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At Issue: Publication of CABANA results prompts further debate over AF ablation
When the results of the CABANA trial of atrial fibrillation ablation compared with medical therapy were presented at the Heart Rhythm Society Annual Scientific Sessions in May 2018, reaction was swift and vociferous.
As Cardiology Today previously reported, in the intention-to-treat analysis, there was no difference between the groups in the primary endpoint of death, disabling stroke, serious bleeding or cardiac arrest after a median follow-up of 4 years, but the on-treatment and per-protocol analyses favored ablation.
Given the mixed messages from the presentation, many in the cardiology community said at the time that they would reserve judgment until the study was published in a peer-reviewed journal. That happened in March, when the main results and a quality-of-life analysis appeared in JAMA.
In the main study, no prespecified subgroups had a treatment effect from ablation large enough to be clinically significant for the primary outcome in the intention-to-treat analysis, and AF recurrence analyzed with death as a competing risk was reduced by 48% in the ablation group vs. the medical therapy group. In the quality-of-life analysis, the Atrial Fibrillation Effect on Quality of Life summary score favored the ablation group at 12 months, as did the Mayo AF-Specific Symptom Inventory frequency and severity scores.
Cardiology Today asked some members of its Editorial Board and Next Gen Innovators to discuss whether the publications offer any clarity on whether AF ablation is an appropriate treatment and, if so, who are the best candidates for it.
Jagmeet Singh, MD, DPhil, Massachusetts General Hospital and Harvard Medical School
The published findings are up-front that the intention-to-treat analysis showed that catheter ablation was not superior to conventional medical therapy. On this front, the trial could even be considered indeterminate. Notably, the patients within the ablation arm did do much better than the medical therapy arm in terms of freedom from AF recurrence and the composite endpoint. The per-protocol analysis does indicate that ablation could be considered superior to the medical therapy arm.
The CABANA patient population is reflective of our everyday patient population that undergo catheter ablation. From the quality-of-life perspective, compared with prior studies, CABANA is the largest with the longest follow-up, and shows that the ablation arm was superior to the drug therapy arm. An important finding to note here is that a substantial proportion of patients in the drug therapy arm also showed an improvement in their AF-related symptoms and quality of life. Also, the worse the baseline symptom status of the patient, the greater likelihood of benefit. The fact that there is no difference in the primary endpoint, and that quality of life improved in both arms, suggests the need for shared decision-making with the patient while deciding the appropriate treatment strategy.
There are many questions that need to be answered as to which subset of AF ablation patients derived the maximal benefit, and was there any interaction between the ablative strategy, left atrial size and other patient-specific covariates on clinical outcomes.
Albert L. Waldo, MD, PhD (Hon.), Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center
The published main findings of CABANA simply expand on what was presented last year at HRS, providing more detail, but the same theme. Perhaps the most valuable thing that resulted from the study is that ablation of AF as first-line therapy was remarkably safe. But still, we must remember that there is a reported incidence of mortality associated with AF ablation, as high as 0.42%, ie, about 4.2 in hospital deaths per 1,000 procedures in the United States.
My own opinion is that ablation is a good tool and sometimes should be the treatment of first choice. Keep in mind, however, that ablation is empiric. The only thing we understand for sure is that AF is triggered by impulses from pulmonary veins. Everyone agrees that isolation of the pulmonary vein is necessary, but a vulnerable substrate is also needed for AF to take hold. There also appears to be a connection between inflammation and AF. It’s a tough nut to crack.
The quality-of-life analysis confirms that the absence of AF is better than the presence of AF, and absence is more likely following ablation. But we must remember that recurrence of AF is common whatever the therapy.
We need a thorough understanding of the mechanism or mechanisms that sustain AF. Then, we can go after them with targeted ablation, and the expectation of a predictably high success rate.
Daniel J. Cantillon, MD, Cleveland Clinic
The CABANA quality-of-life analysis firstly demonstrates that both the drug and procedurally treated patients derived significant gains. However, catheter ablation solidly beat drug therapy head-to-head, where approximately 14% more patients enjoyed complete or near complete relief of AF symptoms at 1 year follow-up.
AF quality-of-life improvements appear to be driven by results. Catheter ablation simply outperformed drug therapy in this trial in terms of freedom from AF. In addition, drug-related side effects, adverse reactions and treatment-related inconveniences such as need for additional laboratory tests, refills and drug costs are also likely to play a role because they continue in perpetuity, whereas procedurally treated patients make perhaps greater sacrifices up front in terms of risk and recovery but are later rewarded with better outcomes.
The obvious and important implication is that we need to prioritize the most highly symptomatic patients for procedural treatment, as well as those with clinical characteristics amenable to the best possible ablation outcomes.
These findings appropriately refocus our field on AF treatment as a means to improve quality of life. It elevates the importance of dedicated research using patient-reported outcomes, such as our own AF Tracker program, while leveraging digital health technology to better connect us with our patients. – by Erik Swain
References:
Mark DB, et al. JAMA. 2019;doi:10.1001/jama.2019.0692.
Packer DL, et al. JAMA. 2019;doi:10.1001/jama.2019.0693.
Disclosures: Cantillon reports he consults or serves on a steering committee for Abbott, Boston Scientific and Stryker Sustainability. Singh reports he has financial ties with several device companies, none of which are relevant to the present study. Waldo reports no relevant financial disclosures.