In patients with nonvalvular AF without preexcitation or heart failure, rate and rhythm control strategies are associated with similar mortality and quality of life. Rhythm control is associated with more frequent adverse events, though it may be appropriate in certain clinical scenarios (e.g., symptomatic patients, those unable to achieve rate control).

This question was studied in AFFIRM,¹ a multicenter, parallel-group, randomized control trial of 4060 patients with nonvalvular AF.
Participants were ≥65 years old and felt to have recurrent AF, risk factors for stroke or death, and need for long-term anticoagulation. Individuals were excluded for contraindications to anticoagulation or inability to tolerate ≥two medications in either treatment strategy. AFFIRM randomized individuals to either a rate or rhythm control strategy. In the rate control group, drugs such as beta-blockers, calcium-channel blockers, or digoxin were used to target heart rates of ≤80 bpm at rest and ≤110 bpm with activity (measured via 6-minute walk test or 24-hr ambulatory ECG). In the rhythm control group, class Ia, Ic, or III antiarrhythmic agents, along with electrical cardioversion, were used to achieve and maintain sinus rhythm. All patients were anticoagulated with warfarin (goal INR 2-3), though at the discretion of their physicians, individuals in the rhythm control group who maintained normal sinus rhythm for ≥4 weeks could discontinue anticoagulation. Individuals in either arm who failed pharmacologic treatment could consider radio-frequency ablation, maze procedure, or pacing techniques. The primary outcome was all-cause mortality. The secondary outcome was a composite of death, disability, stroke, anoxic encephalopathy, major bleeding, and cardiac arrest.

There was no difference between rate and rhythm control strategies in the primary (25.9% vs. 26.7%, HR 1.15, 95% CI 0.99-1.34; P = .08) or secondary (P = .33) outcomes. A subgroup analysis showed that rhythm control was associated with increased risk of death in patients ≥65 years old, with coronary artery disease (CAD), and without heart failure. Rate control was not associated with increased adverse events; notable adverse events in the rhythm control group included increased hospitalization rates (P < .001) and torsade de pointes (P = .007). Caveats include limited generalizability to younger patients and those without stroke risk factors, as well as the exclusion of patients with frequent or severe symptoms deemed unsuitable for rate control.

The 2014 American Heart Association (AHA)/American College of Cardiology (ACC) guidelines² recommend a rate control strategy with a beta-blocker or nondihydropyridine calcium-channel blocker for individuals with paroxysmal, persistent, or permanent AF (class I, level B). Rhythm control remains appropriate for patients who are unable to achieve rate control or who remain symptomatic despite rate control. Additionally, because conversion and maintenance of sinus rhythm is more difficult in individuals who remain in AF, some patients—such as
those who are younger or whose cardiac output is significantly impaired by arrhythmias—may benefit from restoration of sinus rhythm.

A lenient heart rate target of <110 bpm at rest is associated with similar outcomes as a strict target of <80 bpm and is a reasonable target for management of asymptomatic permanent AF in patients with preserved left ventricular (LV) systolic function.

RACE-II³ was a prospective, multicenter, open-label, parallel-group, randomized controlled noninferiority trial that compared lenient versus strict HR control in 614 patients with permanent AF. Participants were ≤80 years old, had a mean resting HR > 80 bpm, and were on either oral anticoagulation or aspirin based on thromboembolic risk factors. Participants were randomized to lenient-control with a target resting HR < 110 bpm versus strict-control with target resting HR < 80 bpm and <110 bpm with moderate exercise. Rate control was achieved with beta-blockers, nondihydropyridine calcium-channel blockers, and digoxin, alone or in combination. The primary outcome was a composite of cardiovascular death, heart failure, hospitalization, stroke, systemic embolism, bleeding, and clinically significant arrhythmic events. Secondary outcomes were components of the primary outcome, along with all-cause mortality, and AF symptoms (e.g., dyspnea, fatigue, palpitations, functional status based on New York Heart Association (NYHA) classification).