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Why the study?
Kidney dysfunction often leads to reluctance to start or continue life-saving heart failure therapy, creating a need to evaluate the efficacy and safety of MRAs in patients with HFrEF experiencing significant kidney dysfunction.
Does MRA treatment reduce cardiovascular death or HF hospitalization in HFrEF patients who experience a decline in eGFR to <30 mL/min/1.73 m2?
Meta-Analysis (n=4,355)
Yes
Does MRA treatment reduce cardiovascular death or HF hospitalization in HFrEF patients who experience a decline in eGFR to <30 mL/min/1.73 m2?
Effect estimate: HR 0.65 (95% CI 0.43-0.99)
MRA therapy provides a large absolute risk reduction in HFrEF patients even when eGFR declines to <30 mL/min/1.73 m2, suggesting treatment should not be automatically discontinued despite a small increase in severe hyperkalemia.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“A post hoc analysis of the RALES and EMPHASIS HF trials has shown that, although treatment of heart failure with reduced left ventricular ejection fraction in patients with mineralocorticoid receptor antagonists can cause a significant deterioration in renal function, the benefits outweigh the adverse effects and should not lead to automatic therapy discontinuation.”
“In summary, I believe this report serves to encourage us to carefully consider the potential downside to any discontinuation of guideline-directed medical therapy for HF.”
MRA benefit persists with eGFR decline to <30 in HFrEF; confirms efficacy across renal strata in randomized data.
BACKGROUND Kidney dysfunction often leads to reluctance to start or continue life-saving heart failure (HF) therapy. OBJECTIVES This study sought to examine the efficacy and safety of mineralocorticoid receptor antagonists (MRAs) in patients with HF with reduced ejection fraction experiencing significant kidney dysfunction. METHODS We pooled individual patient data from the RALES (Randomized Aldactone Evaluation Study) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) trials. The association between MRA treatment and outcomes was assessed according to whether the estimated glomerular filtration rate (eGFR) declined to <30 mL/min/1.73 m2 or not. The primary outcome was cardiovascular death or HF hospitalization. RESULTS Among 4,355 patients included, 295 (6.8%) experienced a deterioration of eGFR after randomization to <30 mL/min/1.73 m2. These patients had more impaired baseline cardiac and kidney function (eGFR 47.3 ± 13.4 mL/min/1.73 m2 vs 70.5 ± 21.8 mL/min/1.73 m2) and had a higher risk of the primary outcome than patients without eGFR deterioration (HR: 2.49; 95% CI: 2.01-3.08; P < 0.001). However, the risk reduction in the primary outcome with MRA therapy was similar in those who experienced a decrease in eGFR to <30 mL/min/1.73 m2 (HR: 0.65; 95% CI: 0.43-0.99) compared with those who did not (HR: 0.63; 95% CI: 0.56-0.71) (Pinteraction = 0.87). In patients with a decrease in eGFR to <30 mL/min/1.73 m2, 21 fewer individuals (per 100 person-years) experienced the primary outcome with MRA treatment, vs placebo, compared with an excess of 3 more patients with severe hyperkalemia (>6.0 mmol/L). CONCLUSIONS Because patients experiencing a decrease in eGFR to <30 mL/min/1.73 m2 are at very high risk, the absolute risk reduction with an MRA in these patients is large and this decline in eGFR should not automatically lead to treatment discontinuation.
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Matsumoto et al. (2024) conducted a meta-analysis in Heart failure with reduced ejection fraction (n=4,355). Mineralocorticoid receptor antagonists (MRAs) vs. Placebo was evaluated on Cardiovascular death or HF hospitalization (HR 0.65, 95% CI 0.43-0.99).
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