Key Points:
- Obesity increases the risk of atrial fibrillation (AF) by 19–29% for every 5-unit increase in BMI. While catheter ablation has been more effective than antiarrhythmic drugs (AADs), the impact of lifestyle changes combined with AADs had not been thoroughly tested against catheter ablation.
- The PRAGUE-25 trial compared catheter ablation to lifestyle modification, including weight loss, combined with AADs in obese patients with AF.
- At 12 months, freedom from AF was significantly higher with catheter ablation (73.0%) than with lifestyle changes and AADs (34.6%).
- Despite improvements in metabolic health and physical fitness, lifestyle changes with AADs were not as effective as ablation in maintaining normal heart rhythm.
In a Featured Clinical Research session at ACC.2025, Dr. Pavel Osmancik (Charles University, Prague) presented the PRAGUE-25 trial results. The study investigated whether risk factor modification (RFM) with AADs could achieve non-inferior rhythm control compared to catheter ablation in obese patients with AF.
Obesity is a well-established risk factor for AF, with prior studies (CABANA, EARLY-AF, ADVENT) showing a high prevalence of obesity among patients undergoing ablation (median BMI 28.5–30 kg/m²). The LEGACY study demonstrated that weight loss alone significantly improved AF outcomes, suggesting a potential role for lifestyle interventions. While previous studies consistently found catheter ablation superior to antiarrhythmic drugs (AADs) for controlling AF, the combination of lifestyle changes and AADs had not been rigorously compared to ablation.
PRAGUE-25 was a multicenter, investigator-initiated, non-inferiority randomized controlled trial (RCT) funded by the Czech Ministry of Health. It enrolled symptomatic AF patients with a BMI of 30–40 kg/m². Exclusion criteria included AF-induced cardiomyopathy, LVEF < 40%, BMI > 40, contraindications to AADs, age > 75 years, and physical limitations affecting activity.
These patients were randomized to catheter ablation or RFM + AADs. In the catheter ablation arm, most patients underwent pulmonary vein isolation (PVI) or PVI + additional ablation for non-paroxysmal AF, using either pulse field or RF energy, within six weeks of randomization. All patients underwent a baseline exam within four weeks of randomization, including cardiopulmonary exercise testing (peak VO₂ max), 7-day ECG Holter recording, echocardiography, blood biomarkers (HbA1c, lipids, NT-proBNP, CRP), and quality-of-life assessment (AFEQT questionnaire).
The primary endpoint was AF freedom at 12 months, defined as the absence of atrial tachyarrhythmia (AF, atrial flutter, atrial tachycardia) lasting > 30 seconds post-blanking period. Rhythm monitoring was performed via 7-day Holter recording every three months in the first year and every six months thereafter. Secondary outcomes included AF burden, peak VO₂ uptake, AFEQT score, and metabolic parameters (HbA1c, lipids, NT-proBNP, CRP).
Between May 2021 and November 2023, 203 patients (68% male, BMI 35, 56% with paroxysmal AF) were enrolled. In the RFM + AADs group, the average weight loss at 12 months was 6.3 kg, and 66% remained on AADs at one year.
At 12 months, AF freedom was achieved in 73.0% (95% CI 64.3–81.7%) of the catheter ablation group and 34.6% (95% CI 25.3–43.9%) of the RFM + AADs group (p for non-inferiority = 0.99, p for superiority < 0.001). There were no significant differences in secondary outcomes, including HbA1c, triglycerides, cholesterol, VO₂ max, AF burden, and AFEQT scores. However, significant improvements in peak oxygen uptake (+0.13 ± 2.94 vs. +1.11 ± 3.88 mL/min/kg, p=0.02) and a decrease in HbA1c (-1.4 ± 4.8 vs. +2.5 ± 10.5 mmol/L, p=0.04) were observed only in the RFM + AADs arm.
Despite these metabolic and functional benefits, Dr. Pavel Osmancick, the lead study investigator, concluded that a treatment strategy based on RFM with AADs was inferior to catheter ablation for maintaining sinus rhythm in overweight and obese AF patients.