TABLE 1.
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] | |||||
Bosentan | Placebo | Sildenafil | Placebo | Riociguat | Placebo | Prior riociguat | Prior placebo | |
Patients n | 77 | 80 | 9 | 10 | 173 | 88 | 155 | 82 |
Study design | Multicentre, randomised, double-blind, placebo-controlled | Randomised, double-blind, placebo-controlled | Multicentre, randomised, double-blind, placebo-controlled | Long-term, open-label extension | ||||
Primary end-point | Change in PVR and 6MWD after 16 weeks | Change in 6MWD after 12 weeks | Change in 6MWD after 16 weeks | None | ||||
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 |
WHO FC % | ||||||||
Improved | 14 | 11 | 44 | 0 | 33 | 15 | 50 | 39 |
No change | 83 | 80 | 56 | 80 | 62 | 78 | 45 | 59 |
Worsened | 3 | 9 | 0 | 20 | 5 | 7 | 4 | 2 |
Clinical worsening events % | 4 | 6 | 2 | 6 | 16 | |||
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 | ||||||
CAMPHOR score | ||||||||
Symptoms | −2±5# | −0±3# | ||||||
Activity | −3±2# | −1±3# | ||||||
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.