Rate control efficacy in permanent atrial fibrillation: successful and failed strict rate control against a background of lenient rate control: data from the rate control efficacy in permanent atrial fibrillation study

Abstract

Rate control is often the therapy of choice for permanent atrial fibrillation. The RACE II study was the first to evaluate the relative efficacy of strict rate control (resting heart rate < 80 bpm and during moderate exercise <110 bpm) versus lenient rate control (resting heart rate <110 bpm) in patients with permanent AF. The study demonstrated that lenient rate control was not only easier to achieve but was non-inferior to strict rate control in reducing symptoms, improving the quality of life, exercise tolerance and survival. However, an important limitation was the marked discrepancy in the number of patients achieving target heart rate (THR), in the two groups. While only 67% achieved THR in the strict rate control group, almost all (98%) achieved THR in the lenient rate control group. Since this could have influenced the outcome in favor of lenient rate control, the present post hoc analysis evaluated differences in outcomes in patients with successful strict (n = 203), failed strict (n = 98), and lenient rate control (n = 307). Patients in the strict rate control group who failed to achieve one of the heart rate criteria were classified as failed strict while the remaining patients were classified as successful strict rate control. Nearly 80% of patients in the failed strict group had resting heart rate >80 bpm at the end of dose-adjustment phase. Reasons for failure to achieve strict rate control included drug-related adverse events in 25% and inability to achieve THR with drugs in another 20% patients. Clinical characteristics and echocardiographic parameters (including left atrial and left ventricular dimensions and baseline EF) were similar amongst the three groups. Mean dosages of rate control drugs (beta blockers, verapamil and digoxin) as well as use of drug combination was significantly higher in successful strict and failed rate control as compared to lenient rate control groups. The number of additional hospital visits at 1 and 2 years of follow up were significantly more common in the successful strict and failed strict compared with the lenient group while there was no difference in additional visits between the successful strict and failed strict groups. The primary outcome (composite of death from cardiovascular causes, hospitalization for heart failure, and stroke, systemic embolism, bleeding, and life-threatening arrhythmic events), all-cause mortality and quality of life scores were not significantly different amongst patients with strict, failed strict or lenient rate control. Separate analysis of patients with EF <40% also revealed no differences in the primary outcome. Whether use of more aggressive measures to achieve strict rate control or longer follow up would reveal any outcome differences remains to be studied further. The study confirms that it is often difficult to achieve strict heart rate control in patients with AF with currently available anti-arrhythmic drugs. Not only do these patients require higher dosages of drugs and drug combinations, but the number of additional hospital visits is also more. Despite achieving pre-specified target heart rate, there was no difference in outcome between successful and failed strict rate control. Therefore a strategy of lenient rate control may continue to be the preferred strategy in patients with permanent AF. However in patients with intolerable rate related symptoms or onset of tachycardiomyopathy, lower heart rate targets may be reasonable.