Analysis of randomized controlled trials on the effect of magnitude of heart rate reduction on clinical outcomes in patients with systolic chronic heart failure receiving beta-blockers.

Beta blockers improve cardiac function and prolong survival in patients with systolic chronic heart failure (CHF). However, the exact mechanisms underlying these benefits are uncertain. Specifically, it is unclear whether a close relation exists between heart rate (HR) reduction and clinical outcomes with these agents. This hypothesis was therefore tested within randomized controlled trials of beta blockers in systolic CHF. Left ventricular ejection fraction (LVEF) and HR values at baseline and study end were obtained from available beta-blocker randomized clinical trials. The relation between change in HR and all-cause mortality as well as the LVEF was determined using regression analysis. Thirty-five trials, which included 22,926 patients with a mean follow-up duration of 9.6 months, were analyzed for all-cause mortality, the LVEF, and HR. There was a close relation between all-cause annualized mortality rate and HR (adjusted R2 = 0.51, p = 0.004). A strong correlation between change in HR and change in LVEF (adjusted R2 = 0.48, p = 0.000) was also observed. When only trials with >100 patients were included, an even tighter correlation was seen (adjusted R2 = 0.60, p = 0.0004). In conclusion, these analyses indicate that a major contributor to the clinical benefits of beta-blocker therapy in systolic CHF may be the HR-lowering effect of these agents. Therefore, the magnitude of HR reduction may be more important than the achievement of target dose in beta-blocker treatment of systolic CHF.