Table 1 Open in new tab Major trials of...

Disease state

Major trials of steroidal MRA

Major trials of non-steroidal MRA

HFrEF

RALES³⁷ (n = 1663): Spironolactone reduced all-cause mortality in HFrEF (<35%); RR: 0.70 (95% CI: 0.60, 0.82)
EMPHASIS-HF⁵⁹ (n = 2737): Eplerenone reduced the composite of CV death or HF hospitalization in HFrEF (<35%); HR: 0.63 (95% CI: 0.54, 0.74)

HFpEF

TOPCAT³⁸ (n = 3445): No significant reduction in CV death, aborted cardiac arrest, or HF hospitalization was observed with spironolactone in HFpEF (≥45%); HR: 0.89 (95% CI: 0.77, 1.04)
*A significant reduction in HF hospitalization was observed, and a significant reduction in the primary outcome was observed in sub-group analysis of patients in North/South America³⁹
Ongoing: SPIRRIT-HFpEF⁴⁰: n = 3200 patients with HFpEF (≥40%) planned to be randomized to spironalactone vs. standard of care; primary outcome: CV death or first HF hospitalization
Ongoing: SPIRIT-HF⁴¹: n = 1300 patients with heart
failure with mid-range (40–49%) or preserved (≥50%) ejection fraction planned to be randomized to spironolactone vs. placebo; primary outcome: total CV death and HF hospitalization

Ongoing: FINEARTS-HF¹²⁵: n = 5500 patients with HFpEF (≥40%) planned to be randomized to finerenone vs. placebo; primary outcome: CV death and HF hospitalization

Post-MI

ALBATROSS⁶¹ (n = 1603): Potassium canrenoate followed by spironolactone failed to reduce the risk of death, resuscitated cardiac arrest, significant ventricular arrhythmia, indication for implantable defibrillator, or new or worsening HF in acute MI patients; HR: 0.97 (95% CI: 0.73, 1.28)
REMINDER⁶³ (n = 1012): No significant reduction in CV death, heart failure or sustained ventricular arrhythmia with eplerenone; HR: 0.55 (95% CI: 0.23, 1.35)

Post-MI HFrEF

EPHESUS⁵⁸ (n = 6642): Eplerenone reduced all-cause mortality in post-MI HFrEF (<40%); RR: 0.85 (95% CI: 0.75, 0.96)

Resistant hypertension

PATHWAY-2⁶⁴ (n = 335): Treatment with spironolactone (–8.70 mmHg, 95% CI: −9.72 to −7.69) was superior to treatment with bisoprolol, doxazosin, or placebo for BP reduction on top of three maximally tolerated BP medications in resistant hypertension (with eGFR ≥45 mL/min/1.73 m²)

Ongoing: CLARION-CKD⁸³: n = 600 patients with treatment-resistant hypertension, with 15 ≤ eGFR ≤44 mL/min/1.73 m² on two or more maximally tolerated BP medications will be randomized to KBP-5074 vs. placebo; primary outcome: change in SBP

CKD with diabetes

FIDELIO-DKD¹¹³ (n = 5734): Treatment with finerenone resulted in a lower rate (HR: 0.82, 95% CI: 0.73, 0.93) of the primary renal outcome (kidney failure, a sustained decrease of at least 40% in the eGFR from baseline over a period of at least 4 weeks, or death from renal causes) in CKD patients with either:
1. Persistent albuminuria 30 to <300 mg/g, eGFR 25–59 mL/min/1.73 m², and known diabetic retinopathy OR
2. Persistent albuminuria 300–5000 mg/g and eGFR 25–74 mL/min/1.73 m²
FIGARO-DKD¹¹⁴ (n = 7437): Treatment with finerenone resulted in a lower rate (HR: 0.87, 95% CI: 0.76, 0.98) of the composite of CV death, non-fatal MI, non-fatal stroke, or HF hospitalization in patients with CKD, T2DM, and either:
1. Persistent albuminuria 30 to <300 mg/g, eGFR 25–90 mL/min/1.73 m², and known diabetic retinopathy OR
2. Persistent albuminuria 300–5000 mg/g and eGFR of at least 60 mL/min/1.73 m²
ESAX-DN⁹⁴ (n = 455): Treatment with esaxerenone increased the rate (absolute difference: 18, 95% CI: 12, 25%) of urinary albumin-to-creatinine ratio remission (<30 mg/g creatinine and ≥30% reduction from baseline on two consecutive occasions) in T2DM and a urinary albumin-to-creatinine ratio of 45 to <300 mg/g creatinine.

