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The seemingly eternal debate between rhythm and rate control for atrial fibrillation (AF) matters only for patients with minimal or no symptoms — the very patients enrolled in pertinent comparison trials. (Symptomatic patients seek relief, after all.) AFFIRM was the largest such trial (NEJM JW Cardiol Feb 2003 and N Engl J Med 2002; 347:1825). Now we have data from EAST-AFNET 4 (NCT01288352), a multinational European trial in which 2789 patients (mean age, 70) with recently diagnosed AF (median time from diagnosis, 36 days) were randomized to early rhythm control or usual care (i.e., initial aggressive rate control, with rhythm control for symptoms).
The trial was stopped early, at a median of 5.1 years of follow-up per patient, because incidence of a first-primary-outcome event — cardiovascular death, stroke, or hospitalization with worsening heart failure or acute coronary syndrome — was significantly lower in the rhythm-control group than the usual-care group: 3.9 events (249 patients) versus 5.0 events (316 patients) per 100 person-years. Safety outcomes did not differ significantly between the groups. More than 70% of both groups were asymptomatic at years 1 and 2. Sinus rhythm was more common with rhythm control (85% at 1 year; 82% at 2 years) than with usual care (66% at 1 year; 61% at 2 years).
Kirchhof P et al. for the EAST-AFNET 4 Trial Investigators. Early rhythm-control therapy in patients with atrial fibrillation. N Engl J Med 2020 Aug 29; [e-pub]. (https://doi.org/10.1056/NEJMoa2019422)
Bunch TJ and Steinberg BA.Revisiting rate versus rhythm control in atrial fibrillation— Timing matters. N Engl J Med 2020 Aug 29; [e-pub]. (https://doi.org/10.1056/NEJMe2027180)
Comment
Rhythm control finally wins in minimally symptomatic or asymptomatic AF. Caveats: The rhythm-control strategy was initiated early, before atrial remodeling could occur; most participants remained on anticoagulation therapy; and relatively few participants underwent ablation (about 8% by 1 year, 20% by 2 years). This trial will not dramatically alter my practice, but its findings and those from CABANA (NEJM JW Cardiol Jun 2019 and JAMA 2019; 321:1261) and CASTLE-AF (NEJM JW Cardiol Apr 2018 and N Engl J Med 2018; 378:417) show that normal sinus rhythm matters. Editorialists also note that this trial supports both early rhythm control and the comprehensive management with other cardiovascular therapies that participants received.