Clinical Question

For older patients at high cardiovascular risk, is a strategy of rate control or rhythm control preferred for recent-onset atrial fibrillation (AF)?

Bottom Line

In high-risk older patients with recent-onset AF, a strategy of rhythm control results in fewer cardiovascular deaths (number needed to treat [NNT] = 333 per year) and fewer strokes (NNT = 333 per year). However, there are more adverse events and complications and a small decrease in health-related quality of life. This is a decision that should be individualized, and these findings should not be extrapolated to younger and lower-risk populations without further evidence. (Level of Evidence = 1b)

Synopsis

Previous studies that compared rate control and rhythm control had mixed results. In this study, 2,789 older adults with an onset of AF within the past year were recruited. Participants had to be older than 75 years, have had a recent transient ischemic attack (TIA) or stroke, or have at least two of the following: older than 65 years, female sex, heart failure or left ventricular hypertrophy, hypertension, diabetes mellitus, chronic kidney disease, or severe coronary disease. At baseline, the mean age of participants was 70 years, 46% were women, 12% had a previous TIA or stroke, 12% had chronic kidney disease, 28% had heart failure, 88% had hypertension, and 44% had valvular heart disease. The groups were balanced at baseline, and analysis was by modified intention to treat of all patients who had at least one follow-up assessment. This was a very high-risk group of patients. The patients were randomized to receive rhythm control using medications or ablation, or rate control to manage symptoms. In the rhythm control group, recurrent AF triggered additional attempts to cardiovert the patient. In the rhythm control group after two years, 19.4% had undergone ablation, 21% were taking flecainide, 17.7% were taking amiodarone or dronedarone (Multaq), and 35% were taking no antiarrhythmic drug. In the rate control group after two years, only 7% had undergone ablation and 5.7% were taking an antiarrhythmic drug. Approximately 90% in both groups were taking anticoagulants after two years. The study was stopped early due to the detection of an efficacy signal after a median follow-up of 5.1 years.

The primary outcome was a composite of two important things (stroke and cardiovascular death) and two less important things (hospitalization for heart failure and hospitalization for acute coronary syndrome). This composite was less likely in the rhythm control group (3.9 vs. 5.0 per 100 person-years; NNT = 90 over five years to prevent one event). The likelihoods of cardiovascular death (1.0 vs. 1.3 per 100 person-years; NNT = 67 over five years) and stroke (0.6% vs. 0.9% per 100 person-years; NNT = 67 over five years) were significantly lower in the rhythm control group, but the magnitude of those benefits was relatively small. Hospitalizations for heart failure and acute coronary syndrome were numerically less likely in the rate control group, but this difference was not statistically significant. The 12-item short-form health survey mental score was significantly lower in the rhythm control group (−1.2 points; 95% CI, −2.04 to −0.37), and patients in that group were significantly more likely to be in sinus rhythm (82.1% vs. 60.5%; P < .05; NNT = 5). Patients in the rhythm control group had significantly more serious adverse events attributed to therapy, such as drug-induced bradycardia, toxicity caused by the antiarrhythmic drugs, pericardial tamponade, or major bleeding. There was no difference in the likelihood of being symptomatic and no difference in hospital days or in other health scores.

Study design: Randomized controlled trial (single-blinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (any)

Reference: Kirchhof P, Camm AJ, Goette A, et al. EAST-AFNET 4 Trial InvestigatorsEarly rhythm-control therapy in patients with atrial fibrillation. N Engl J Med. 2020;383(14):1305–1316.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.