CKD without Diabetes

Ongoing: FIND-CKD¹²⁴: n = 1580 patients with non-diabetic CKD (25 ≤ eGFR <90 mL/min/1.73 m² and proteinuria/albuminuria) will be randomized to finerenone vs. placebo; primary outcome: rate of change in eGFR

ESRD

Ongoing: ALCHEMIST⁷¹: n = 825 patients on chronic haemodialysis for ESRD regardless of aetiology planned to be randomized to spironolactone vs. placebo; primary outcome: CV death, HF hospitalization, non-fatal stroke, non-fatal MI, or ACS
Ongoing: ACHIEVE⁷⁰: n = 2750 patients on dialysis for ≥90 days planned to be randomized to spironolactone vs. placebo; primary outcome: CV death or HF hospitalization

Disease state

Major trials of steroidal MRA

Major trials of non-steroidal MRA

HFrEF

HFpEF

Ongoing: FINEARTS-HF¹²⁵: n = 5500 patients with HFpEF (≥40%) planned to be randomized to finerenone vs. placebo; primary outcome: CV death and HF hospitalization

Post-MI

Post-MI HFrEF

EPHESUS⁵⁸ (n = 6642): Eplerenone reduced all-cause mortality in post-MI HFrEF (<40%); RR: 0.85 (95% CI: 0.75, 0.96)

Resistant hypertension

CKD with diabetes

CKD without Diabetes

ESRD

Table 1

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Major trials of steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal disease

