Atrial fibrillation, or AFib, is the most common cardiac arrhythmia, and increases risk
of both thromboembolic stroke and heart failure.
Treatment of AFib involves heart rate control or restoration
of sinus rhythm using either medication, or cardiac catheter ablation.
Ablation intentionally damages a small part of the cardiac muscle using either radiofrequency
or cryoablation to isolate rapidly firing impulses around the pulmonary veins.
JAMA is publishing 2 reports of the CABANA trial, a randomized,
open-label clinical trial designed to compare the effects of drug therapy vs ablation
on a composite outcome of death, disabling stroke, serious bleeding,
or cardiac arrest in patients with symptomatic AFib.
Researchers randomized over 2200 patients
to receive either Catheter Ablation or Drug Therapy.
Let's review the results.
In a standard intention-to-treat analysis in which events were counted as being a result
of the treatment participants were randomized to, there was no difference in outcomes
between the 2 treatments over 4 years of follow-up.
However, the trial was complicated by a large number of crossovers: nearly 28% of the patients
in the drug therapy group underwent ablation,
while 9% of the patients randomized to ablation did not receive it.
Crossovers between trial arms tend to be due to patient characteristics rather than occurring
at random, and their effect on trial results is difficult to know,
though they tend to obscure differences in effect between groups
and result in "no difference" conclusions.
So the authors conducted secondary analyses.
In an on-treatment analysis, patients who crossed over were included in trial groups based
on the treatment they were receiving at the time.
So patients assigned to drug therapy who received ablation were counted as being
in the drug therapy group before the ablation, and in the catheter ablation group after.
Patients in the ablation group who did not receive an ablation were counted as being
in the drug therapy group for the trial duration.
The authors also conducted a per protocol analysis, where patients were included
in trial groups only if they followed the trial protocol.
So patients assigned to drug therapy who crossed over to ablation were counted as being
in the drug therapy group before the crossover but not after, and patients assigned
to ablation were counted if they underwent the procedure within a year as defined
by the trial protocol, but not if they underwent the procedure later
or crossed over to drug treatment.
Both of these analyses, which are also subject to bias, favored the ablation procedure
over medical treatment for the composite outcome.
An important secondary endpoint in the trial was recurrence of atrial fibrillation,
which was reduced by 48% in the ablation group compared with the drug therapy group.
Thus, ablation was effective for the purpose for which it was developed - to prevent AFib.
Superior prevention of AFib recurrences translated into a modest, but statistically
and clinically significantly greater improvement in quality of life
in the ablation group compared with the drug therapy group.
Improvement in quality of life with ablation was confirmed in a second smaller European trial,
also recently published in JAMA, which compared medical treatment to ablation.
What do the results imply for clinical decisions?
Given the null result for the CABANA primary endpoint in the ITT analysis,
patients and physicians should discuss the benefits and risks of the 2 approaches detailed
in these reports and decide together what makes sense for the patient.
For patients who opt for drug therapy, an ablation may be performed later
if symptoms persist, if drug therapy is not tolerated, or if quality of life is not optimal.
Two editorialists note that "For patients with symptoms, in whom quality of life is impaired
by AF, AF ablation can improve quality of life to a greater extent than drug therapy.
However, patients who choose drug therapy will also likely experience significant improvements
in quality of life and have no worse risk
for the most concerning complications of AF, stroke or death.
Thus, there is no mandate for patients currently on drug therapy
to undergo AF ablation at this time."
A few additional clinical considerations: First, ablation may be preferred
over drug therapy based on the previously published CASTLE-AF trial findings,
which reported mortality reductions in patients with AFib and heart failure.
Second, patients with a CHA2D2s-VASc score greater than 0, indicating higher risk
of thromboembolic stroke, should be anticoagulated given
that AFib may recur with either therapy.
Finally, the most recent update of the AFib clinical guideline underscores the importance
of weight loss as an effective intervention in controlling this very common arrhythmia.
Click the link in the description to read these papers and learn more.