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. This article originally appeared in the May issue of Clinical Cardiology Alert. At that time it was peer reviewed by Ethan Weiss, MD, Assistant Professor of Medicine, Division of Cardiology and CVRI, University of California, San Francisco. Dr. Weiss reports no financial relationship to this field of study.
Synopsis: Lenient rate control was not inferior to strict rate control in patients with AF in terms of major clinical events.
Source: Van Gelder IC, et al. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med 2010;362:1363-1373.
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 (AF, duration ≤ 12 months), an age of 80 years or younger, a mean resting heart rate (HR) > 80 bpm, and an ability 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 2-3 minutes of rest in the supine position. In the lenient rate control strategy, subjects had only a target resting HR < 110 bpm. Additional monitoring was not performed. In the strict control group, the target resting HR was 80 bpm. In addition, HR was measured during moderate bicycle exercise with a target of < 110 bpm during mild exercise. 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 2 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 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 non-inferiority 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. Overall the average age was 68 ± 6 years and 66% were male. The median duration of AF was 3 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 HR 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 HR target and only 72% met their exercise resting target. In the strict rate control group, Holter monitoring showed a mean HR 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. At 3 years, mortality was similar in both groups with 17 deaths (5.6%) in the lenient control group compared to 18 deaths (6.6%) 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. NYHA functional class distribution, the frequency of hospitalizations, and other adverse events were similar between groups.
The authors conclude that lenient rate control was not inferior to strict rate control in patients with AF 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 and the original RACE trial were the two pivotal trials that established that rate control and rhythm control strategies were both valid in patients with AF. 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 AF easier without doing harm would be useful for clinicians.