Beyond Rhythm Control

Austin

Alright, welcome back to the Hollie.AI Journal Club. I’m Austin, and as always, I’m joined by the ever-insightful Hollie. Today, we’re diving into the PRAGUE-25 trial, which, I’ll be honest, has been rattling around my head since I first read it. Hollie, this one’s a bit of a curveball, isn’t it?

Hollie

It really is, Austin. The trial set out to answer a big question: for obese patients with atrial fibrillation, is lifestyle modification—so, weight loss and exercise—plus antiarrhythmic drugs, as good as just going straight to catheter ablation? And, well, the numbers were pretty stark. Ablation came out on top for rhythm control: 73% of patients were free from AF at 12 months, compared to just 34.6% in the lifestyle plus drugs group. That’s not even close to non-inferiority.

Austin

Yeah, and I think a lot of us expected the lifestyle arm to do better, especially given all those observational studies. But, you know, when you randomise people, you get a different crowd—maybe less motivated, or just more representative of real-world clinics. And, honestly, the antiarrhythmic drugs they used—mostly propafenone and flecainide—aren’t exactly powerhouses in obese patients. They’re less effective, and that probably stacked the deck against the lifestyle group from the start.

Hollie

Exactly. And it’s worth noting, they only managed about 6% weight loss on average, not the 10% that’s been shown to really move the needle in previous studies like LEGACY. So, the lifestyle group was fighting an uphill battle. But, Austin, you’ve actually tried to bring some of this digital rhythm tracking into Jersey clinics, haven’t you?

Austin

Yeah, I have. We started using digital rhythm trackers—just simple wearables, nothing fancy. It’s amazing how much more you pick up when patients can log symptoms and get real-time feedback. It changes the whole management conversation. You see, in PRAGUE-25, they used seven-day Holters every three months, which is good, but it’s not the same as continuous monitoring. I sometimes wonder if we’re underestimating AF burden in these trials. But, anyway, the headline here is clear: ablation wins for rhythm control, at least in this population.

Hollie

But, as we’ll see, that’s not the whole story, is it?

Hollie

No, not at all. Because if you look at the secondary outcomes, the lifestyle group actually did brilliantly in other areas. They lost an average of 6.4 kilograms—about 14 pounds—and kept it off for two years. Their HbA1c, which is a marker for blood sugar control, improved significantly. And their fitness, measured by peak oxygen uptake, also went up. These are real, meaningful health gains.

Austin

Yeah, and that’s the bit that really caught my eye. Even though they had more AF episodes, their quality of life scores improved just as much as the ablation group. That’s kind of wild, right? You’d expect more arrhythmia to mean worse quality of life, but it didn’t. It suggests that weight loss and fitness improvements have benefits that go way beyond just suppressing AF.

Hollie

Absolutely. I had a patient—let’s call her Mrs. B—who joined a local walking group. She didn’t lose a dramatic amount of weight, but her HbA1c dropped, and her mood lifted. She still had some AF, but she felt better in herself, more energetic, more connected. Sometimes, the numbers don’t tell the whole story.

Austin

That’s such a good point. And, you know, the trial showed that the ablation group barely lost any weight—just 0.35 kg on average. So, if you ablate someone and don’t address their obesity, you’re only solving part of the problem. From a population health perspective, those metabolic improvements—weight, HbA1c, fitness—probably have bigger long-term implications than just rhythm control alone.

Hollie

And it’s not just about the heart, is it? Higher HbA1c is linked to more cardiovascular events and mortality, and increased body weight is tied to heart failure and all-cause mortality. So, these lifestyle changes are doing a lot of heavy lifting, even if the AF isn’t completely suppressed.

Austin

Yeah, and I think that’s something we’ve touched on in previous episodes—like when we talked about sleep and the heart, or the gut-heart connection. It’s all interconnected. Sometimes, the “secondary” endpoints are actually the most important for long-term health.

Hollie

Exactly. And I think the PRAGUE-25 trial really highlights that. Even if you don’t hit the primary endpoint, you can still make a huge difference to someone’s overall health and wellbeing.

Austin

So, let’s talk about what the trial didn’t quite capture. First off, the weight loss in the lifestyle group was decent, but not spectacular—about 6 kilos, which is less than 10% of body weight. Previous studies suggest you need that 10% mark to really see dramatic AF reductions. And, crucially, this trial was done before GLP-1 agonists like semaglutide and tirzepatide became mainstream. If you repeated PRAGUE-25 now, with those drugs, you might see much more weight loss—and maybe different results for AF control.

Hollie

That’s a really important point. GLP-1s can help people lose 10–15% of their body weight, but even in trials with those drugs, the evidence for reducing AF isn’t totally clear yet. Still, they could have boosted all those secondary benefits—weight, glucose, fitness. And another thing: sleep apnea. It wasn’t systematically addressed in PRAGUE-25, but we know that many patients with obesity have sleep apnea, and treating it can help with AF and overall health. So, that’s a bit of a missed opportunity.

Austin

Yeah, and then there’s the issue of antiarrhythmic drugs. The lifestyle group had a sudden cardiac death in a patient on propafenone. It’s a reminder that these drugs aren’t benign, especially in people with obesity. The risk of serious side effects, even sudden death, is real. So, we have to be careful about how we use them.

Hollie

Absolutely. So, where does that leave us? Should we be doing ablation and lifestyle modification together, right from the start? Or is it still reasonable to try lifestyle first, especially now that we have better tools—GLP-1s, digital trackers, sleep interventions?

Austin

I think it’s not an either-or. If someone’s symptomatic and a good candidate, don’t delay ablation just to make them lose weight first—ablation clearly works for rhythm control. But don’t stop there. We need to keep pushing lifestyle changes, maybe add GLP-1s if appropriate, and definitely address sleep and other risk factors. And, honestly, digital tools can help keep patients engaged and give us better data.

Hollie

I agree. The real message from PRAGUE-25 is that we need both: ablation for symptom control and quality of life in the short term, but aggressive lifestyle modification for long-term cardiovascular health. Don’t let perfect be the enemy of good. And as new therapies and tech come along, we’ll need to keep evolving our approach.

Austin

Well said, Hollie. I think that’s a good place to wrap up for today. We’ll be back soon to dig into more edge-of-the-seat cardiology. Thanks for joining me, Hollie.

Hollie

Always a pleasure, Austin. And thanks to everyone listening—don’t forget to look after your hearts, and each other. See you next time!