Table 1. Summary of Clinical Trials.

BNP: brain natriuretic peptide; CAPACITY-HfpEF: A Study of the Effect of IW-1973 on the Exercise Capacity of Patients With Heart Failure With Preserved Ejection Fraction; DILATE: A Study to Test the Effects of Riociguat in Patients With Pulmonary Hypertension Associated With Left Ventricular Diastolic Dysfunction; HF: heart failure; HFpEF: heart failure with preserved ejection fraction; HFrEF: heart failure with reduced ejection fraction; HHF: hospitalization for heart failure; KCCQ: Kansas City Cardiomyopathy Questionnaire; LAV: left atrial volume; LVEF: left ventricular ejection fraction; mPAP: mean pulmonary arterial pressure; NCT: National Clinical Trial; NT-proBNP: N-terminal prohormone of brain natriuretic peptide; PH: pulmonary hypertension; PLS: physical limitation score; sGC: soluble guanylate cyclase; SOCRATES-PRESERVED: Phase IIb Safety and Efficacy Study of Four Dose Regimens of BAY1021189 in Patients With Heart Failure and Preserved Ejection Fraction Suffering From Worsening Chronic Heart Failure; SOCRATES-REDUCED: Phase IIb Safety and Efficacy Study of Four Dose Regimens of BAY1021189 in Patients With Heart Failure With Reduced Ejection Fraction Suffering From Worsening Chronic Heart Failure; VICTORIA: vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction; VITALITY-HFpEF: Patient-reported Outcomes in Vericiguat-treated Patients With HFpEF 

Author	Year	Clinical trial	Trial registration number	No. of patients	Purpose of study	Conclusions
Bonderman et al. [22]	2014	DILATE	NCT 01172756	39	To determine acute hemodynamic effects of riociguat in patients with PH and HFpEF	No significant difference in mPAP was seen between riociguat and placebo. However, riociguat increased the cardiac index.
Gheorghiade et al. [23]	2015	SOCRATES-REDUCED study	NCT 01951625	351	To determine optimal dose and tolerability of vericiguat in HFrEF patients	Vericiguat was well-tolerated and higher doses were associated with a greater reduction in NT-pro BNP level
Pieske et al. [24]	2017	SOCRATES-PRESERVED study	NCT 01951638	477	To determine the tolerability and optimal dose regimen of sGC stimulator, vericiguat in patients with HFpEF.	No significant change in NT-proBNP and LAV was seen in patients receiving vericiguat compared to placebo. Vericiguat was well-tolerated and associated with improved quality of life in patients with HFpEF.
Armstrong et al. [25]	2020	VITALITY-HFpEF study	NCT 03547583	789	To assess the efficacy of vericiguat on the PLS score of KCCQ	24-week treatment with vericiguat at either 15 mg/day or 10 mg/day did not improve the PLS of KCCQ compared to placebo.
Udelson et al. [26]	2020	CAPACITY-HFpEF	NCT 03254485	181	To assess the efficacy and safety of praliciguat on HFpEF patients.	No significant change in peak rate of oxygen consumption, six-minute walk test distance, and ventilator efficiency was seen. Praliciguat was well-tolerated.
Armstrong et al. [27]	2020	VICTORIA	NCT 02861534	5050	To assess the effect of vericiguat on death from cardiovascular causes or HHF in patients with HFrEF.	The composite index of hospitalization for heart failure and death from cardiovascular causes was lower in vericiguat group compared to placebo.