Table 2.

Selected randomized controlled trials using PH-directed medical therapy in CTEPH

Study	Medication	N, design; evaluation interval	6MWD change, meters	mPAP change, mmHg	PVR change, dynes/sec/cm5	CO change, L/min	NT-proBNP change, pg/mL	WHO FC change	Borg dyspnea score change
Ghofrani (2013) (CHEST-1)	Riociguat vs placebo in CTEPH	N=261, RCT; week 12	39 vs −6	−4 vs 0.8	-226 vs 23	0.8 vs −0.03	−291 vs 76	33% vs 15% improved	−0.8 vs 0.2
Simonneau (2015) (CHEST-2)	Riociguat vs placebo in CTEPH	N=211, 1 year follow-up of CHEST-1	59 vs 37	Not reported	Not reported	Not reported	−375 vs −505	50% vs 39% improved	−0.8 vs −0.57
Jais (2008) (BENEFiT)	Bosentan vs placebo in CTEPH	N=157, RCT; week 16	2.9 vs 0.8	Placebo corrected −2.5*	−146 vs +30	Placebo corrected CI +0.3	Treatment effect −622 ng/L in favor of bosentan	14.5% vs 11.3% improved*	−0.4 vs 0.2
Ghofrani (2017) (MERIT-1)	Macitentan vs placebo in CTEPH	N=80, RCT, week 16 (hemodynamics) and week 24 (NT-proBNP, 6MWD)	35 vs 1	−3.5 vs −1.7	−206 vs −86	0.76 vs −0.02	−651 vs −360	0% worsened vs 8% worsened*	−0.1 vs −.3*
Escribano-Subias (2018) (AMBER-1)	Ambrisentan vs placebo in CTEPH	N=33, RCT; week 16	28.3 vs 6.8	Not reported	−212.5 vs −108.5	Not reported	Geometric mean −29.4% of baseline vs +14.1% of baseline	Not reported	Not reported
Suntharalingam (2008)	Sildenafil vs placebo in CTEPH	N=19, RCT; week 12	17.9 vs 0.4*	−5.8 vs 0.4*	−179 vs 18	CI −0.1 vs −0.1*	−355 vs −77*	100% vs 0% improved	−0.7 vs 0.2*
Sadushi-Kolici (2019)	High-dose vs low-dose subcutaneous treprostinil	N=105, RCT; week 24	45.4 vs 3.8	−3.4 vs −0.4	−214 vs 73	0.6 vs −0.2	−157.5 vs 330.6	51% vs 17% improved	−0.4 vs −0.1*