Long-Awaited CABANA Publication Arrives, With Accompanying Quality-of-Life Study
The trial missed its primary clinical endpoint but showed that catheter ablation was associated with enhanced improvements in quality of life.
When it was presented last May at the Heart Rhythm Society (HRS) 2018 Scientific Sessions, the CABANA trial did not provide the results electrophysiologists wanted to see—it failed to show a significant reduction in death, disabling stroke, serious bleeding, or cardiac arrest, the primary endpoint, with catheter ablation versus medical therapy in patients with symptomatic A-fib.
But many observers pointed to the fact that more than a quarter of patients in the medical therapy arm ultimately underwent ablation and about 9% of those in the ablation arm did not undergo the procedure, muddying the results. In a “treatment received” analysis accounting for that, ablation showed an advantage over conservative management.
Now, in what is sure to spark another round of discussions about what can be gleaned from CABANA, the main results and a quality-of-life assessment—which was presented at the European Society of Cardiology Congress last year—have finally been published, online ahead of print in JAMA.
The top-line results are as reported at HRS, with no difference through a median follow-up of about 4 years in the rate of primary endpoint—8.0% with ablation and 9.2% with medical therapy (HR 0.86; 95% CI 0.65-1.15). The findings were consistent across subgroups.
In terms of secondary endpoints—which “may be reasonably viewed as more provisional or exploratory,” according investigators led by Douglas Packer, MD (Mayo Clinic, Rochester, MN)—there was no difference in all-cause mortality (5.2% vs 6.1%; HR 0.85; 95% CI 0.60-1.21) but a significant advantage for ablation for a composite of mortality or CV hospitalization (51.7% vs 58.1%; HR 0.83; 95% CI 0.74-0.93) and A-fib recurrence (49.9% vs 69.5%; HR 0.52; 95% CI 0.45-0.60).
The researchers say that the primary intention-to-treat analysis is inconclusive because of a lack of statistical precision and conclude that even though the primary endpoint was missed, “the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial.”
They note, too, that “for most patients with atrial fibrillation, the primary reason to consider catheter ablation is to mitigate the disruption that [the condition] creates in their daily lives and consequent reductions in quality of life.”
Addressing that point, a separate paper, with lead author Daniel Mark, MD (Duke Clinical Research Institute, Durham, NC), contained the secondary quality-of-life results from the trial, and these were more favorable for catheter ablation.
Quality of life was assessed using two tools: the Atrial Fibrillation Effect on Quality of Life (AFEQT) summary score and the Mayo AF-Specific Symptom Inventory (MAFSI) frequency and severity scores. At 12 months, both measures indicated that quality of life improved to a greater extent with catheter ablation than with medical therapy, with between-group differences exceeding thresholds deemed to be clinically important.
“These findings can help guide decisions regarding management of atrial fibrillation,” Mark et al say.
Essential Data to Optimize A-fib Care
In an accompanying editorial, Christine Albert, MD, and Deepak Bhatt, MD (both Brigham and Women’s Hospital, Boston, MA), point out that treatment of A-fib has two goals, to reduce related morbidity and mortality and to improve quality of life.
Though the primary composite endpoint of the CABANA trial was not reduced, they note that A-fib recurrence and the composite of death or CV hospitalization were significantly lowered with ablation.
“In many heart failure trials, a reduction in cardiovascular hospitalizations would be viewed as a successful result,” they say.
CABANA also showed that quality of life was improved to a greater degree with ablation versus medical therapy, a finding that was bolstered by a smaller randomized trial—CAPTAF, with 155 patients—that was also published online in JAMA. “These two separate quality-of-life trials with consistent findings make this a robust observation,” Albert and Bhatt say.
They introduce some cautionary notes, however. For one, the open-label design of the trial introduces potential bias. Also, the effects of protocol adherence and crossover on the how the trial came out is unknown.
Nevertheless, Albert and Bhatt say, “While it is true that the CABANA trial did not meet its primary endpoint in the intention-to-treat analyses (and this is the most rigorous way to evaluate trial results), this study provides important, clinically relevant insights regarding current treatment options for atrial fibrillation management.”
The trial establishes the safety of catheter ablation in skilled hands and shows that ablation provides an extra boost in quality of life, they write, adding, however, that “there is no mandate” for these types of patients to undergo ablation because medical therapy also results in better quality of life without worsening hard outcomes.
It’s also possible, Albert and Bhatt point out, that ablation has more modest beneficial effects on hard clinical outcomes than could be detected in CABANA, in which event rates were lower than expected, and that certain subgroups of patients will derive greater benefits with ablation.