Disease state	Major trials of steroidal MRA	Major trials of non-steroidal MRA
HFrEF	RALES³⁷ (n = 1663): Spironolactone reduced all-cause mortality in HFrEF (<35%); RR: 0.70 (95% CI: 0.60, 0.82) EMPHASIS-HF⁵⁹ (n = 2737): Eplerenone reduced the composite of CV death or HF hospitalization in HFrEF (<35%); HR: 0.63 (95% CI: 0.54, 0.74)
HFpEF	TOPCAT³⁸ (n = 3445): No significant reduction in CV death, aborted cardiac arrest, or HF hospitalization was observed with spironolactone in HFpEF (≥45%); HR: 0.89 (95% CI: 0.77, 1.04) A significant reduction in HF hospitalization was observed, and a significant reduction in the primary outcome was observed in sub-group analysis of patients in North/South America³⁹ Ongoing: SPIRRIT-HFpEF⁴⁰: n = 3200 patients with HFpEF (≥40%) planned to be randomized to spironalactone vs. standard of care; primary outcome: CV death or first HF hospitalization Ongoing: SPIRIT-HF*⁴¹: n = 1300 patients with heart failure with mid-range (40–49%) or preserved (≥50%) ejection fraction planned to be randomized to spironolactone vs. placebo; primary outcome: total CV death and HF hospitalization	Ongoing: FINEARTS-HF¹²⁵: n = 5500 patients with HFpEF (≥40%) planned to be randomized to finerenone vs. placebo; primary outcome: CV death and HF hospitalization
Post-MI	ALBATROSS⁶¹ (n = 1603): Potassium canrenoate followed by spironolactone failed to reduce the risk of death, resuscitated cardiac arrest, significant ventricular arrhythmia, indication for implantable defibrillator, or new or worsening HF in acute MI patients; HR: 0.97 (95% CI: 0.73, 1.28) REMINDER⁶³ (n = 1012): No significant reduction in CV death, heart failure or sustained ventricular arrhythmia with eplerenone; HR: 0.55 (95% CI: 0.23, 1.35)
Post-MI HFrEF	EPHESUS⁵⁸ (n = 6642): Eplerenone reduced all-cause mortality in post-MI HFrEF (<40%); RR: 0.85 (95% CI: 0.75, 0.96)
Resistant hypertension	PATHWAY-2⁶⁴ (n = 335): Treatment with spironolactone (–8.70 mmHg, 95% CI: −9.72 to −7.69) was superior to treatment with bisoprolol, doxazosin, or placebo for BP reduction on top of three maximally tolerated BP medications in resistant hypertension (with eGFR ≥45 mL/min/1.73 m²)	Ongoing: CLARION-CKD⁸³: n = 600 patients with treatment-resistant hypertension, with 15 ≤ eGFR ≤44 mL/min/1.73 m² on two or more maximally tolerated BP medications will be randomized to KBP-5074 vs. placebo; primary outcome: change in SBP
CKD with diabetes		FIDELIO-DKD¹¹³ (n = 5734): Treatment with finerenone resulted in a lower rate (HR: 0.82, 95% CI: 0.73, 0.93) of the primary renal outcome (kidney failure, a sustained decrease of at least 40% in the eGFR from baseline over a period of at least 4 weeks, or death from renal causes) in CKD patients with either: 1. Persistent albuminuria 30 to <300 mg/g, eGFR 25–59 mL/min/1.73 m², and known diabetic retinopathy OR 2. Persistent albuminuria 300–5000 mg/g and eGFR 25–74 mL/min/1.73 m² FIGARO-DKD¹¹⁴ (n = 7437): Treatment with finerenone resulted in a lower rate (HR: 0.87, 95% CI: 0.76, 0.98) of the composite of CV death, non-fatal MI, non-fatal stroke, or HF hospitalization in patients with CKD, T2DM, and either: 1. Persistent albuminuria 30 to <300 mg/g, eGFR 25–90 mL/min/1.73 m², and known diabetic retinopathy OR 2. Persistent albuminuria 300–5000 mg/g and eGFR of at least 60 mL/min/1.73 m² ESAX-DN⁹⁴ (n = 455): Treatment with esaxerenone increased the rate (absolute difference: 18, 95% CI: 12, 25%) of urinary albumin-to-creatinine ratio remission (<30 mg/g creatinine and ≥30% reduction from baseline on two consecutive occasions) in T2DM and a urinary albumin-to-creatinine ratio of 45 to <300 mg/g creatinine.
CKD without Diabetes		Ongoing: FIND-CKD¹²⁴: n = 1580 patients with non-diabetic CKD (25 ≤ eGFR <90 mL/min/1.73 m² and proteinuria/albuminuria) will be randomized to finerenone vs. placebo; primary outcome: rate of change in eGFR
ESRD	Ongoing: ALCHEMIST⁷¹: n = 825 patients on chronic haemodialysis for ESRD regardless of aetiology planned to be randomized to spironolactone vs. placebo; primary outcome: CV death, HF hospitalization, non-fatal stroke, non-fatal MI, or ACS Ongoing: ACHIEVE⁷⁰: n = 2750 patients on dialysis for ≥90 days planned to be randomized to spironolactone vs. placebo; primary outcome: CV death or HF hospitalization

