Professor David Brieger: new evidence for early rhythm control in AF

Patients with newly diagnosed atrial fibrillation (AF) benefit from early rhythm control therapy, according to results of the EAST-AFNET 4 trial.

The European study, presented at the ESC Virtual Congress and published in the NEJM, comprised 2,789 from 135 sites in 11 countries.

Patients, with a median of 36 days since AF diagnosis, were randomised to rhythm control therapies – antiarrhythmic drugs or AF ablation – or usual rate control therapy. Most patients also received guideline-recommended anticoagulation and therapy for cardiovascular conditions.

The study found the first primary outcome, a composite of cardiovascular death, stroke, worsening heart failure and acute coronary syndrome, occurred less often in patients on early rhythm control than those receiving usual care (3.9 v 5.0 per 100 person-years; HR 0.79).

The clinical benefit of early rhythm control was consistent across subgroups, including asymptomatic patients, obese patients and patients with or without heart failure.

All components of the primary outcome occurred numerically less often in patients randomised to early therapy, and cardiovascular death and stroke were significantly reduced compared to usual care.

There was no significant difference between the groups in either the second primary outcome of nights spent in hospital per year or the primary safety outcome of a composite of stroke, all-cause death, and serious adverse events likely to be caused by rhythm control therapy.

Most patients were free from AF-related symptoms at two years, and there were no significant differences in LV function, cognitive function, or changes from baseline quality of life scores between the groups.

“Early initiation of rhythm-control therapy was associated with less frequent cardiovascular events than usual care in patients with early atrial fibrillation and cardiovascular conditions without affecting the number of nights spent in the hospital,” the study authors concluded.

Commenting on the study, cardiologist Professor David Brieger, from Concord Hospital and the University of Sydney and lead author on the Australian AF guidelines, told the limbic that current practice was supported by the study.

“I think it’s fair to say that quite commonly when patients have a first episode of AF or relatively recent onset AF, particularly if they are symptomatic, clinicians will attempt some kind of rhythm control strategy, despite the fact the guidelines suggest that may not be necessary. We didn’t have evidence to support it three years ago.”

He said the earlier studies that suggested that rhythm control didn’t work were more than 20 years old now.

“Which is why our guidelines suggested that you individualise your decision.”

He said the European study was a substantive piece of evidence which deserved attention.

“We’ve got a few years yet before we will update our guidelines but I think this study will permeate the cardiology community. And because it in some ways does reflect our practice, it will probably lend some support to what a lot of cardiologists are doing anyway with patients who present with their first episode of AF or with newly diagnosed AF.”

“What this suggests is that in patients, early on in the disease process, you should perhaps be a bit more aggressive in trying to get them into sinus rhythm and maintain it.”

He noted most of the study participants were managed with either flecainide or amiodarone.

“They are tricky drugs to use. But interestingly in this study, yes there were some drug-related side effects and complications documented, but numerically they were very small.”

It suggested that strategies for using antiarrhythmic drugs have improved over the years.

“So the barrier is that patients don’t like to be on drugs and that is always an issue. Amiodarone in particular which was used in about 20% of the patients is a complicated drug and tends to accumulate in various organs so you have to be careful.”

“The other thing that has changed in this study compared to the earlier ones is the availability of ablation. And ablation is an exciting tool which proponents of it are always very quick to point out. But it wasn’t used that commonly in this study – only 8.0% initially and up to 20% at two years.”

“So whilst it is a new tool in our armamentarium that wasn’t available 20 years ago, it wasn’t used in the majority of patients so it is hard to know how much of a contribution it has made to the improvement in outcomes.”

An editorial in the NEJM said the results of the EAST-AFNET 4 trial support the early use of rhythm control to reduce AF-related adverse clinical outcomes.

“The use of other cardiovascular therapies (including anticoagulants, renin-angiotensin-aldosterone system inhibitors, beta-blockers, and statins) in the trial probably contributed to the low rates of stroke, heart failure, acute coronary syndrome, and death and highlight the need to treat atrial fibrillation with comprehensive management,” they added.

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