Heart Rate Lowering vs. Beta-Blocker Dose: Is One More Important in HFrEF?
In patients with heart failure with reduced ejection fraction (HFrEF), does reduced heart rate (HR) or higher beta-blocker (BB) dose affect outcomes to a greater extent compared to one another?
This was a post hoc analysis of the HF-ACTION multicenter trial, in which 2,331 ambulatory HF patients with HFrEF were randomized to exercise training (a prescription of supervised aerobic exercise training at 60-70% of HR reserve 3 times per week, followed by home-based training at the same intensity 5 times per week, totaling 36 sessions) or usual care. BB dose at baseline was standardized by use of carvedilol equivalents. Both BB dose and resting HR were analyzed by discrete groups (higher/lower dose; higher/lower HR). The relationship of BB dose, HR, and the primary endpoint of all-cause mortality or all-cause hospitalization and other cardiovascular secondary endpoints were determined in unadjusted analyses and those adjusted for variables found to be significantly associated with the outcome in the HF-ACTION cohort.
There was a significant inverse relationship between either BB dose (higher was better) or HR (lower was better) and all-cause death or hospitalization in unadjusted analysis; however, in adjusted analyses, only higher BB dose remained significantly associated with improved outcomes regardless of high or low HR (hazard ratio, 0.77; 95% confidence interval, 0.70-0.86; p = 0.03). The worst outcomes were associated with low BB dose combined with a high HR. Only BB dose was significantly associated with improved mortality in unadjusted analyses, but this association did not persist after multivariable adjustment.
There is an association between higher doses of beta-blockade and improved all-cause death/rehospitalization, irrespective of baseline HR being high or low.
This is an important analysis, albeit limited somewhat by the small number of events. Nonetheless, the message reinforces the need to titrate BBs to maximal tolerant doses in patients with HFrEF. As the authors emphasize, national guidelines recommend such titration and moderat-e to high-intensity beta-blockade, but often patients’ medications are not titrated to appropriate targets, falling short of therapeutic benefits.
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