–7).
Decades later, catheter ablation has an established role in the management of recurrent postinfarction VT, yet our knowledge about the effectiveness of VT ablation derives mainly from observational studies and only a few randomized clinical trials (8,9). As a result, the field has suffered until very recently from a lack of high-level evidence regarding the relative effectiveness of VT ablation compared with antiarrhythmic drugs, particularly for important secondary endpoints such as quality of life and cost-effectiveness.
In the current issue of JACC: Clinical Electrophysiology, the VANISH (Ventricular Tachycardia Ablation versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease) trial investigators begin to fill in what has been something of a void in the literature, publishing the first trial-based cost-effectiveness analysis comparing VT ablation with antiarrhythmic drugs in patients with post-infarction VT (10).
The authors used detailed quality of life and resource utilization data collected during the trial to estimate cost-effectiveness over a 3-year time horizon from a Canadian health system perspective. The mean follow-up duration was just >2 years, so this time horizon required some extrapolation of the observed data, but less than is often required in cost-effectiveness research.
They report that, for the trial population as a whole, VT ablation slightly improved quality adjusted life years (QALYs) by about 0.14, and increased costs by about $4,800 per patient, resulting in an incremental cost-effectiveness ratio of $34,057 per QALY gained. These results for the full trial population came with considerable uncertainty, with a wide credible interval (ranging from −0.20 to 0.46) for incremental QALYs and a finding that 43% of bootstrap replications resulted in an incremental cost-effectiveness ratio >$50,000 per QALY gained, a threshold still considered to indicate “high value” by U.S. professional societies (11).
As with the primary trial outcomes (12), the health economic results were stratified by whether or not patients were treated with amiodarone at baseline. Among patients not taking amiodarone at baseline, there was no apparent clinical advantage of ablation over drug escalation, and incremental costs with ablation versus drugs were larger at about $14,000 per patient. This result suggests that VT ablation provides very poor value in health economic terms if patients have not yet tried amiodarone. In contrast, for patients already taking amiodarone at baseline (almost two-thirds of the cohort), ablation yielded 0.22 more QALYs (again, over 3 years) than drugs, and costs were marginally lower, leading to a result of economic dominance (ablation more effective and less costly).
The results of this analysis are credible and entirely consistent with the trial’s main clinical results. The cost-effectiveness results appear to be driven by 3 primary factors: 1) ablation was considerably more expensive than generic drugs; 2) ablation was much more effective than drug escalation in patients already taking amiodarone (hazard ratio: 0.55 for the primary endpoint of death, VT storm or appropriate implantable cardioverter-defibrillator shock) (12); and 3) failure of drug therapy leading to crossover ablation was much more common than redo ablation in patients already taking amiodarone (but not in patients taking sotalol). The latter findings are detailed in the article’s important Online Appendix.
This novel paper has several important strengths, including the underlying randomized study design, detailed prospective data collection with careful attention to resource utilization, and the reliance to a good extent on observed data rather than extrapolation and modeling. These strengths make the work much more robust than anything previously published on the topic (13). Although many health economic experts believe that health economic analyses should generally adopt a lifetime perspective, because there were no differences in survival between groups in the VANISH trial, the shorter time horizon was defensible and a longer time horizon would have been unlikely to lead to fundamentally different conclusions.
Of course, all studies have limitations, and this one is no exception. Although unique, the VANISH trial was not exceptionally large (259 enrolled), and this reduces the level of certainty within subgroups. Quality of life in VANISH was assessed only using the EQ-5D scale, which has good acceptance in health economics research, but is a brief and generic measurement tool. Moreover, there was >40% missing data on the EQ-5D scores after the first year of follow-up. In addition, the VANISH trial was conducted primarily in Canadian centers, and the current analysis accordingly adopted a Canadian health care system perspective; therefore, the results may not readily translate to the United States or other country contexts.
U.S. professional societies recently issued evidence-based consensus guidelines on the management of ventricular arrhythmias (14). In that document, VT ablation was endorsed as a Class I (Level of Evidence: B) intervention for patients “with prior myocardial infarction and recurrent episodes of symptomatic sustained VT, or who present with VT or ventricular fibrillation storm and have failed or are intolerant of amiodarone… or other antiarrhythmic medications.” Certainly, the desire to avoid long-term use of amiodarone is understandable at a clinical level, particularly in younger patients, because of its well-known potential for side effects and toxicity. In the VANISH trial, treatment-attributed adverse events were more than twice as common with escalated drug therapy than ablation. It therefore seems appropriate to grant clinicians and patients some latitude in choosing between VT ablation and antiarrhythmic drugs. Nonetheless, the current analysis suggests that VT ablation is a very low-value undertaking in patients who have not previously tried amiodarone, and that, from a health economic perspective, VT ablation should be the exception rather than the rule in this circumstance.
The VANISH trial has helped the field of VT ablation take a major step forward, not just in understanding the clinical effectiveness of ablation compared with drugs, but also in terms of defining important secondary endpoints such as cost effectiveness. Important as these considerations are, the results of the VANISH trial remain sobering from a clinical perspective, with nearly 60% of ablation patients reaching the composite primary outcome, and nearly 40% receiving implantable cardioverter-defibrillator shocks, over a mean of 28 months of follow-up. In its Online Appendix, the current paper further documents that quality of life, as measured by the EQ-5D, did not improve from baseline in any group. Rather, average EQ-5D scores gradually but steadily declined regardless of how VT was treated. Clearly, much work lies ahead to improve the outcomes of these patients.
↵∗ Editorials published in JACC: Clinical Electrophysiology reflect the views of the authors and do not necessarily represent the views of JACC: Clinical Electrophysiology or the American College of Cardiology.
Dr. Reynolds serves as a consultant to Medtronic and St. Jude Medical (now part of Abbott).
The author attests he is in compliance with human studies committees and animal welfare regulations of the author’s institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- 2018 American College of Cardiology Foundation
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