Table 3.

Main randomized clinical trials on MRAs in patients with HFpEF with improved secondary endpoints but no clear effect on CV deaths.

Study	Year	Drugs	Patients	EF	Primary endpoint	p-value	Follow-up
ALDO-HF	2013	Spironolactone vs. placebo	422	$\ge$50%	Change in diastolic function (E/e’).	p 0.001	12 months
					Change in peak oxygen uptake on cardiopulmonary exercise testing [77]	p = 0.81
TOPCAT	2014	Spironolactone vs. placebo	3445	$\ge$45%	Composite of death from CV causes, aborted cardiac arrest, or hospitalization for HF [79]	p = 0.014	3.3 years
STRUCTURE	2016	Spironolactone vs. placebo	150	$>$50%	Improvement in peak oxygen uptake.	p 0.001	6 months
					Improvement exertional E/e’ ratio [80]	p 0.001
SPIRRIT-HF	On going	Spironolactone vs. no spironolactone	2000	$\ge$40%	Incidence rate for total HF hospitalizations or CV death [82]		5 years
SPIRIT-HF	On going	Spironolactone vs. placebo	1300	$\ge$40%	Cumulative number of primary composite events of CV death and total HF hospitalizations [83]		48 months
FINEARTS-HF	On going	Fineronone vs. placebo	6016	$\ge$40%	Number of CV deaths and HF events [87]		42 months

CV, cardiovascular; EF, ejection fraction; HF, heart failure; MRAs, mineralocorticoids antagonists; HFpEF, heart failure with preserved ejection fraction; ALDO-HF, Aldosterone Receptor Blockade in Diastolic Heart Failure; TOPCAT, Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist; STRUCTURE, Spironolactone in Myocardial Dysfunction with Reduced Exercise Capacity; SPIRRIT-HF, Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction; SPIRIT-HF, Spironolactone In The Treatment of Heart Failure; FINEARTS-HF, Finerenone in Heart Failure Patients; E/e’, spironolactone improved diastolic function.