“Where does this leave the patient with atrial fibrillation? Shared decision-making between the cardiologist and the patient is the best answer and is critical in determining treatment. The CABANA trial provides a wealth of additional data regarding the comparative benefits and risks of catheter ablation versus drug therapy to inform this process,” Albert and Bhatt write.
“This approach may be well positioned to occur in comprehensive atrial fibrillation management centers that offer the full range of anticoagulation options, antiarrhythmic drug therapy, and percutaneous and surgical procedures, coupled with lifestyle modification, such as weight loss, that may further augment the success of ablation, medical therapies, or both,” they conclude. “Thus, the CABANA trial provides essential information to optimize the care of patients with atrial fibrillation in a very patient-centric way.”
It remains to be seen what impact the publication of the CABANA results will have on practice, but the trial is sure to be a hot topic of discussion at the American College of Cardiology 2019 Scientific Session and the European Heart Rhythm Association Congress 2019, which both kick off this weekend.
Packer DL, Mark DB, Robb RA, et al. Effect of catheter ablation vs antiarrhythmic drug therapy on mortality, stroke, bleeding, and cardiac arrest among patients with atrial fibrillation: the CABANA randomized clinical trial. JAMA. 2019;Epub ahead of print.
Mark DB, Anstrom KJ, Sheng S, et al. Effect of catheter ablation vs medical therapy on quality of life among patients with atrial fibrillation: the CABANA randomized clinical trial. JAMA. 2019;Epub ahead of print.
Blomström-Lundqvist C, Gizurarson S, Schwieler J, et al. Effect of catheter ablation vs antiarrhythmic medication on quality of life in patients with atrial fibrillation: the CAPTAF randomized clinical trial. JAMA. 2019;Epub ahead of print.
Albert CM, Bhatt DL. Catheter ablation for atrial fibrillation: lessons learned from CABANA. JAMA. 2019;Epub ahead of print.
- CABANA was funded by the US National Institutes of Health (NIH), St. Jude Medical, Biosense Webster, Medtronic, and Boston Scientific.
- Packer reports receiving grants from the NIH/National Heart, Lung, and Blood Institute, St. Jude Medical, Biosense Webster, Medtronic, and Boston Scientific during the study and from Abbott, Biosense Webster, Boston Scientific, CardioFocus, Medtronic, St. Jude Medical, CardioInsight, the NIH, Siemens, Thermedical, Endosense, the Robertson Foundation, and Hansen Medical unrelated to the study. He also reports serving on the advisory board without compensation for Abbott, Biosense Webster, Boston Scientific, CardioFocus, Medtronic, St. Jude Medical, Spectrum Dynamics, Siemens, Thermedical, Johnson & Johnson, and SigNum Preemptive Healthcare; speaking with honoraria from Biotronik and MediaSphere Medical; and receiving royalties from Wiley & Sons, Oxford, and St. Jude Medical. Packer and the Mayo Clinic jointly have equity in a privately held company, External Beam Ablation Medical Devices. Packer also has mapping technologies with royalties paid.
- Mark reports receiving grants from the NIH and the Mayo Clinic during the study. He also reports receiving grants from Merck, Oxygen Therapeutics, Bristol-Myers Squibb, AstraZeneca, the University of Calgary, Eli Lilly, AGA Medical, St. Jude Medical, and Tufts University and personal fees from CeleCor and Novo Nordisk unrelated to the study.
- CAPTAF was funded by unrestricted grants from the Swedish Heart-Lung Foundation, the Swedish Research Council, and Medtronic AB.
- Blomström-Lundqvist reports receiving grants from Medtronic during the study and personal fees from Bayer, Sanofi, Boston Scientific, and Merck Sharp & Dohme unrelated to the study.
- Albert reports serving on the advisory board of Roche Diagnostics, as a consultant for Myocardia and Sanofi US Services, and as a data and safety monitoring board member of the Apple Watch Study; and receiving research funding from the National Heart, Lung, and Blood Institute, St.
- Jude Medical, Abbott, and Roche Diagnostics. Albert is currently vice president of the Heart Rhythm Society.
- Bhatt reports receiving research funding or unfunded research support from Abbott, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, Regeneron, Roche, Sanofi, Synaptic, The Medicines Company, FlowCo, Merck, Novo Nordisk, PLx Pharma, and Takeda; being a site co-investigator for Biotronik, Boston Scientific, St. Jude Medical, and Svelte; being a trustee for the American College of Cardiology; serving as an advisory board member, director, or chair for Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; the Boston VA Research Institute, the Society of Cardiovascular Patient Care, and TobeSoft; serving on the American Heart Association Quality Oversight Committee; serving on a range of data safety monitoring committees; receiving honoraria for editorial or committee activities for a range of publications and organizations; and receiving royalties from Elsevier.