A recent randomized trial in Czechia tested the premise that lifestyle modification and use of antiarrhythmic drugs was as effective as catheter ablation (CA) to treat atrial fibrillation (AF).
The bottom line: Ablation alone was better than the combination of the two noninvasive approaches in tandem at keeping these patients free from AF after a year.
But some electrophysiologists say the trial results should not mean clinicians should default to one approach vs the other but rather that they help validate a combination of ablation plus lifestyle modification to optimize outcomes for patients with AF.
A ‘Hybrid Approach’
The PRAGUE-25 trial randomized 212 patients with AF to CA alone or lifestyle modification plus medication to control their arrhythmias. The primary endpoint was freedom from AF at 12 months, achieved by 73% of patients in the ablation-only group and 34.6% of those who had lifestyle modification plus medication therapy. At 24 months, that outcome had shifted to 55.6% of the former and 24.7% of the latter.
“I personally think that ultimately what’s important is a hybrid approach,” Sana Al-Khatib, MD, MHS, an electrophysiologist at Duke University in Durham, North Carolina, told Medscape Medical News. “You, of course, control the patient’s risk factors and also consider them for catheter ablation because we know it’s superior for rhythm control vs medication, but for the results of the catheter ablation to be optimized, and in my view to ensure the durability of the effect of catheter ablation, I think controlling risk factors like lifestyle modification is very important.”
“The results of trial suggest to no surprise that catheter ablation is a very, very powerful treatment, far more effective than risk factor modification,” said Kenneth Ellenbogen, MD, former president of the Heart Rhythm Society and an electrophysiologist at the Pauley Heart Center, Virginia Commonwealth University, in Richmond, Virginia.
Although Ellenbogen said he considers PRAGUE-25 “an important trial, the take-home message for cardiologists should be that everyone can have risk factor modification — and catheter ablation. The patients who do both are going to do better than the patients who do one or the other,” he said.
A study comparing patients who had ablation plus risk factor modification compared with ablation alone “would’ve been interesting,” he added.
The Importance of Sinus Rhythm
The PRAGUE 25 researchers based their premise on the 2015 LEGACY trial, a study that followed patients with overweight on weight management over 5 years that found an association between sustained weight loss and a sharp reduction in AF burden and maintenance of sinus rhythm (SR).
The importance of maintaining SR received an endorsement last year with an analysis of patients in the CABANA trial (CA vs Antiarrhythmic Drug Therapy for AF). The analysis of 883 patients with AF found those in SR were 43% less likely to meet the primary endpoint — death, disabling stroke, serious bleeding, or cardiac arrest — than those who did not have SR, regardless of whether they had received ablation or were taking therapy. Patients in normal rhythm had a 41% lower risk for all-cause death.
The evidence supporting the benefit of prioritizing SR over rate control has evolved steadily over the past three decades, said Eric Prystowsky, MD, director of Cardiac Arrhythmia Service at Ascension St. Vincent Hospital in Indianapolis, and a consulting professor at Duke University Medical Center, Durham, North Carolina. Rate control became the preferred strategy after the AFFIRM trial in 2002 and found rhythm control offered no survival advantage compared with rate control, with the latter having potential advantages, such as fewer adverse drug reactions and lower risk for death.
Within a few years, more data tipped the scales in favor of rhythm control. In 2009 the CAFÉ-II study, although small (61 patients), found restoring SR in patients with AF and heart failure improved quality of life and left ventricular function better than rate control. By 2018, Prystowsky was calling SR “a bridge to the future” in patients with AF.
“The bridge to the future concept is to understand that, if I as a physician don’t do anything, you’ll be in Afib [AF] for the rest of your life and that can have debilitating consequences for the future,” Prystowsky told Medscape Medical News.
That same year, the CASTLE-AF study concluded ablation was more effective at maintaining SR and reducing the risk of worsening heart failure than medical therapy.
In a 2022 commentary in the journal Circulation, Prystowsky asked if the debate of rate vs rhythm control had been settled. Clinicians should discuss the benefits of SR with patients when AF is first diagnosed, he wrote, with rhythm control the preferred option in patients with heart failure and those aged 70 years and younger.
In an editorial last year in Circulation: Arrhythmia and Electrophysiology, Al-Khatib pointed out guidance from the American Heart Association/American College of Cardiology/Heart Rhythm Society between 2014 and 2019 recommended rhythm control in patients who had symptoms despite adequate rate control, making rhythm control subordinate to rate control.
In 2023, the three groups updated their statement to recommend early rhythm control and focusing on maintaining SR and minimizing the burden of AF burden for management of the condition. Maintaining SR “can be useful” to reduce hospitalization, stroke, death and AF progression in patients who had been diagnosed with AF in the past year, the groups stated. The tide had turned in favor of SR compared with rate control.
“In the past it was difficult to keep everyone in sinus rhythm, but we have newer methods now that are much more effective and it’s not quite the struggle,” Prystowsky said. “But it does require patience. It requires you to know a lot about antiarrhythmic drugs because ablation is not the only option. And it requires that you know what techniques are best for which patient. It’s not an easy process.”
“Atrial fibrillation,” he added, “is easy to diagnose and frankly hard to treat.”
Getting to Sinus
The first step, experts said, is convincing patients that rhythm control is essential.
“It’s important to keep this in mind when we see these patients to counsel them to make sure that they understand that unless you do something about the atrial fibrillation to try to keep them in sinus rhythm, in many patients atrial fibrillation gets worse over time,” Al-Khatib said.
Ablation isn’t for everyone with AF, Prystowsky said. “Patients in their mid-to-late 80s that are comfortable in Afib may not be appropriate,” he said. “It’s not that everybody needs it, but the discussion and consideration of sinus rhythm is appropriate for every patient.”
Lifestyle modification is “very hard, though,” he said. “Without an organized program for weight loss, you just can’t get people to take off 10% of their body weight and keep it off.”
The widening availability of GLP-1 agonists for weight loss could drastically alter how cardiologists and electrophysiologists approach AF in patients who are obese and overweight, Prystowsky said. “It’s not just about losing weight. It might affect the metabolic activity of the pericardial fat and reduce Afib,” he said.
One combined approach could involve CA with antiarrhythmic medication afterward, Prystowsky said. “It’s not uncommon to do an ablation and get three quarters of the job done, and the patient is still having episodes,” he said. “Then you add a drug like dofetilide, and they have nothing. They can go for years feeling great or not need a second ablation.”
But, Ellenbogen said, “very, very, very few” patients would not be candidates for ablation.
“Antiarrhythmic drugs alone are fine, but they’re only a short-term solution,” he said. “In most people who take antiarrhythmic drugs, over time there’s progression of disease. Typically, in 2 years 50% who take antiarrhythmic drugs are back in Afib.”
When discussing AF with patients, clinicians should focus on the severity and progression of symptoms, not the mere presence of AF, Al-Khatib said. “If the patient starts with rare episodes of atrial fibrillation, I don’t think anyone would do a procedure, but you have to keep an eye on the progression of the Afib,” Al-Khatib said. “As it gets more frequent and the episodes start lasting longer, then it is important to intervene with rhythm controlling strategies earlier.”
In the end, experts said, the best strategy to achieve SR is the one that works.
“The punchline is that for maintenance of sinus rhythm, catheter ablation is the most effective method and more effective than risk factor modification,” Ellenbogen said. “But it’s a false narrative here. We want all our patients to do both, and both together is very, very profoundly effective.”
Ellenbogen disclosed honorarium from Medtronic. Al-Khatib and Prystowsky reported no relevant financial relationships.
Richard Mark Kirkner is a medical journalist based in Philadelphia.