The benefit of early rhythm-control therapy

Patients with heart failure and atrial fibrillation can still experience cardiovascular complications, despite being on optimal therapy. Preventing these events represents an unmet need—especially among patients with heart failure and preserved left ventricular ejection fraction (LVEF).

Results from a study published in Circulation suggested that early rhythm-control therapy (ERC) could benefit when started within 1 year of diagnosing atrial fibrillation in patients with signs/symptoms of heart failure.

In the current subanalysis of the randomized EAST-AFNET4 trial (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial), investigators analyzed the effects of systematic, early rhythm-control therapy via antiarrhythmic drugs vs standard care, which permitted rhythm-control therapy to ameliorate symptoms in patients with heart failure. Heart failure was defined as heart failure symptoms per the New York Heart Association II to III or LVEF <50%.

Investigators included 798 participants, with 442 patients exhibiting heart failure with preserved LVEF. Other participants exhibited heart failure with midrange ejection fraction or heart failure with reduced ejection fraction.

The composite primary outcome of cardiovascular death, stroke, or hospitalization secondary to worsening of heart failure or acute coronary syndrome occurred frequently in patients receiving ERC vs those receiving usual care with 5.7 cases per 100 patient-years vs 7.9 cases per 100 patient-years, respectively. The primary safety outcome of death, stroke, or serious adverse events related to rhythm-control therapy occurred in 17.9% of patients with heart failure receiving ERC vs 21.6% of patients receiving usual care. Notably, LVEF improved in both groups, with those in the ERC arm also improving with respect to the composite outcome of death or hospitalization for decompensating heart failure.

The authors wrote that “early rhythm control therapy using antiarrhythmic drugs and atrial fibrillation ablation is safe and reduces cardiovascular outcomes in patients with atrial fibrillation and heart failure compared with the current strategy of delayed, symptom-directed rhythm control. The clinical benefit of early rhythm control therapy was observed in patients with preserved, midrange, and reduced left ventricular ejection fraction.” They also stated that left ventricular function, symptoms, and quality of life enhanced similarly with both treatment approaches.

In this study, flecainide was utilized in many patients without safety concerns. Treatments were administered in accordance with international atrial-fibrillation guidelines, thus supporting the safe use of antiarrhythmic drugs in this patient population.

Patients receiving ERC were more likely to present in sinus rhythm at 24 months vs those receiving usual care, which was expected by the researchers. Furthermore, the number of patients with atrial fibrillation at 2 years was greater in the current subanalysis vs the entire EAST-AFNET4 trial cohort, which was in line with previously published results. The authors suggested that this finding occurred because heart failure is hypothesized to play a role in recurrent atrial fibrillation and atrial cardiomyopathy in those with atrial fibrillation. 

“It seems plausible that early initiation of therapy was one of the factors that rendered antiarrhythmic drug therapy relatively effective in this analysis,” wrote the authors. “Catheter ablation of atrial fibrillation improves quality of life and reduces arrhythmia recurrence to a higher extent than antiarrhythmic drug therapy, with signals that there may be clinical benefit, especially in patients with reduced left ventricular function.”

Limitations of the study include it not being sufficiently powered for subanalysis. Furthermore, EAST-AFNET4 is a strategy trial, with interventions unblinded and no data available regarding left ventricular function or quality of life beyond the 2-year follow-up period. 

Despite these limitations, the researchers highlighted that this analysis is the first contemporary comparison of systematic ERC therapy vs restricted and delayed rhythm control in those with atrial fibrillation and heart failure. Additionally, the size of the population is larger than most randomized trials. Finally, the control group was administered treatment per contemporary atrial fibrillation guidelines, which is also a strength.