Early Rhythm Control Cuts Event Rate in Afib Patients

Prof. Paulus Kirchhof, MD

Results of the EAST-AFNET 4 study are shedding new light on the beneficial effects of early rhythm control compared against usual care in patients with atrial fibrillation (AF).

An analysis of more than 2500, results of the study suggest initiating a rhythm control intervention within the first year of an AF diagnosis could reduce risk of adverse cardiovascular events by 21% over a 5-year follow-up period.

“Rhythm control therapy initiated soon after diagnosis of atrial fibrillation reduces cardiovascular complications without increasing time spent in hospital and without safety concerns,” said principal investigator Professor Paulus Kirchhof, MD, of the University Heart and Vascular Centre UKE Hamburg, Germany, in a statement from the European Society of Cardiology (ESC). “These results have the potential to completely change clinical practice towards rhythm control therapy early after the diagnosis of atrial fibrillation.”

Presented at ESC Congress 2020, EAST-AFNET 4 was designed to examine whether rhythm control therapy with antiarrhythmic drugs or ablation within the first year following diagnosis could improve outcomes associated with the disease. Conducted at 135 sites, the international, investigator-initiated, parallel-group, open, blinded-outcome-assessment trial randomized 2789 patients to undergo early rhythm control or usual care and was stopped for efficacy at the third interim analysis, which resulted in a median of 5.1 years of follow-up per patient.

Investigators chose a pair of primary efficacy outcomes for their analysis. The first was a composite of deaths from cardiovascular causes, stroke, or hospitalization with worsening heart failure or acute coronary syndrome. The second was the number of nights spent in the hospital per year. For safety, investigators chose a composite of death, stroke, or serious adverse events related to rhythm control therapy as the primary outcome.

For inclusion in the study, patients needed to be at least 18 years of age, have a previous transient ischemic attack or stroke, and meet at least 2 of the following criteria: age greater than 65 years, female sex, heart failure, hypertension, diabetes mellitus, severe coronary artery disease, chronic kidney disease, and left ventricular hypertrophy.

Upon analysis, the first primary outcome event occurred in 249 patients randomized to early rhythm control and 316 patients randomized to usual care (3.9 events per 100 person-years vs 5.0 events per 100 person-years, respectively). Based on these results, investigators determined patients randomized to early rhythm control reduced their risk of such an event by 21% (HR, 0.79; 95% CI, 0.66-0.94; P=.05). The analysis also indicated the mean number of nights spent in the hospital did not differ significantly between the study groups with means of 5.8±21.9 and 5.1±15.5 days per year among the early rhythm control and placebo arms, respectively (P=.23).

In regard to safety, results suggested the rate of primary safety outcome events did not differentiations significantly between the study arms. Investigators pointed out serious adverse events related to rhythm control therapy occurred in 4.9% of patients assigned to rhythm control and in 1.4% of patients assigned to usual care. Additionally, analysis of symptoms and left ventricular function at 2 years indicated no significant difference between the study arms.

This study, “EAST–AFNET 4: Effects of Early Rhythm Control Therapy in Patients with Atrial Fibrillation,” was presented at ESC Congress 2020 and simultaneously published as “Early Rhythm-Control Therapy in Patients with Atrial Fibrillation,” in the New England Journal of Medicine.