Table 2.

Summary of phase 2 and 3 clinical trials of cGMP modulating drugs in Heart Failure with Reduced Ejection Fraction (HFrEF) and Heart Failure with Preserved Ejection Fraction (HFpEF).

Drug	cGMP Pathway Effect	Primary Endpoint	Duration (months)	Improvement in Primary Endpoint?
HFrEF:
Nesiritide	Direct GC-A activator	Time to all-cause death or cardiovascular or renal hospitalization	3	No
Vericiguat	Direct soluble GC stimulator	Change from baseline to week 12 in log-transformed N-terminal pro-B-type NP	3	No
Sacubitril/ Valsartan	Sacubitril: Inhibitor of Neprilysin	Composite of cardiovascular death or hospitalization for heart failure	27 (median)	Yes
Isosorbide Dinitrate and Hydralazine	NO donor	Mortality	24	Yes
Isosorbide Dinitrate and Hydralazine	NO donor	Composite of death first HF hospitalization, and change in the quality of life at 6 months (self-described black patients)	18	Yes
HFpEF
Vericiguat	Direct soluble GC stimulator	1. Change from baseline in log-transformed N-terminal pro-B-type natriuretic peptide 2. Left atrial volume	3	No
Sildenafil	PDE5 inhibitor	Change in peak oxygen consumption after 24 weeks of drug	6 (3 month low dose, then 3 month high dose)	No
Isosorbide Mononitrate	NO donor	Daily activity level (measured by accelerometer)	1.5	No
Sacubitril/ Valsartan	Sacubitril: Inhibitor of Neprilysin	Change in NTproBNP from baseline to 12 weeks	9	Yes