Table 1.

Completed Longitudinal Randomized-Controlled Trials of Pulmonary Vasodilators in Patients with Heart Failure

Study (Year)	Author	Drug	Inclusion	PH (%)	Subjects	Study Duration	Primary Outcome	Results
FIRST (1996)50	Califf, et al.	epoprostenol	HFrEF, NYHA IIIB/IV	NR	n=471	>36 weeks	Survival	Early termination for decreased survival
HEAT (2002)54	Luscher, et al.	darusentan	HFrEF, NYHA III	NR	n=179	3 weeks	Hemodynamics (CO, PCWP)	Increased cardiac output, no change in PAP
EARTH (2004)55	Anand, et al.	darusentan	HFrEF, NYHA IIIB/IV	NR	n=642	24 weeks	Change in LVESV (MRI)	No benefit
ENABLE (2002)56	Kalra, et al.	bosentan (low-dose)*	HFrEF, NYHA IIIB/IV	NR	n=1613	18 months	Mortality, Hospitalization	No benefit, increased early HF
REACH-1 (2005)57	Packer, et al.	bosentan (high-dose)**	HFrEF, NYHA III/IV	NR	n=174	26 weeks	Change in clinical state	Early termination for fluid retention, elevated LFTs
Guazzi (2007)58	Guazzi, et al.	sildenafil	HFrEF, NYHA II/III	NR	n=46	24 weeks	Peak VO2	Improved exercise performance, breathlessness
Guazzi (2011)59	Guazzi, et al.	sildenafil	PH due to HFpEF	100%	n=44	12 months	PA pressure/RV function	Improved PAP, RV function
RELAX (2013)60	Redfield, et al.	sildenafil	HFpEF, NYHA II-IV	53%	n=216	24 weeks	Change in peak O2 consumption	No benefit
LEPHT (2013)61	Bonderman, et al.	riociguat	PH due to HFrEF	100%	n=201	16 weeks	Change in mPAP	No change in PAP, decrease in PVR, increase CI

Data taken from Fang et al, JHLT (2012)³².

Ongoing Trials – Sil-HF HFrEF/PH, BID=twice daily, CI=cardiac index, CO=cardiac output, HF=heart failure, HFpEF=heart failure with preserved ejection fraction, HFrEF=heart failure with reduced ejection fraction, LFTs=liver function tests, LHD=left heart disease, LVESV=left ventricular end systolic volume, NR=not reported, NYHA=New York Heart Association functional class, PAP=pulmonary artery pressure, PCWP=pulmonary capillary wedge pressure, PH=pulmonary hypertension, RV=right ventricle

125 mg BID

^**500 mg BID