CABANA Published: Mixed Results, Helpful Insights

March 16, 2019

The CABANA trial showed no significant difference for its clinical primary endpoint between the strategies of ablation or rate- or rhythm-control meds alone in patients with atrial fibrillation (AF). The null outcome, however, may still help to enlighten current clinical practice, say observers on the randomized trial's formal publication March 15 in JAMA.

Ablation, compared to medical therapy alone, significantly improved quality of life and some important secondary clinical endpoints, including time to AF recurrence, in the trial's patients with paroxysmal or persistent AF.

But medically treated patients fared well for a number of outcomes, too, in addition to matching the ablation group for the primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest in the primary intention-to-treat (ITT) analysis over the follow-up, which  averaged 4 years. The risk was 14% lower in the ablation group, but the difference was nonsignificant (P = .30).

Those in the medical-therapy arm also showed significantly improved quality of life and symptom scores, although not by as much as in patients assigned to ablation.

The primary CABANA report and its separately published quality-of-life analysis appeared March 15 in the journal, with lead authors Douglas L. Packer, MD, Mayo Clinic, Rochester, Minnesota, and Daniel B. Mark, MD, MPH, Duke Clinical Research Institute, Durham, North Carolina, respectively.

The primary findings had been presented in preliminary form at the May 2018 Heart Rhythm Society sessions and covered at the time by theheart.org | Medscape Cardiology, with essentially the same findings.

"The CABANA trial provides a wealth of additional data regarding the comparative benefits and risks of catheter ablation vs drug therapy" to inform the shared decision-making process with patients with AF,  notes an accompanying editorial written by Christine M. Albert, MD, MPH, and Deepak L. Bhatt, MD, MPH, both from Brigham and Women's Hospital, Boston, Massachusetts.

"The CABANA trial provides essential information to optimize the care of patients with AF in a very patient-centric way."

Alternative Analyses                                      

The main CABANA report also features several prespecified sensitivity analyses, including one comparing the patients on the basis of "treatment received" and, separately, treatment "per protocol."

Both try to reconcile analytic biases from, for example, patients who don't receive their assigned treatment or cross over from one arm to the other in the unblinded trial. About 91% of patients assigned to the ablation arm actually underwent the procedure, and of those assigned to medical management, 27.5% eventually underwent catheter ablation.

In the treatment-received analysis, ablation showed a significant advantage over meds only, a 33% drop in risk for the primary endpoint (P = .006). The results were similar in the per-protocol analysis.

"The on-treatment analysis does give you insight, I think, into the data. I certainly would put more weight on the intention-to-treat analysis, but I wouldn't completely dismiss the on-treatment analysis," Sana M. Al-Khatib, MD, MHS, Duke University Medical Center, told theheart.org | Medscape Cardiology

And the ITT analysis, if not the primary endpoint result itself, does provide some encouragement about the value of catheter ablation for AF, which is usually aimed at symptoms and improving quality of life more than at preventing catastrophic outcomes.

Some of the secondary endpoints, such as death or cardiovascular hospitalization, as well as AF recurrence, significantly favored the ablation arm, as did most of the formally assessed quality-of-life endpoints, noted Al-Khatib, who is not a CABANA coauthor.

"Most of us do this procedure, or refer patients for ablation procedures, to help them feel better," she said. "A lot of patients have debilitating symptoms, so being able to help them feel better, be more functional, have a better quality of life, is a really important endpoint for a lot of patients."

Catheter ablation can play a big role in AF management, "but perhaps it's not a treatment for everyone," Al-Khatib said. CABANA and its quality-of-life analysis "can certainly help inform discussions with the patients."

Intention to Treat

The international CABANA trial randomly assigned 1108 patients with symptomatic AF to undergo catheter ablation for pulmonary vein isolation and 1096 to receive standard rhythm- and/or rate-control medications; those in the ablation group could also be on such medical therapy.

The arrhythmia had been persistent in about 57% of patients and paroxysmal in the rest; about 37% of the population were women.

