By Tim Drake, PharmD, MBA, BCPS

Assistant Professor of Pharmacy, College of Pharmacy, Roseman University of Health Sciences, South Jordan, UT

Dr. Drake reports no financial relationships relevant to this field of study.

SYNOPSIS: Early use of rhythm control in patients with atrial fibrillation and high cardiovascular risk appears to improve cardiovascular outcomes compared to usual care.

SOURCE: Kirchhof P, Camm AJ, Goette A, et al. Early rhythm-control therapy in patients with atrial fibrillation. N Engl J Med 2020;383:1305-1316.

Rate control is the preferred method of treatment for most patients with atrial fibrillation.1 This recommendation is backed by AFFIRM, a study in which researchers compared rate vs. rhythm control and found no difference between the two methods regarding mortality or stroke. Rate control also was tolerated better.2 Medications used for rhythm control include amiodarone, dofetilide, and sotalol, which can be proarrhythmic.1 Even with current therapy, patients with atrial fibrillation are at higher risk for cardiovascular events. The composite of stroke, acute coronary syndrome, heart failure, and cardiovascular death continues to occur at a rate of 5% per year in patients with atrial fibrillation.3 Additionally, newer medications and improved use of cardiac ablation procedures in the 18 years since the publication of the AFFIRM trial warrant a revisit of rate vs. rhythm.4

EAST-AFTNET 4 was an investigator-initiated, international, randomized, open-label, parallel-group trial that included patients with atrial fibrillation. Participants had been living with atrial fibrillation and other cardiovascular conditions for less than one year. Subjects received either early rhythm control or standard of care. Early rhythm control included cardioversion, antiarrhythmic drugs, or cardiac ablation, with the choice of therapy left up to the treating provider. Standard of care included rate control first, with the option to add rhythm control if the patient remained symptomatic with rate control. The first primary outcome was a composite of stroke, hospitalization because of heart failure, acute coronary syndrome, or cardiovascular death. The second primary outcome was the rate of hospitalizations per year.

The trial ended early after an average follow-up of 5.1 years. The authors randomly assigned 2,789 patients to either group. Of those assigned to rhythm control, 8% received ablation, while 86.8% received a rhythm control medication, with flecainide the most prevalent. At two years, the percentage of patients receiving ablation increased to 19.4%. For rate control, beta-blockers were the most popular treatment (85.5%). Each group exhibited about a 90% anticoagulation rate. The first primary composite outcome occurred in 249 rhythm control patients (3.9/100 person-years) and 316 usual care patients (5.0 per 100 person-years) for a hazard ratio of 0.79 (95% CI, 0.66-0.94; P = 0.005). Hospitalizations did not differ between the two groups. Serious adverse events related to rhythm control therapy happened in 1.4% of usual care patients compared to 4.9% of rhythm control patients. More than 70% of patients in both groups were asymptomatic at two years. Quality of life, left ventricular function, and cognitive function also were equal in both groups.

The authors concluded early initiation of rhythm control may produce fewer cardiovascular events compared to usual care in patients with atrial fibrillation for less than one year who have additional cardiovascular conditions. This therapy comes at a cost, with more serious adverse events.


There are two major goals in treating atrial fibrillation: appropriate anticoagulation to prevent stroke, and ventricular rate control to prevent dilated cardiomyopathy.1 Historically, rhythm control has been used for symptomatic relief. Kirchhof et al uncovered an association between early rhythm control therapy and fewer adverse cardiovascular outcomes, which may boost its use. In contrast to earlier studies, cardiac ablation was included in this study and may have contributed to the favorable results for rhythm control. Instead of trying to decide which is better (rhythm control or rate control), perhaps the better thought process is to realize there are many tools to treat atrial fibrillation. The clinician must choose the right tool that will fit the patient best. Much like a mechanic may switch tools during a job to better suit the situation, a caregiver now has more viable options to help reduce morbidity and mortality associated with atrial fibrillation.


  1. January CT, Wann LS, Alpert JS, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in collaboration with the Society of Thoracic Surgeons. Circulation 2019;140:e125-e151.
  2. Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347:1825-1833.
  3. Marijon E, Le Heuzey J-Y, Connolly S, et al. Causes of death and influencing factors in patients with atrial fibrillation: A competing-risk analysis from the Randomized Evaluation of Long-Term Anticoagulant Therapy study. Circulation 2013;128:2192-2201.
  4. Willems S, Meyer C, de Bono J, et al. Cabins, castles, and constant hearts: Rhythm control therapy in patients with atrial fibrillation. Eur Heart J 2019;40:3793-3799c.