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Beta-Blockers for HF With Reduced, Mid-Range, and Preserved EF
Study Questions:
What is the effect of beta-blockers according to left ventricular ejection fraction (LVEF) in double-blind, randomized, placebo-controlled trials?
Methods:
The study authors conducted a meta-analysis of 11 randomized clinical trials where they stratified patients by baseline LVEF and heart rhythm. After exclusions, the study cohort included 14,262 patients in sinus rhythm and 3,050 patients in atrial fibrillation (AF), with a mean follow-up of 1.5 years (standard deviation, 1.1) and median follow-up of 1.3 years (interquartile range [IQR], 0.8-1.9). At baseline, median LVEF was 27% (21-33%) and was similar for patients in sinus rhythm and AF. Combining both heart rhythms, 721 patients had an LVEF 40-49% and 317 had an LVEF ≥50%. They used an intention-to-treat analysis to determine the primary outcomes that included all-cause mortality and cardiovascular death over a median 1.3 years of follow-up. They only included unconfounded placebo-controlled trials that recruited >300 patients, with a planned follow-up of >6 months and explicit reporting of mortality.
Results:
Median age of the cohort was 65 (IQR, 55-72) years, 24% were women, and 66% had ischemic heart disease as the cause for HF. Patients with a higher baseline LVEF were older; more likely to be women, have milder New York Heart Association (NYHA) class, and higher blood pressure; and less likely to have ischemic heart disease. Beta-blockers were associated with reductions in all-cause and cardiovascular mortality compared to placebo for patients in sinus rhythm (interaction p > 0.5 for LVEF as a continuous measure). Beta-blockers were effective in all LVEF categories, except in the small subgroup where LVEF was ≥50%. There was no evidence for a difference in benefit when LVEF was 40-49%; all-cause mortality occurred in 21/292 (7.2%) randomized to beta-blockers compared with 35/283 (12.4%) assigned to placebo (adjusted hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.34-1.03), and cardiovascular death in 13/292 (4.5%) with beta-blockers and 26/283 (9.2%) with placebo; (adjusted HR, 0.48; 95% CI, 0.24-0.97). Beta-blockers reduced both sudden death and deaths ascribed to heart failure for patients in sinus rhythm, but had no effect on noncardiovascular mortality. This analysis found a substantial 4.7% absolute reduction in cardiovascular mortality in patients with LVEF 40-49% and sinus rhythm (number needed to treat to prevent one cardiovascular death = 21 during a median follow-up of 1.3 years). This finding was statistically significant despite the relatively low number of trial patients studied in this LVEF category. Despite similar improvements in LVEF seen for those in AF, this did not translate into better outcomes with beta-blockers for patients in AF.
Conclusions:
The authors concluded that beta-blockers improve LVEF and prognosis for systolic HF patients in sinus rhythm. In their cohort, they found that the data were most robust for LVEF <40%, but a similar benefit was observed in the subgroup of patients with LVEF 40-49%.
Perspective:
This is an important study because it suggests that beta-blockers are beneficial in those patients with HF associated with mid-range LVEF (40-49%) and in sinus rhythm. The next step would be to confirm these important findings by conducting prospective randomized clinical trials in HF patients with mid-range LVEF with and without AF.
Keywords: Adrenergic beta-Antagonists, Arrhythmias, Cardiac, Atrial Fibrillation, Blood Pressure, Coronary Artery Disease, Death, Sudden, Heart Failure, Heart Failure, Diastolic, Heart Failure, Systolic, Ischemia, Stroke Volume, Systole
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