Conference Coverage

Preventive upstream therapy prevents progression of atrial fib



– Aggressive treatment of known risk factors for atrial fibrillation resulted in improved 1-year maintenance of sinus rhythm in patients with recent-onset atrial fibrillation and heart failure in the randomized multicenter RACE 3 trial, Isabelle C. van Gelder, MD, reported at the annual congress of the European Society of Cardiology.

“We now screen for AF, making it possible to catch patients early. That’s what we’ve learned from this trial: if we start treating patients after their first episode of AF and aggressively reduce risk factors for AF, it may help the sinus rhythm. I think that’s an important message: do not wait too long, start treatment early,” said Dr. van Gelder, professor of cardiology at the University of Groningen, the Netherlands.

She calls the interventional strategy tested in RACE 3 “risk factor-driven upstream therapy.” The four-pronged strategy consisted of statin therapy, a mineralcorticoid receptor antagonist, an ACE inhibitor and/or an angiotensin receptor blocker, and a 9- to 11-week supervised cardiac rehabilitation program emphasizing lifestyle modification through physical training and dietary changes supported by professional counseling to promote adherence.

“These are interventions designed to improve the atrial substrate,” Dr. van Gelder explained.

RACE 3 (Routine versus Aggressive Upstream Rhythm Control for Prevention of Early Atrial Fibrillation in Heart Failure 3) was a multicenter, randomized, nonblinded clinical trial including 245 patients with, on average, a 3-month history of AF, a 2-month history of persistent AF, and a 2-month history of mild to moderate heart failure, either with preserved or reduced ejection fraction. All participants received guideline-directed rhythm control and heart failure therapies. In addition, half of participants were randomized to the upstream intervention. Three weeks after enrollment, all patients underwent electrical cardioversion.

The primary outcome was maintenance of sinus rhythm at 1 year as determined by 7-day Holter monitoring analyzed in blinded fashion at a central laboratory. The rate was 75% in the upstream intervention group, significantly better than the 63% in controls. This represented a 76% greater likelihood of sinus rhythm at 1 year in the upstream intervention group. They also showed significant reductions in systolic and diastolic blood pressure, N-terminal pro-brain natriuretic peptide, and LDL cholesterol, compared with controls. However, at 1 year, the two groups didn’t differ significantly in body mass index or left atrial volume. The lack of impact on left atrial volume was disappointing, Dr. van Gelder said.

“The remodeling process starts long before the first episode of AF, although we don’t know exactly when. Although we intended to intervene early in the remodeling process, I think we weren’t that early,” according to the cardiologist.

Discussant Josep Brugada, MD, applauded the Dutch investigators for opening the door to evidence-based preventive upstream therapy for AF, which he declared is vital given the worsening AF epidemic.

Dr. Isabelle C. van Gelder, professor of cardiology at the University of Groningen, the Netherlands

Dr. Isabelle C. van Gelder

“In recent years enormous efforts have been put into treating symptoms of AF, but clearly we have failed to control the epidemic of AF in our societies, probably because we’ve been aiming only at treating symptoms, not treating the causes,” observed Dr. Brugada of the University of Barcelona.

He added, however, that the RACE 3 intervention didn’t go far enough.

“It’s a bit of a disappointment that there is no change in BMI seen after 1 year. Zero. That probably means the rehabilitation program wasn’t strong enough. Yet, the study results are positive, so if we used physical training in a stronger way to get a reduction in body weight and BMI, probably the outcome would be even greater,” he said.

To be maximally effective, an upstream intervention for AF should also address two other important risk factors for the arrhythmia: heavy alcohol drinking and obstructive sleep apnea, the electrophysiologist added.

The RACE 3 trial was supported by the Netherlands Heart Foundation and the Netherlands Heart Institute. Dr. van Gelder reported having no relevant financial interests.

Dr. van Gelder discussed the RACE 3 trial and results in a video interview.

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