Efficacy data for randomised controlled trials of targeted therapy in patients with chronic thromboembolic pulmonary hypertension

BENEFIT [39]Sildenafil study [41]CHEST-1 [38]CHEST-2 [40]
BosentanPlaceboSildenafilPlaceboRiociguatPlaceboPrior riociguatPrior placebo
Patients n77809101738815582
Study designMulticentre, randomised, double-blind, placebo-controlledRandomised, double-blind, placebo-controlledMulticentre, randomised, double-blind, placebo-controlledLong-term, open-label extension
Primary end-pointChange in PVR and 6MWD after 16 weeksChange in 6MWD after 12 weeksChange in 6MWD after 16 weeksNone
6MWD m+3 (−13–19)+1 (−18–20)+18±34#+0±49#+39±79***−6±84+591±589+37±69
PVR dyn·s·cm−5−146+ (−207–−85)+30 (−25–85)−179 (245)*+18 (76)−226±248***+23±274
mPAP mmHg−6±7#+0±6#−4±7***+1±7
TPR dyn·s·cm−5+
PAOP mmHg+0±3#−0±3#
mRAP mmHg−0±5#−1±6#−1±5−1±5
PCWP mmHg+1±4+0±4
mPa mmHg−9±12***−0±12
Cardiac output L·min−1+1±1***−0±1
Cardiac index L·min−1·m−2***−0±1#−0±0#
SvO2 %
SaO2 %−2±4−3±8
PaO2 mmHg−3±15−5±12
Heart rate beats·min−1+2±12+1±12
NT-proBNP pg·mL−1−200**,+400−355±648#−77±130#−291±1717***+76±1447−375±1182−505±1591
 No change8380568062784559
Clinical worsening events %462616
Borg dyspnoea score−0 (−1–0)*+0 (−0–1)−1±1#+0±2#−1±2**+0±2−1±2−1±2
EQ-5D score+0.06±0.28−0.08±0.34+0.12±0.29+0.01±0.30
LPH score−7±19−2±19
 Quality of life−2±7#−0±4#
  • Data are presented as mean±sd or mean (95% CI), unless otherwise stated. Data represent change from baseline at 16 weeks (CHEST-1 and BENEFIT), 12 weeks (sildenafil study) or 1 year (CHEST-2). 6MWD: 6-min walking distance; PVR: pulmonary vascular resistance; mPAP: mean pulmonary arterial pressure; TPR: total pulmonary resistance; PAOP: pulmonary artery occlusion pressure; mRAP: mean right atrial pressure; PCWP: pulmonary capillary wedge pressure; mPa: mean arterial pressure; SvO2: mixed venous oxygen saturation; SaO2: arterial oxygen saturation; PaO2: arterial oxygen tension; NT-proBNP: N-terminal of the pro-brain natriuretic peptide; WHO FC: World Health Organization functional class; EQ-5D: EuroQoL 5-dimensions quality-of-life questionnaire; LPH: Living with Pulmonary Hypertension questionnaire; CAMPHOR: Cambridge Pulmonary Hypertension Outcome Review. #: mean±se; : estimated from graph. *: p<0.05; **: p<0.01; ***: p<0.001; +: p<0.0001 versus placebo.