Major Finding: At 3 years, the composite end point occurred in 13% of the lenient rate control group compared to 15% of those assigned to strict rate control, meaning the lenient rate control strategy was statistically noninferior.
Data Source: RACE II randomized 614 patients with permanent atrial fibrillation at 33 Dutch medical centers to strict or lenient rate control to be achieved with beta-blockers, calcium channel blockers, and/or digoxin.
Disclosures: The RACE II trial was supported by the Netherlands Heart Foundation and unrestricted grants from seven pharmaceutical companies. Dr. Van Gelder disclosed serving as a consultant to Sanofi-Aventis, Boehringer Ingelheim, and Cardiome. Dr. Dorian is a consultant to those companies as well as St. Jude Medical.
ATLANTA — A lenient heart rate target of less than 110 bpm at rest in patients with permanent atrial fibrillation is as effective in preventing cardiovascular morbidity and mortality as is the tight rate control strategy recommended in current guidelines, and far more convenient both for patients and physicians, according to a new study.
“Our study suggests that lenient rate control may be adopted as the first-choice rate control strategy in patients with permanent atrial fibrillation, and this applies both for high- and low-risk patients. … If a patient comes into the office with permanent atrial fibrillation, a target resting heart rate just under 110 bpm on a 12-lead ECG is good enough,” Dr. Isabelle C. Van Gelder said in presenting the findings of the Rate Control Efficacy in Permanent Atrial Fibrillation: a Comparison Between Lenient Versus Strict Rate Control II (RACE II) trial at the annual scientific session of the American College of Cardiology.
Based upon the results of earlier clinical trials, most physicians have adopted a strategy of rate control over rhythm control as initial therapy for patients with atrial fibrillation. And the most widely employed rate control strategy today is the one recommended in the current ACC/American Heart Association/European Society of Cardiology guidelines: strict rate control with a resting heart rate below 80 bpm and a heart rate less than 110 bpm during moderate exercise.
The assumption underlying the guideline-recommended strict rate control strategy—one that is not evidence based—has been that a lower heart rate target should result in fewer symptoms and a lower cardiovascular event rate. RACE II shows that assumption is incorrect, according to Dr. Van Gelder of the University of Groningen (the Netherlands).
RACE II randomized 614 patients with permanent atrial fibrillation at 33 Dutch medical centers to strict or lenient rate control to be achieved with beta-blockers, calcium channel blockers, and/or digoxin. The primary study end point was a composite of cardiovascular death, heart failure hospitalization, stroke, systemic embolism, life-threatening arrhythmia, and bleeding. At 3 years of follow-up, the composite end point occurred in 13% of the lenient rate control group compared to 15% of those assigned to strict rate control, meaning the lenient rate control strategy was statistically noninferior. The lenient rate control approach was similarly effective in patients at high baseline cardiovascular risk—those with a CHADS2 score of 2 or more—and in those at lower risk.
Ninety-eight percent of patients in the lenient control group met their heart rate target, as did 67% in the strict control group. The lenient control group collectively had 75 outpatient visits related to atrial fibrillation; the strict control group had 684. A total of 207 (68%) of the 303 patients in the strict rate control group were treated with two or three rate control drugs, compared with 93 (30%) of the 311 patients in the lenient control arm. The dosages required in the strict control arm were about one-third higher, as well.
At the end of follow-up, 46% of patients in each study arm had atrial fibrillation symptoms, 70% were in NYHA functional class I, and 23% were in class II.
Dr. Van Gelder said she and her coinvestigators were concerned that the lenient rate control group would have a higher incidence of heart failure due to tachycardia-mediated cardiomyopathy. That did not transpire. Heart failure rates in the two study arms were similar.
“I think the explanation is that a resting heart rate just below 110 bpm is not high enough to cause tachycardia-mediated cardiomyopathy. Or else it may not be the higher heart rate but the irregular rhythm that's the major cause of heart failure, and the irregular rhythm rate was the same in both groups,” she noted.
Simultaneously with Dr. Van Gelder's presentation in Atlanta, the RACE II results were published online (N. Engl. J. Med. 2010 March 15 [10.1056/NEJMoa1001337]). In an accompanying editorial, Dr. Paul Dorian of the University of Toronto stressed that “the RACE II study does not suggest that ventricular rate control is not needed, only that the conventional therapeutic target needs to be reassessed. At a minimum, the study indicates that reflexive, 'recipe-based' adherence to a rate control target does not seem sensible. … This important study serves as a reminder that it is better to treat the patient and not the electrocardiogram” (N. Engl. J. Med. 2010 March 15 [10.1056/NEJMe1002301]).