Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. It occurs in ~1% of the general population. It may cause up to 15% of all strokes and has an associated fivefold increase in embolic stroke of patients without arrhythmias.1 The incidence of heart failure also increases in patients with AF. The two primary arrhythmia management strategies in AF have been rate control (slowing the ventricular response) and rhythm control (converting to sinus rhythm). Previous studies have shown little difference between rate control and rhythm control on complication rates and mortality.2,3 Since rate control is often easier to achieve, it has become the de facto first-line management strategy for most patients. However, the optimum target heart rate in patients with chronic AF has yet to be determined. Some guidelines arbitrarily recommend strict rate control. The Rate Control Efficacy in Permanent Atrial Fibrillation: a Comparison between Lenient verses Strict Rate Control II (RACE II) trial was designed to investigate the effectiveness of a lenient versus a strict rate control plan.4
The RACE II enrolled patients under the age of 80 years (mean 68) with permanent AF, a resting heart rate > 80 beats/min, and the current use of oral anticoagulation or aspirin if no thromboembolic complications were present. Patients were randomly assigned in an open-label fashion to either a lenient rate-controlled strategy (target resting heart rate < 110 beats/min) or a strict rate-controlled strategy (target resting heart rate < 80 beats/min and a target heart rate < 110 beats/min during moderate exercise). Because of the increased risk of bradycardia, the strict control group also underwent 24-hour Holter monitoring after reaching the target heart rate goal and when dose adjustment was required. Patients were given one or more negative dromotropic agents (beta-blockers, nondihydropyridine calcium antagonists, and digoxin) used alone or in combination. Doses were titrated until target heart rate was achieved. The primary outcome was a composite of death from cardiovascular causes, hospitalizations for heart failure, stroke, systemic embolization, or major bleeding, and arrhythmic events including syncope, sustained ventricular tachycardia, cardiac arrest, life-threatening adverse events of rate-control medications, and implantation of a pacemaker or cardioverter-defibrillator.5
A total of 614 patients were enrolled in the trial; 311 in the lenient-control arm and 303 in the strict-control arm. The lenient and strict rate control groups were similar with the exceptions of minor differences in coronary artery disease, statin use, and diastolic blood pressure. The mean resting heart rate at the end of the dose-titration period was 93 beats/min in the lenient rate-control group and 76 beats/min in the strict rate-controlled group (P<0.001). After years one, two and at the end of the follow-up period, the resting heart rates in the lenient rate-control group were 86, 84 and 85 beats/min respectively as compared with 75, 75, and 76 beats/min respectively in the strict rate-controlled group (P<0.001 for all comparisons). During the follow-up period 18 patients in the lenient-control group and 22 patients in the strict-control group converted to normal sinus rhythm.
The primary outcome occurred in 12.9% of the lenient-control and in 14.9% of the strict-control cohorts respectively. Lenient rate control was noninferior to strict rate control with regard to the prevention of the primary outcome. Frequencies of hospitalizations and adverse events were similar between the two groups. Roughly twice as many patients required combination therapy with two or three drugs to reach the goal heart rate in the strict group compared to the lenient group (58.7% vs. 24.2%). Overall, 97.7% of the lenient group reached the target resting heart rate, while only 75.2% of the strict group met the target resting heart rate and 72.6% achieved the exercise heart rate goal. Importantly, it took 684 visits to control 303 patients in the strict group, while it only took 75 visits to control the 311 patients in the lenient group (both groups had similar levels of monotherapy and combination therapy before the beginning of the study).
These data indicating noninferiority in relation to major clinic events between strict and lenient rate control in patients with AF are consistent with a post hoc analysis of the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM)6...