Table. Summary of Selected Recent or Pending Heart Failure with Preserved Ejection Fraction Randomized Controlled Trials.

Trial	Intervention	HFpEF patient type*	Primary endpoint	Trial result	Trial “Matched” for Rx?
Kosmala et al.	Ivabradine	Exercise-induced DD	Peak VO2, peak E/e’	Positive	Yes
CHAMPION	CardioMEMS sensor	Volume overload	HF hospitalization	Positive	Yes
Guazzi et al.	Sildenafil	Right heart failure / PH	Pulmonary hemodynamics, RV performance, QoL	Positive	Yes
Kitzman et al.	Exercise training	Exercise-induced DD	Peak VO2	Positive	Yes
PARAMOUN T	LCZ696 (ARNI)	Volume overload	ΔNT-proBNP	Positive	Yes
TOPCAT	Sprionolactone	Volume overload	CV death, aborted cardiac arrest, or HF hospitalization	Pending	Yes‡
ALDO-DHF	Spironolactone	Exercise-induced DD	Peak VO2, ΔE/e’	Negative†	No‡
ELANDD	Nebivolol	Exercise-induced DD	6-minute walk test	Negative	No§
J-DHF	Carvedilol (low-dose)	Exercise-induced DD / volume overload	Death or HF hospitalization	Negative	No§
RAAM-PEF	Eplerenone	Volume overload	6-minute walk test	Negative	No‡
RELAX	Sildenafil	Volume overload	Peak VO2	Negative	No

HFpEF = heart failure with preserved ejection fraction; Rx = treatment; ARNI = angiotensin receptor-neprilysin inhibitor; DD = diastolic dysfunction; PH= pulmonary hypertension; HF = heart failure; RV = right ventricle; QoL = quality of life; NT-proBNP = change in N-terminal pro-B-type natriuretic peptide; CV = cardiovascular

^*HFpEF patient types include exercise-induced diastolic dysfunction (ambulatory patients with NYHA class II-III symptoms, grade I diastolic dysfunction, and normal or near-normal BNP levels); chronic volume overload (NYHA class II-IV symptoms with history of heart failure hospitalization, elevated BNP, and/or left atrial enlargement); and associated right heart failure / pulmonary hypertension (NYHA class III-IV symptoms with evidence of pulmonary vascular disease and/or right ventricular dysfunction). See also Figure for examples of each patient type.

^†ALDO-DHF had co-primary end-points and was negative for the peak VO₂ endpoint but positive for the ΔE/e’ endpoint.

^‡Prior HF trials of mineralocorticoid receptor antagonists have shown that these drugs reduce volume overload and improve symptoms, but they do not improve exercise capacity or functional class.

^§Given the vasodilating effects of nebivolol and carvedilol, ELANDD and J-DHF may have been better suited with chronic volume overload type of patients with HF hospitalization as an endpoint; J-DHF may have proven to be positive if higher doses of carvedilol were used in the study.