Lenient vs. Strict Rate Control in Patients with AF
Abstract & Commentary
By John P. DiMarco, MD, PhD, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco is a consultant for Novartis and does research for Medtronic and Guidant.
Source: Van Gelder IC, et al. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med. 2010 (e-published on March 15, 2010).
The Rate Control Efficacy in Permanent Atrial Fibrillation (RACE II) study compared two different strategies for rate control in patients with permanent atrial fibrillation. Patients were eligible for the study if they had relatively recent onset atrial fibrillation (duration less than or equal to 12 months), an age of 80 years or younger, a mean resting heart rate above 80 bpm, and able to take appropriate anticoagulation therapy. Patients were randomly assigned to either a lenient rate control strategy or a strict rate control strategy. Resting heart rates were measured using a standard 12-lead electrocardiogram after two to three minutes of rest in the supine position. In the lenient rate control strategy, subjects had only a target resting heart rate below 110 bpm. Additional monitoring was not performed. In the strict control group, the target resting heart rate was 80 bpm. In addition, heart rate was measured during moderate bicycle exercise, with a target of less than or below 110 bpm during mild exercise. In addition, the strict control group also underwent routine 24-hour Holter monitoring to check for bradycardia. Rate control medications were titrated in both groups during follow-up outpatient visits every two weeks until the target was achieved and then on an annual basis.
The primary outcome was a composite of cardiovascular death, heart failure hospitalization, stroke or systemic embolism, major bleeding, serious arrhythmia, life-threatening adverse effects from the rate control therapy, and the need for implantation of a pacemaker or implantable defibrillator due to bradycardia or arrhythmia. Secondary outcomes were death from any cause, symptoms, and functional status. Outcome events were adjudicated by an events committee that was unaware of the randomized treatment assessments. The trial was designed as a noninferiority trial comparing the two strategies.
The study enrolled 311 patients in the lenient rate control group and 303 patients in the strict rate control group. The clinical characteristics of the two groups were well matched. The average age was 68 + 6 years, and 66% were male. The median duration of atrial fibrillation was three months. Seventy-two percent had undergone a previous electrocardioversion. Hypertension, present in 61%, was the primary cardiac diagnosis. Most patients were in New York Heart Association (NYHA) functional class I (65%), with 30% in functional class II and only 5% in functional class III. The resting heart rate at study entry was 96 + 13 bpm. After dosage adjustment, 98% of the lenient rate control group, compared to 67% in the strict rate control group, met their rate control target. Only 75% of the patients in the strict rate control group met their resting heart rate target, and only 72% met their exercise resting target. In the strict rate control group, Holter monitoring showed a mean heart rate of 78 + 11 bpm. The maximum RR interval observed was 2.3 + 0.6 seconds. In the lenient rate control group, only 75 non-routine visits were required to achieve target; whereas in the strict rate control group, 684 total visits were required. Among the 100 patients who failed to achieve their rate control target in the strict control group, 25 had drug-related serious adverse events, and in 22 the target was impossible to achieve with drug therapy.
Almost 65% of the patients in the lenient rate control group were controlled with one or fewer rate control agents. Beta adrenergic blocking agents were the drugs most commonly effective. In comparison, 67% of the patients in the strict rate control group required more than one agent.
The primary composite endpoint was reached by 38 patients (12.9%) in the lenient control group compared to 43 in the strict rate control group. Mortality was similar in both groups with 17 deaths (5.6%) in the lenient control group at three years compared to 18 deaths (6.6%) at three years in the strict rate control group. There was no significant difference in the prevalence of symptoms. Forty-five percent of patients in the lenient control group had persistent symptoms, compared to 46% in the strict control group. New York Heart Association functional class distribution, the frequency of hospitalizations, and other adverse events were similar between the two groups.
The authors conclude that lenient rate control was not inferior to strict rate control in patients with atrial fibrillation in terms of major clinical events. Lenient rate control strategy is more convenient and requires fewer outpatient visits and follow-up visits.
The AFFIRM trial (N Engl J Med. 2002;347:1825-1833) and the original RACE trial (N Engl J Med. 2002;347:1834-1840) were the two pivotal trials that established that rate control and rhythm control strategies were both valid in patients with atrial fibrillation. Those two studies, however, used different criteria for rate control. The AFFIRM trial used values similar to those in the strict control group, and the RACE trial used values similar to those in the lenient control group in RACE II. The current study shows that, at least within the heart rate limits here, a lenient rate control strategy may be easier to implement with no loss of efficacy.
This conclusion seems justified based only on the major endpoints included in this paper. Substudies from RACE II will deal with symptoms and quality of life, but these data have not yet been reported. Certainly, any approach that makes management of patients with atrial fibrillation easier without doing harm would be useful for clinicians.