Table 1.

Representative efficacy studies of early (WHO FC I–II) intervention and relevant combination therapy studies for PAH

RCT	PAH drug(s)	Patients in WHO FC I–II, %	Outcome
EARLY2	Bosentan	100	Primary endpoint of combined 6MWD plus PVR not achieved; PVR decreased >20%
SERAPHINa,6	Macitentan	52	Significant decrease (50%) in primary endpoint of clinical events, primarily because of decreased hospitalization for PAH. 66% of patients on background therapy
GRIPHONa,7	Selexipag	47	Significant decrease (40%) in primary endpoint of clinical events, primarily because of less disease progression and hospitalization. 80% of patients on background therapy
PATENT-1a,18	Riociguat	45	Significant improvement in 6MWD as primary endpoint. 50% of patients on background therapy
AMBITION3	Ambrisentan-tadalafil combination	31	Initial combination therapy with ambrisentan and tadalafil significantly decreased (50%) clinical events as primary endpoint. Hospitalization in combination group one-third of that with monotherapy
COMPASS-24	Bosentan added to PDE5i	42	No benefit in primary endpoint of clinical events from adding bosentan to PDE5i, usually sildenafil. Study lasted 7 years with 20% of patients missing information

Notes:

^aBackground therapy permitted.

Abbreviations: 6MWD, 6-minute walk distance; PAH, pulmonary artery hypertension; PDE5i, phosphodiesterase-5 inhibitor; PVR, pulmonary vascular resistance; RCT, randomized controlled trial; WHO FC, World Health Organization functional class.