Beta-blocker therapy should be administered to patients with heart failure, <50% left ventricular ejection fraction (LVEF), and sinus rhythm, even in with the presence of moderate or moderately severe renal dysfunction, according to a study published in the Journal of the American College of Cardiology.

Individual patient data from 10 separate placebo-controlled trials were analyzed. To be included, the trials were required to have >300 patients, not be confounded by investigation of other treatments, have a planned follow-up >6 months, and explicitly report mortality as an end point. Only patients with a baseline creatinine reported and LVEF <50% were included (n=16,740). Outcomes were analyzed using a Cox proportional hazards model, stratified by study and grouped by heart rhythm and estimated glomerular filtration rate (eGFR). Interactions between continuous eGFR and mortality or β-blocker efficacy were analyzed with cubic splines.

The median patient age was 65 years, 23% were women, and median LVEF was 27%. Baseline median eGFR was 63 ml/min/1.73 m²; 10.6% of patients had an eGFR >90 ml/min/1.73 m², and only 2.7% of patients had an eGFR <30 ml/min/1.73 m², as a result of the exclusion criteria. The 13,861 patients in sinus rhythm had better renal function at baseline than participants with atrial fibrillation (n=2879).


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eGFR was associated with all-cause mortality independent of other variables, with a 12% increase in the hazard of death for every 10 ml/min lower eGFR (95% CI, 10%-15%; P <.001; median follow-up, 1.3 year). Anemia was associated with higher mortality in the subset of 9906 patients with hemoglobin values compared with patients with no anemia (hazard ratio, 1.35; 95% CI, 1.22-1.50; P <.001). In the subset of patients in sinus rhythm, β-blocker treatment was associated with reduced mortality (hazard ratio, 0.71; 95% CI, 0.66-0.78; P <.0001). This result included patients with moderate and moderately severe renal dysfunction. No deterioration in renal function over time was detected in patients with moderate or moderately severe renal impairment.

The efficacy of β-blockers in patients with sinus rhythm and moderate to moderately severe renal impairment was not affected by anemia, proteinuria, LVEF, or additional adjustment. In patients with atrial fibrillation at baseline, there was no significant reduction in deaths in any category of eGFR and no interaction between β-blocker efficacy and continuous eGFR. Only a small decrease in mean eGFR was noted overall from baseline to the last available measurement; eGFR was 2.0 ml/min/1.73 m² lower after a median of 1.2 years for the 7420 surviving patients in sinus rhythm. In patients with moderate to moderately severe renal impairment at baseline, an increased eGFR of 1.3 ml/min/1.73 m² was detected.

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Study limitations include variation in inclusion criteria among the original studies that gathered individual patient data, low statistical power of interaction tests, and the lack of standardized creatinine measurements for all patients.

“Combining double-blind, individual patient-level data has provided a sufficient sample size to confirm the efficacy of beta-blockers in heart failure patients with reduced ejection fraction, sinus rhythm and renal dysfunction, including those with eGFR 30 to 44 ml/min/1.73 m², the lowest range of eGFR tested in large placebo-controlled trials,” concluded the study authors.

Disclosure: Several study authors declared associations with the pharmaceutical industry. Please see original reference for a full list of authors’ disclosures.

Reference

Kotecha D, Gill SK, Flather MD, et al. Impact of renal impairment on beta-blocker efficacy in patients with heart failure. J Am Coll Cardiol. 2019;74(23):2893-2904.