Rate control in atrial fibrillation.

Untreated atrial fibrillation is usually associated with a rapid, irregular ventricular response and is often accompanied by symptoms including palpitations, fatigue, dyspnea, and dizziness. It is widely accepted that slowing the ventricular response, both at rest and during activity, with the use of drugs that prolong the refractory period of the atrioventricular (AV) node (so-called rate-control agents) will result in an improvement in symptoms and most likely reduce the future risk of adverse cardiovascular events. The strategy of rate control is preferred by most physicians to the strategy of rhythm control as initial therapy for patients with atrial fibrillation,1 given the failure to show that rhythm-control strategies result in lower rates of death, stroke, or hospitalizations or better quality of life in large, well-conducted, randomized clinical trials.2 When choosing to administer a rate-control agent to a patient, it seems reasonable to attempt to achieve ventricular rates similar to those present during sinus rhythm in patients with a similar degree of heart disease. These targets are based on the belief that lower heart rates will result in fewer symptoms, are likely to be associated with better cardiovascular function because of longer diastolic filling times and more satisfactory hemodynamics, and are associated with a lower risk of tachycardia-related cardiomyopathy. Extrapolation from epidemiologic studies showing that faster heart rates in sinus rhythm are associated with increasing mortality from cardiovascular causes, and the documented clinical and quality-of-life benefits of the “pace and ablate” approach to ventricular rate control,3 also imply that the more closely ventricular rates during atrial fibrillation approximate those during normal sinus rhythm, the better the outcome. These considerations have led to widely adopted guidelines for the ventricular rate targets in patients with atrial fibrillation,4 which recommend resting heart-rate targets of less than 80 beats per minute and targets during moderate physical activity of less than 110 beats per minute. These admittedly arbitrary targets, measured with the use of electrocardiography, are based on the expectation that the benefits of more intensive rate control outweigh its disadvantages and risks. A number of previous lines of evidence, however, suggest possible flaws in the concept of targeting heart rates to near-normal levels. First, the relation between the achieved heart rate and the quality of life or symptoms is inconsistent, and the degree of symptoms during atrial fibrillation is more strongly related to severity of the underlying cardiac disease, age, and sex than it is to heart rate itself.5,6 In retrospective substudies of AFFIRM (the Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial7 and the RACE (Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation) trial,2 in which patients were randomly assigned to undergo a rate-control strategy or a rhythm-control strategy, there was no evidence of a reduction in morbidity or mortality or improved quality of life in patients with “tight” versus “less tight” rate control.6,8 In patients with heart failure, in whom the potential deleterious effects of a high ventricular rate might be particularly prominent, there is no evidence that bisoprolol, as compared with placebo, reduced the rates of death or hospitalization in a subgroup of patients who had atrial fibrillation at baseline.9 In this issue of the Journal, Van Gelder and colleagues report on the RACE II (Rate Control Ef-