Disease state	Major trials of steroidal MRA	Major trials of non-steroidal MRA
HFrEF	RALES³⁷ (n = 1663): Spironolactone reduced all-cause mortality in HFrEF (<35%); RR: 0.70 (95% CI: 0.60, 0.82) EMPHASIS-HF⁵⁹ (n = 2737): Eplerenone reduced the composite of CV death or HF hospitalization in HFrEF (<35%); HR: 0.63 (95% CI: 0.54, 0.74)
HFpEF	TOPCAT³⁸ (n = 3445): No significant reduction in CV death, aborted cardiac arrest, or HF hospitalization was observed with spironolactone in HFpEF (≥45%); HR: 0.89 (95% CI: 0.77, 1.04) A significant reduction in HF hospitalization was observed, and a significant reduction in the primary outcome was observed in sub-group analysis of patients in North/South America³⁹ Ongoing: SPIRRIT-HFpEF⁴⁰: n = 3200 patients with HFpEF (≥40%) planned to be randomized to spironalactone vs. standard of care; primary outcome: CV death or first HF hospitalization Ongoing: SPIRIT-HF*⁴¹: n = 1300 patients with heart failure with mid-range (40–49%) or preserved (≥50%) ejection fraction planned to be randomized to spironolactone vs. placebo; primary outcome: total CV death and HF hospitalization	Ongoing: FINEARTS-HF¹²⁵: n = 5500 patients with HFpEF (≥40%) planned to be randomized to finerenone vs. placebo; primary outcome: CV death and HF hospitalization
Post-MI	ALBATROSS⁶¹ (n = 1603): Potassium canrenoate followed by spironolactone failed to reduce the risk of death, resuscitated cardiac arrest, significant ventricular arrhythmia, indication for implantable defibrillator, or new or worsening HF in acute MI patients; HR: 0.97 (95% CI: 0.73, 1.28) REMINDER⁶³ (n = 1012): No significant reduction in CV death, heart failure or sustained ventricular arrhythmia with eplerenone; HR: 0.55 (95% CI: 0.23, 1.35)
Post-MI HFrEF	EPHESUS⁵⁸ (n = 6642): Eplerenone reduced all-cause mortality in post-MI HFrEF (<40%); RR: 0.85 (95% CI: 0.75, 0.96)
Resistant hypertension	PATHWAY-2⁶⁴ (n = 335): Treatment with spironolactone (–8.70 mmHg, 95% CI: −9.72 to −7.69) was superior to treatment with bisoprolol, doxazosin, or placebo for BP reduction on top of three maximally tolerated BP medications in resistant hypertension (with eGFR ≥45 mL/min/1.73 m²)	Ongoing: CLARION-CKD⁸³: n = 600 patients with treatment-resistant hypertension, with 15 ≤ eGFR ≤44 mL/min/1.73 m² on two or more maximally tolerated BP medications will be randomized to KBP-5074 vs. placebo; primary outcome: change in SBP
CKD with diabetes		FIDELIO-DKD¹¹³ (n = 5734): Treatment with finerenone resulted in a lower rate (HR: 0.82, 95% CI: 0.73, 0.93) of the primary renal outcome (kidney failure, a sustained decrease of at least 40% in the eGFR from baseline over a period of at least 4 weeks, or death from renal causes) in CKD patients with either: 1. Persistent albuminuria 30 to <300 mg/g, eGFR 25–59 mL/min/1.73 m², and known diabetic retinopathy OR 2. Persistent albuminuria 300–5000 mg/g and eGFR 25–74 mL/min/1.73 m² FIGARO-DKD¹¹⁴ (n = 7437): Treatment with finerenone resulted in a lower rate (HR: 0.87, 95% CI: 0.76, 0.98) of the composite of CV death, non-fatal MI, non-fatal stroke, or HF hospitalization in patients with CKD, T2DM, and either: 1. Persistent albuminuria 30 to <300 mg/g, eGFR 25–90 mL/min/1.73 m², and known diabetic retinopathy OR 2. Persistent albuminuria 300–5000 mg/g and eGFR of at least 60 mL/min/1.73 m² ESAX-DN⁹⁴ (n = 455): Treatment with esaxerenone increased the rate (absolute difference: 18, 95% CI: 12, 25%) of urinary albumin-to-creatinine ratio remission (<30 mg/g creatinine and ≥30% reduction from baseline on two consecutive occasions) in T2DM and a urinary albumin-to-creatinine ratio of 45 to <300 mg/g creatinine.
CKD without Diabetes		Ongoing: FIND-CKD¹²⁴: n = 1580 patients with non-diabetic CKD (25 ≤ eGFR <90 mL/min/1.73 m² and proteinuria/albuminuria) will be randomized to finerenone vs. placebo; primary outcome: rate of change in eGFR
ESRD	Ongoing: ALCHEMIST⁷¹: n = 825 patients on chronic haemodialysis for ESRD regardless of aetiology planned to be randomized to spironolactone vs. placebo; primary outcome: CV death, HF hospitalization, non-fatal stroke, non-fatal MI, or ACS Ongoing: ACHIEVE⁷⁰: n = 2750 patients on dialysis for ≥90 days planned to be randomized to spironolactone vs. placebo; primary outcome: CV death or HF hospitalization

ACS, acute coronary syndrome; BP, blood pressure; CKD, chronic kidney disease; CI, confidence interval; CV, cardiovascular; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; HR, hazard ratio; MI, myocardial infarction; RR, relative risk; SBP, systolic blood pressure; T2DM, Type 2 diabetes mellitus.

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