Comparative analysis of mineralocorticoid receptor antagonists and renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitor in heart failure with mildly reduced ejection fraction

Introduction: To clarify the efficacy of mineralocorticoid receptor antagonists (MRA) and renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI) in heart failure with mildly reduced ejection fraction (HFmrEF). Methods: This study assessed the association between these medications and outcomes in HFmrEF using data from the National Taiwan University Hospital-integrated Medical Database. The primary outcome was cardiovascular mortality/heart failure hospitalization (HHF). Inverse probability of treatment weighting balanced baseline patient characteristics. The exposure of primary interest was use of MRA and use of RASI/ARNI, while the non-user group was also likely to receive other heart failure medication treatment. Results: Among 2,584 HFmrEF patients, 17% received MRA and 43% received RASI/ARNI. Predictors of MRA use included older age, slightly higher ejection fraction, and lower NT-proBNP level. RASI/ARNI use was predicted by higher BMI, lower NT-proBNP level, normal uric acid and potassium levels. MRA use was not associated with a lower risk of cardiovascular death hazard ratio = 0.89, 95% confidence interval (CI): 0.78-1.02 or HHF (hazard ratio = 1.01, 95% CI: 0.94-1.09). Conversely, RASI//ARNI use was linked to a lower risk of cardiovascular death (hazard ratio = 0.82, 95% CI: 0.71-0.94) but not HHF (hazard ratio = 0.995, 95% CI: 0.924-1.07). Landmark analysis showed no significant difference in outcomes for follow-up durations exceeding 2 years. Conclusion: MRA had a neutral effect on cardiovascular death and HHF, while RASI/ARNI was associated with a lower risk of cardiovascular death. RASI/ARNI may be more beneficial than MRA for HFmrEF patients. Regular re-evaluation is essential to adjust heart failure treatment.