Key result
Eplerenone shows no difference versus spironolactone for death or HF hospitalization in new-onset HFrEF.
Why the study?
Eplerenone and spironolactone are beneficial in HFrEF, but had not been prospectively compared.
Does eplerenone improve clinical outcomes compared to spironolactone in patients with new-onset HFrEF?
Cohort (n=7,479)
Yes
Does eplerenone improve clinical outcomes compared to spironolactone in patients with new-onset HFrEF?
In patients with new-onset HFrEF, initiation of eplerenone versus spironolactone is associated with similar clinical outcomes, although eplerenone is associated with lower rates of treatment withdrawal.
Should not alter MRA selection in new-onset HFrEF; leaves open tolerability questions and requires randomized confirmation.
BACKGROUND: The mineralocorticoid receptor antagonists (MRAs) eplerenone and spironolactone are beneficial in heart failure with reduced ejection fraction (HFrEF), but have not been prospectively compared. We compared clinical outcomes, daily dosages, and discontinuation rates for the two drugs in a nationwide cohort. METHODS: We identified all patients with HFrEF in the period 2016-2020, who were alive and had initiated MRA treatment at study start, 180 days after HF diagnosis. We estimated the 2-year risk of a composite of death and HF hospitalization, as well as each component separately, using Kaplan-Meier, cumulative incidence functions, and Cox proportional hazards models adjusted for age, sex, and comorbidities. Secondly, we assessed treatment withdrawal, cross-over, and daily drug dosage. RESULTS: We included 7479 patients; 653 (9%) on eplerenone and 6840 (91%) on spironolactone. Patients in the eplerenone group were younger (median age 65 vs. 69 years), and more often men (91% vs. 68%), both P < 0.001. In adjusted analyses, with spironolactone as reference, there were no differences in the risk of the composite of all-cause death and HF hospitalization (HR 1.02, 95% CI 0.82-1.27), all-cause death (HR 0.93, 95% CI 0.67-1.30), or HF hospitalization (HR 1.10, 95% CI 0.84-1.42). Treatment withdrawal occurred in 34% in the eplerenone group and 53% in the spironolactone group (P < 0.001), treatment cross-over in 3%, and 10%, respectively. Daily dose >25 mg at 12 months, was observed in 230 patients (37%) in the eplerenone group and 771 patients (12%) in the spironolactone (P < 0.001). CONCLUSIONS: In a contemporary nationwide cohort of patients with new-onset HFrEF who initiated MRA, we found no differences in clinical outcomes associated with initiation of eplerenone vs. spironolactone. Treatment was more frequently withdrawn, and daily drug dosage was lower among patients treated with spironolactone.
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Larsson et al. (2023) conducted a cohort in new-onset heart failure with reduced ejection fraction (HFrEF) (n=7,479). Eplerenone vs. Spironolactone was evaluated on composite of all-cause death and HF hospitalization (HR 1.02, 95% CI 0.82-1.27). Initiation of eplerenone versus spironolactone in new-onset HFrEF showed no difference in the composite risk of all-cause death or HF hospitalization (HR 1.02; 95% CI 0.82-1.27).
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