The hazard ratio (HR) for the primary endpoint was 0.86 (95% CI, 0.65 - 1.15; P = .30) for ablation vs meds over a median of 48.5 months in the ITT analysis. It was 0.85 (95% CI, 0.60 - 1.21; P = .38) for all-cause mortality by itself. Nor was the difference significant for any other components of the primary endpoint.

On the other hand, the HR for the secondary endpoint of death or cardiovascular hospitalization was 0.83 (95% CI, 0.74 - 0.93; P = .001) and for AF recurrence after the 3-month postablation blanking period was 0.52 (95% CI, 0.45 - 0.60; P < .001).

Both groups showed significant improvements in Atrial Fibrillation Effect on Quality of Life (AFEQT) summary scores and the separate Mayo AF-Specific Symptom Inventory (MAFSI) frequency and severity scores, which were assessed throughout the follow-up. Scores for the two groups were not significantly different at baseline.

But improvements in the ablation group were significantly greater than those in the medical-therapy group on all three tests at both 12 months and across the entire follow-up (P < .001).

Table. CABANA: Mean Adjusted Differences (Ablation Group vs Medical Group) Between Quality of Life and Symptom Scores by ITT Over Time

Interval AFEQT Summary Score MAFSI Frequency Score MAFSI Severity Score
12 mo 5.3 –1.7 –1.5
By end of follow-up 3.4 –1.4 –1.1
All differences P < .001.

 

Rates of adverse events in the trial, which required operators to have at least 100 such procedures under their belt, were similar to what has been reported for AF ablation in the literature, the authors note.

In the ablation group, the rate of hematoma was 2.3%, pseudoaneurysm 1.1%, severe pericardial chest pain 1.1%, cardiac tamponade from perforation 0.8%, and esophageal lesions 0.5%.

Complications in the medical therapy group included thyroid abnormalities in 1.6%, major ventricular proarrhythmia in 0.8% (and atrial proarrhythmia in 0.1%), allergic reaction in 0.6%, and hypotension in 0.3%.

"That actually was very reassuring to me," Al-Khatib said about the low complication rates in the ablation group.

"Granted, maybe the sites that participated in the trial, one could argue, are better at performing these procedure than the average site," she said. But given the 126 participating sites in 10 countries, she added, there was probably a range of experience and skills.

CABANA received support from St Jude Medical, Biosense Webster, Medtronic, and Boston Scientific. Packer had no relevant conflicts. Mark discloses receiving grants from Merck, Oxygen Therapeutics, Bristol-Myers Squibb, AstraZeneca, Eli Lilly & Company, AGA Medical, and St Jude Medical; and personal fees from CeleCor and Novo Nordisk. Disclosures for the other authors are in the reports. Albert discloses serving on an advisory board for Roche Diagnostics and as a consultant for Myocardia and Sanofi; serving on the Apple Heart Study data and safety monitoring board (DSMB); and receiving research funding from St Jude Medical, Abbott, and Roche Diagnostics. Bhatt discloses serving on advisory board of Cardax, Medscape Cardiology, PhaseBio, and Regado Biosciences; the board of directors of TobeSoft; the DSMB of the St Jude Medical PORTICO trial funded by St Jude Medical, the ExCEED trial funded by Edwards Lifesciences, and the ENVISAGE trial funded by Daiichi Sankyo; receiving honoraria for committee work on trials funded by Boehringer Ingelheim and Bayer and for serving on a WebMD steering committee; receiving research funding from Abbott, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Idorsia, Ironwood, Ischemix, Eli Lilly, Medtronic, PhaseBio, Pfizer, Regeneron, Roche, Sanofi Aventis, Synaptic, and The Medicines Company; serving as site coinvestigator for Biotronik, Boston Scientific, St Jude Medical, and Svelte; and having uncompensated research collaborations with FlowCo, Fractyl, Merck, Novo Nordisk, PLx Pharma, and Takeda. Al-Khatib reported no conflicts.

JAMA. Published online March 15, 2019. Primary report, Data supplement, Quality-of-life report, Editorial

Follow Steve Stiles on Twitter: @SteveStiles2. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....

Recommendations