Rhythm control therapy is usually delayed unless patients have persistent symptoms on otherwise effective rate control. However, according to EAST-AFNET 4’s Principal Investigator, Professor Paulus Kirchhof (University Heart and Vascular Center, Hamburg, Germany and University of Birmingham, UK), “The risk of severe cardiovascular complications and death in patients with AF is highest in the first year after diagnosis, suggesting that early therapy could be most beneficial.” He continued, “AF causes atrial damage within a few weeks of disease onset – early rhythm control therapy could reduce or prevent this damage, making it more effective.”
The international investigator-initiated EAST-AFNET 4 trial randomised 2,789 patients in the first year of AF diagnosis with additional risk factors for stroke to either early rhythm control therapy or usual care. Early rhythm control comprised antiarrhythmic drugs or catheter ablation, at the discretion of the local study teams. Rhythm control therapy was escalated when recurrent AF was documented clinically or by ECG. Usual care comprised rate control, with rhythm control therapy being reserved for severe AF-related symptoms despite optimal rate control. Both groups received guideline-recommended treatment for cardiovascular conditions, anticoagulation and rate control.
After a median follow-up of 5.1 years, the first primary outcome of cardiovascular death, stroke, worsening heart failure and acute coronary syndrome occurred less frequently with early rhythm control compared with usual therapy (249 vs. 316 patients; hazard ratio [adjusting for the group-sequential design of the trial] 0.79; 95% confidence interval 0.67–0.94; p=0.005). An absolute risk reduction of 1.1%/year with early rhythm control was noted. The clinical benefit of early rhythm control compared with usual care was consistent across subgroups. Moreover, all components of the primary outcome occurred numerically less frequently, with significant reductions in cardiovascular death and stroke.
There was no difference in the second primary outcome of nights spent in hospital between the early therapy and usual care groups (5.8 ± 21.9 days/year and 5.1 ± 15.5 days/year, respectively; p=0.226). Furthermore, the safety composite of stroke, all-cause death and serious adverse events was similar between the groups (early therapy, 231 events; usual care, 223 events). Rhythm control therapy-related complications were more common in patients on early therapy, but were infrequent and in line with results from other recent rhythm control trials.
“Rhythm control therapy initiated soon after diagnosis of AF reduces cardiovascular complications without increasing time spent in hospital and without safety concerns,” concluded Prof. Kirchhof. “These results have the potential to completely change clinical practice towards rhythm control therapy early after the diagnosis of AF.”