Does magnitude of heart reduction influence clinical outcomes in patients with Systolic chronic heart failure receiving beta-blockers? A regression analysis of randomised controlled trials

Background: Beta-blockers (BBs) 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 relationship exists between heart rate (HR) reduction and clinical outcomes with these agents. We therefore tested this hypothesis within randomised controlled trials (RCTs) of BBs in systolic CHF. Methods: Left ventricular ejection fraction (LVEF) and HR values at baseline and end-study were obtained from available BB RCTs. The relationship between change in HR and all-cause mortality as well as LVEF was determined using regression analysis (SPSS). Results: Thirty-six trials, which included 23,122 patients with mean follow-up of 10.5 months, were analysed for all-cause mortality, LVEF and HR. There was a close relationship between all-cause annualised mortality rate and change in HR (adjusted R2=0.51, p=0.004). A strong correlation between change in HR and change in LVEF (adjusted R2=0.47, p=0.000, Figure) was also observed. When only trials with >100 patients were included, an even tighter relationship was seen (adjusted R2=0.60, p=0.0004). Conclusions: These analyses indicate that a major contributor to the clinical benefits of BB therapy in systolic CHF is the HR-lowering effect of these agents. Therefore, magnitude of HR reduction may be more important than achievement of target dose in BB treatment of systolic CHF.