Effectiveness and safety of early treatment with spironolactone for new‐onset acute heart failure

Abstract Background The effectiveness and safety of mineralocorticoid receptor antagonists (MRA) in acute heart failure (HF) is uncertain. We sought to describe the prescription of spironolactone during acute HF and whether early treatment is effective and safe in a real‐world setting. Methods We performed a retrospective cohort study of adult (≥18 years) nonpregnant patients hospitalized with new‐onset HF with reduced ejection fraction (HFrEF, defined by ejection fraction ≤40%) within 15 Kaiser Permanente Southern California medical centers between 2016 and 2021. Early treatment was defined by spironolactone prescription at discharge. The primary effectiveness outcome was a composite of HF readmission or all‐cause mortality at 180 days. Safety outcomes were hypotension and hyperkalemia at 90 days. Results Among 2318 HFrEF patients, 368 (15.9%) were treated with spironolactone at discharge. After 1:2 propensity score matching, 354 early treatment and 708 delayed/no treatment patients were included in the analysis. The median age was 63 (IQR: 52–74) years; 61.6% were male, and 38.6% were White. By 90 days, ~20% had crossed over in the two groups. Early treatment was not associated with the composite outcome at 180 days (HR 95% CI: 0.81 0.56–1.17), but a trend towards benefit by 365 days that did not reach statistical significance (0.78 0.58–1.06). Early treatment was also associated with hyperkalemia (subdistribution HR 95% CI: 2.33 1.30–4.18) but not hypotension (0.93 0.51–1.72). Conclusions Early treatment with spironolactone at discharge for new‐onset HFrEF in a real‐world setting did not reduce the risk of HF readmission or mortality in the first year after discharge. The risk of hyperkalemia was increased.