PRAGUE-25: Ablation Improves Rhythm Control, but Don’t Discount Lifestyle Changes

When it comes to preventing recurrences of atrial tachyarrhythmias in patients with atrial fibrillation (AF) and obesity, catheter ablation tops a combination of lifestyle modifications and antiarrhythmic drugs, the PRAGUE-25 trial shows.

However, having patients focus on cutting calories, exercising more, and consuming less alcohol, in conjunction with medical therapy, provided greater reductions in body weight and HbA1c than did ablation, highlighting a complementary role for these interventions.

Pavel Osmancik, MD, PhD (Charles University Prague and University Hospital Kralovske Vinohrady, Prague, Czech Republic), and colleagues report the findings, which were initially presented earlier this year at the American College of Cardiology 2025 Scientific Session, in the July 8, 2025, issue of JACC.

“The referral to catheter ablation in this population should not be delayed until the patient loses weight,” the researchers write. “Nonetheless, patients with obesity should not be discouraged from losing weight, because several other significant benefits are associated with weight reduction.”

Obesity is one of the strongest risk factors for AF, and prior observational research has indicated that when people lose weight and exercise more, there is a reduction in AF.

Speaking with TCTMD, Wilber Su, MD (Banner – University Medicine Heart Institute, Phoenix, AZ), noted that treatment for AF involves a mix of medication, lifestyle modification, and catheter ablation, adding that this trial’s results will not change how he practices. “You really should be doing all of it,” he advised.

There is good evidence to support catheter ablation, which has improved over the decades and now comes with a low risk of complications, Su said. But “nobody should be forgetting” about modifying other risk factors and taking steps, for instance, to get hypertension under control and address sleep apnea, he added. “These are all important things to do to try to be free from A-fib over the long term.”

The PRAGUE-25 Trial

PRAGUE-25 was designed to evaluate how an approach combining antiarrhythmic drug therapy and lifestyle modification compared with up-front catheter ablation for the prevention of arrhythmia recurrences in patients with AF.

The trial, conducted at five Czech centers, included 203 patients (mean age 60 years; 31.5% women) who had symptomatic AF and a body mass index of 30 to 40 kg/m² (mean 34.9 kg/m²). Most patients (56%) had paroxysmal AF, 39% persistent, and 5% long-standing persistent.

Among patients randomized to ablation, roughly half were treated with a radiofrequency catheter and the other half with a pulsed-field ablation system. All underwent pulmonary vein isolation and, of those with nonparoxysmal AF, 35.4% received additional lesions.

The approach for patients receiving lifestyle medication plus antiarrhythmic drug therapy was managed by teams of dietary specialists and physiotherapists. Patients were instructed to reduce calorie intake, decrease alcohol consumption, and follow individual exercise programs that were based on the results of a baseline cardiopulmonary exercise test. Choice of antiarrhythmic drugs was made according to local practices.

During follow-up, which lasted a mean of 23.5 months, patients underwent 7-day electrocardiographic Holter monitoring every 3 months for the first year and then every 6 months after that.

The primary endpoint was freedom from any atrial tachyarrhythmia lasting more than 30 seconds through 1 year (excluding an initial 3-month blanking period). This was achieved in 73.0% of patients who underwent ablation and 34.6% of those managed with lifestyle changes and medical therapy. The latter approach failed to meet criteria for noninferiority (P = 0.999), with ablation proving to be superior (P < 0.001).

On a questionnaire, most patients in the lifestyle/medication group reported that they decreased alcohol consumption (64%), increased their physical activity (77%), and used a mobile app to monitor their activity levels and communicate with dietary specialists (66%). Another 16.5% said they were treated for obstructive sleep apnea.

These efforts were associated with a greater reduction in body weight compared with ablation (mean 6.4 vs 0.4 kg; P < 0.001), as well as a larger drop in HbA1c. Though peak oxygen uptake increased to a greater extent, the difference was not statistically significant. Both groups saw similar declines in AF burden and NT-proBNP levels as well as similar improvements in quality of life, which was assessed with the Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaire.

Though the primary endpoint favored ablation, Osmancik et al say the positive metabolic changes seen in the other group “should not be underestimated.”

“Given the strong association between these positive metabolic changes and enhanced cardiovascular outcomes, the reduced effectiveness of the [lifestyle modification/medication] strategy relative to AF freedom should not dissuade obese patients from pursuing weight loss and lifestyle modification,” the authors stress.

They point out that the goal of 10% weight loss was not achieved with that strategy and that arrhythmia outcomes likely would have been better if patients had shed more pounds. Of note, only 14.6% of patients in that group used a glucagon-like peptide-1 (GLP-1) receptor agonist for a brief period of time (mean 6 months).

The Importance of Lifestyle Modification

In an accompanying editorial, Ratika Parkash, MD (Queen Elizabeth II Health Sciences Center, Halifax, Canada), and Jonathan Piccini, MD (Duke Clinical Research Institute, Durham, NC), say the PRAGUE-25 results lead to more questions than answers.

“In a population with significant cardiometabolic disease, such as the one in the present study, the most relevant clinical outcome is unlikely to be time to recurrent atrial arrhythmia of ≥ 30 seconds, but rather a composite measure of AF burden, improvement in cardiometabolic profile, and cardiovascular events,” they write.

Because there were positive effects on body weight, HbA1c, and cardiopulmonary fitness, along with no difference in AF burden, “one could argue that the lifestyle modification-antiarrhythmic drug [approach] may be noninferior to catheter ablation alone,” Parkash and Piccini said. “There is no question that catheter ablation is superior to antiarrhythmic drug therapy for the prevention of recurrent atrial arrhythmia, as demonstrated unequivocally in this trial, but the effect of lifestyle modification and its benefits cannot be minimized.”

Su noted that results of different interventions may vary depending on the stage of AF. Patients with persistent AF, for instance, may be too far advanced to be managed effectively with lifestyle modification and antiarrhythmic medications alone.

Thus, it’s not surprising that in this trial, which included a high proportion of patients with persistent or long-standing persistent disease, ablation came out on top for rhythm control, he said.

Still, treatment decisions come down to what the patient prefers, with perhaps a greater emphasis on ablation in those with persistent disease and a stronger focus on modifiable risk factors in those with early-onset AF.

Conditions like sleep apnea, obesity, and high blood pressure “are all things that we can modify early on to prevent the rapid progression of A-fib, but then when it’s too far gone, you have to resort to ablation,” Su said. But without lifestyle modification and treatment of risk factors over the long term, he added, there will be recurrences after catheter ablation.

“Ablation alone is not going to fix it. It’s an intervention to modify the existing problem at one point in time only,” Su said. “Lifestyle modification is actually to reduce the wear and tear over the long term. So to me, it’s not a comparison of what to do at this moment, it’s really that all these are important.”