Table 2.

Key Studies with Mineralocorticoid Receptor Antagonists in Patients with HFmrEF.

Type of Study	Reference	HFmrEF Population	Findings
Post-hoc analysis of randomized clinical trial	Solomon et al., 2016 [27]	520 patients (197 in the Americas) with LVEF 45–50% randomized to placebo or spironolactone, followed for a median of 3.4 years	Patients in this group benefited more from spironolactone; HR for primary endpoint (death or HF hospitalization) was 0.55 (95%CI 0.33–0.91); and for CV death 0.46 (95%CI 0.23–0.94)
Retrospective cohort, China	Xin et al., 2019 [28]	279 HFmrEF patients divided into 3 groups: high-dose (50 mg daily), low-dose (25 mg daily) and no spironolactone	Patients on spironolactone had lower rate of 1-year death or HF rehospitalization vs. untreated (21.3% vs. 34.5%, p = 0.014); no difference between high vs. low dose (21.8% vs. 20.7%, p = 0.861)
Meta-analysis of randomized clinical trials	Xiang et al., 2019 [29]	4539 HFmrEF and HFpEF patients; 375 had myocardial disease, 108 hypertension, and 4056 multiple or unclear etiology; 770 patients with LVEF ≥ 50% and 3769 patients with LVEF ≥ 40% or ≥45%	Spironolactone reduced readmission (odds ratio 0.84; 95%CI 0.73–0.95; p = 0.006) and PICP levels (mean difference, −27.04 ng/mL; 95%CI, −40.77 to −13.32; p < 0.001) in patients with HFmrEF and HFpEF

CV: cardiovascular; HF: heart failure; HR: hazard ratio; LVEF: left ventricular ejection fraction; PICP: procollagen type I C-terminal pro-peptide.