Heart rate achieved or beta-blocker dose in patients with chronic heart failure: which is the better target?

To investigate whether the mortality of patients with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD) is more strongly related to beta-blocker dose or to heart rate. It is known that beta-blockers reduce mortality in patients with CHF and LVSD, but the primary mechanism of action is uncertain. Patients with an ejection fraction 40, who were in sinus rhythm both at an initial (visit 1) and at a 4-month clinic review (visit 2), were followed for a maximum of 36 months. The relationships between heart rate, beta-blocker dose, and survival in a multivariable model were examined. Of 654 eligible patients, 381 (58) were started on beta-blockers prior to the initial visit, increasing to 537 (82) by visit 2. During follow-up, 142 (22) patients died. Neither resting heart rate nor beta-blocker dose at visit 1 predicted mortality (P 0.09 and P 0.99), but resting heart rate at visit 2 did (P 0.02). Beta-blocker use at visit 2 was associated with better outcome (P 0.03) but with little variation in outcome according to dose. Patients with a heart rate of 5864 b.p.m. at visit 2 had the best prognosis. The use of beta-blockers and resting heart rate at visit 2 both independently indicated prognosis, but beta-blocker dose did not. Beta-blockers may reduce mortality by several mechanisms; one that may be specific to blockade of adrenergic receptors and another related to heart rate reduction. Achieving a target heart rate range may be an appropriate therapeutic goal for patients with CHF.