Aims Clinical practice guidelines restrict rhythm control therapy to patients with
symptomatic atrial fibrillation (AF). The EAST-AFNET 4 trial demonstrated that early,
systematic rhythm control improves clinical outcomes compared to symptom-directed
rhythm control. Methods and results This prespecified EAST-AFNET 4 analysis compared
the effect of early rhythm control therapy in asymptomatic patients (EHRA score I)
to symptomatic patients. Primary outcome was a composite of death from cardiovascular
causes, stroke, or hospitalization with worsening of heart failure or acute coronary
syndrome, analyzed in a timeto-event analysis. At baseline, 801/2633 (30.4%) patients
were asymptomatic [mean age 71.3 years, 37.5% women, mean CHA(2)DS(2)-VASc score 3.4,
169/801 (21.1%) heart failure]. Asymptomatic patients randomized to early rhythm control
(395/801) received similar rhythm control therapies compared to symptomatic patients
[e.g. AF ablation at 24 months: 75/395 (19.0%) in asymptomatic; 176/910 (19.3%) symptomatic
patients, P= 0.672]. Anticoagulation and treatment of concomitant cardiovascular conditions
was not different between symptomatic and asymptomatic patients. The primary outcome
occurred in 79/395 asymptomatic patients randomized to early rhythm control and in
97/406 patients randomized to usual care (hazard ratio 0.76, 95% confidence interval
[0.6; 1.03]), almost identical to symptomatic patients. At 24 months follow-up, change
in symptom status was not different between randomized groups (P = 0.19). Conclusion
The clinical benefit of early, systematic rhythm control was not different between
asymptomatic and symptomatic patients in EAST-AFNET 4. These results call for a shared
decision discussing the benefits of rhythm control therapy in all patients with recently
diagnosed AF and concomitant cardiovascular conditions (EAST-AFNET 4; ISRCTN04708680;
NCT01288352; EudraCT2010-021258-20). [GRAPHICS] .
