Relationship of Beta-Blocker Dose With Outcomes in Ambulatory Heart Failure Patients With Systolic Dysfunction: Results From the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) Trial

Study Questions:

Does beta-blocker dose titration improve outcomes in systolic heart failure (HF)?


This was a secondary analysis of the HF-ACTION cohort, consisting of 2,325 ambulatory HF patients with a left ventricular ejection fraction (LVEF) <35% and New York Heart Association (NYHA) class II-IV symptoms. Beta-blocker dose at baseline and follow-up was standardized to carvedilol equivalents. The primary outcome (all-cause mortality and all-cause hospitalization) was analyzed based on beta-blocker dosing.


The median baseline beta-blocker dose was 38 mg daily, and the most common dose range was 26-50 mg daily (36% of cohort). Over 73% of patients did not change beta-blocker dose during the median 2.5 years of follow-up. There were 1,430 (67%) primary events (death or hospitalization). Higher beta-blocker dose was associated with a slight reduction in the primary endpoint (adjusted hazard ratio [HR], 0.96 [0.93-0.99] per 10 mg increase). Beta-blocker dose was not associated with a significant reduction in all-cause death (n = 307 events, 15%) alone (adjusted HR, 0.97 [0.92-1.03]).


The authors concluded that higher beta-blocker doses in patients with HF lead to a reduction in mortality and hospitalization.


In this analysis, patients who were on higher doses of beta-blockers had slightly better outcomes over 2.5 years of follow-up. Patients who were on higher doses of beta-blockers appeared less ill (trends for longer 6-minute walk distance, less NYHA class III/IV), and it is unclear why physicians did not opt to titrate beta-blockers. Perhaps beta-blocker dose titration will lead to improved HF outcomes. However, since beta-blocker dose was really not titrated in this study, the question remains unanswered.

Keywords: Heart Diseases, Cause of Death, Follow-Up Studies, Carbazoles, Ventricular Function, Left, Cardiomyopathies, Exercise, Stroke Volume, Propanolamines, New York, Heart Failure, Systolic

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