Real-world effectiveness of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction: a retrospective, non-interventional cohort analysis

Mineralocorticoid receptor antagonists (MRAs) have been shown in clinical trials to improve outcomes in heart failure with reduced ejection fraction (HFrEF). Yet, it is still uncertain how effective they are in real-world patients with HFrEF. This study aimed to investigate the association between MRAs and outcomes in the overall population and a propensity score-matched cohort, based on patient-level data from the Swedish Heart Failure Registry (SwedeHF). Patients diagnosed with HFrEF were included from the SwedeHF spanning from 2003 to 2020. Enrollment was based on medication dispensation within 3 months before and 6 months after the index date recorded in the register. Endpoints included all-cause mortality, cardiovascular death, and hospital re-admissions, tracked from the index date until censoring or occurrence of an event. Of 47,103 patients identified through the SwedeHF with HFrEF, 22,368 individuals were not treated with MRA (referred to as MRA naive patients), 21,893 were treated with MRA at a dosage of 25 mg, and 1,423 were treated with MRA at 50 mg once daily. In the overall cohort, the administration of MRA at 25 mg was associated with modest reductions in the risk of all-cause mortality (hazard ratio: 0.92 [0.89–0.95], P < 0.0001) and cardiovascular death (hazard ratio: 0.93 [0.89–0.98], P < 0.01) compared to the MRA naive group. However, both dosages of MRA (25 and 50 mg) were associated with a slight increase in the risk of hospital re-admissions due to heart failure 10% compared to MRA naive patients. These findings were consistent when examining a propensity score-matched cohort. Interaction analysis showed a significantly improved survival rate for patients receiving MRA at 25 mg compared to MRA naive individuals, particularly among those with an estimated glomerular rate ≥30 mL/min/1.73 m2 across all patients and in those aged 70 years and above. The administration of MRA treatment at 25 mg once daily was linked to a modestly improved survival in a real-life HFrEF population, with even more pronounced benefits observed within a specific subgroup. This finding highlights the importance of personalized medicine in providing customized therapeutic advantages.