Figures
- FIGURE 1
Mean change from baseline in 6-min walking distance (6MWD) in the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial (CHEST)-1 and CHEST-2 studies. Data are observed values; error bars represent sem. Reproduced from [44] with permission from the publisher.
- FIGURE 2
Kaplan–Meier plots for a) clinical worsening and b) survival in the overall population during the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial (CHEST)-2 study. At 1 year, the estimated rate of clinical worsening-free survival was 88% and the estimated rate of survival was 97%. Reproduced from [44] with permission from the publisher.
Tables
- TABLE 1
Change from baseline in primary and selected secondary end-points with riociguat and placebo in the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial (CHEST)-1 study
End-point Placebo Riociguat p-value# Patients Baseline Change Patients Baseline Change Primary end-point 6MWD m 88 356±75 –6±84 173 342±82 39±79 <0.001 Selected secondary end-points PVR dyn·s·cm–5 82 779±401 23±274 151 791±432 –226±248 <0.001 NT-proBNP pg·mL−1 73 1706±2567 76±1447 150 1508±2338 –291±1717 <0.001 WHO-FC 87 Class I: 0 Class II: 25 (29%) Class III: 60 (69%) Class IV: 2 (2%) 13 (15%) moved to lower class; 68 (78%) stayed the same; 6 (7%) moved to higher class 173 Class I: 3 (2%) Class II: 55 (32%) Class III: 107 (62%) Class IV: 8 (5%) 57 (33%) moved to lower class; 107 (62%) stayed the same; 9 (5%) moved to higher class 0.003 -
Data are presented as n or mean±sd, unless otherwise stated. 6MWD: 6-min walking distance; PVR: pulmonary vascular resistance; NT-proBNP: N-terminal pro-brain natriuretic peptide; WHO-FC: World Health Organization functional class. #: calculated with the use of stratified Wilcoxon test for the change from baseline to last visit. Reproduced and modified from [26] with permission from the publisher.
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- TABLE 2
Change from baseline in primary and selected secondary end-points with bosentan and placebo in the Bosentan Effects in Inoperable Forms of Chronic Thromboembolic Pulmonary Hypertension (BENEFiT) study
End-point Placebo Bosentan p-value# Patients Baseline Change Patients Baseline Change Co-primary end-points 6MWD m 73 344.5 (325.2–363.8) 0.8 (–18.1–19.7) 67 340.0 (319.2–360.8) 2.9 (–12.9–18.8) 0.5449 PVR dyn·s·cm–5 71 787 (708–866) 30 (–25–85) 66 778 (698–857) –146 (–207– –85) <0.0001 Selected secondary end-points NT-proBNP ng·L−1 76 1405 72 1481 –622 (–1018– –225)¶ 0.0034 WHO-FC II/III/IV 80 22/56/2 11.3% moved to lower class; 8.8% moved to higher class 76 22/51/3 14.5% moved to lower class; 2.6% moved to higher class ns -
Data are presented as n or mean (95% confidence interval), unless otherwise stated. 6MWD: 6-min walking distance; PVR: pulmonary vascular resistance; NT-proBNP: N-terminal pro-brain natriuretic peptide; WHO-FC: World Health Organization functional class; ns: nonsignificant. #: calculated with the use of stratified Wilcoxon test for the change from baseline and the Wilcoxon rank sum test for treatment effect; ¶: data for treatment effect, not change from baseline. Data from [41].
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- TABLE 3
Findings from smaller clinical studies of pharmacological therapies in patients with chronic thromboembolic pulmonary hypertension (CTEPH)
Agent First author [ref.] Year Study type Duration Patients Mean±sd age years Outcomes versus baseline Bosentan (oral) Hoeper [48] 2005 Open-label 3 months Inoperable CTEPH (n=19) 60±8 Increase in 6MWD (p=0.009); decrease in PVR (p<0.001); no change in WHO-FC Bonderman [49] 2005 Open-label 6 months Inoperable CTEPH (n=16) 70±3 Increase in 6MWD (p=0.01); decrease in NT-proBNP (p=0.01); NYHA-FC improved for 69% of patients Hughes [50] 2006 Retrospective 12 months Inoperable and persistent CTEPH (n=47) 60 (27–82)# Increase in 6MWD (p<0.001); no change in PVR (p=0.171); WHO-FC improved for 24% of patients Seyfarth [51] 2007 Open-label 24 months Inoperable and persistent CTEPH (n=12) 57±15 Increase in 6MWD (p<0.005) at 6 months, maintained over 24 months; decrease in Tei index (p<0.005) at 6 months, maintained over 24 months; WHO-FC improved for 50% of patients over 18 months Post [52] 2009 Retrospective >24 months Inoperable CTEPH (n=18) 63±14 Increase in 6MWD (p=0.01) at 12–24 months but this decreased with longer treatment; nonsignificant decrease in NT-proBNP (p=0.31) at 12–24 months that increased with longer treatment; NYHA-FC improved (p=0.03) with long-term treatment (>24 months) Nishikawa-Takahashi [53] 2014 Retrospective >24 months Inoperable CTEPH (n=7) 63±7 No change in 6MWD (p=0.11); decrease in PVR (p<0.05) and NT-proBNP (p<0.05); WHO-FC improved in all patients (p=0.005) Epoprostenol (i.v.) Scelsi [54] 2004 Retrospective 12 months Inoperable CTEPH (n=11) 50±11 (CTEPH only) Increase in exercise tolerance (p=0.0006); increase in clinical status; NYHA-FC improvement (p=0.0001) Cabrol [55] 2007 Retrospective Mean 20 months Inoperable CTEPH (n=27) 51±13 Decrease in mPAP (p=0.001) and TPR (p<0.0001) at 3 months, maintained over 20 months; NYHA-FC improved for 48% of patients (p<0.0001) at 3 months and for 50% at 20 months; sustained improvement in 6MWD (p=0.03) at 20 months Iloprost (inhaled) Olschewski [56] 2002 RCT versus placebo 12 weeks PAH and CTEPH (101 iloprost, 102 placebo) 51±13 (iloprost) 53±12 (placebo) Increase in 6MWD (p=0.004); no difference in haemodynamics between iloprost and placebo; NYHA-FC improvement (p=0.03) Beraprost (oral) Ono [57] 2003 Retrospective, beraprost+CT versus CT alone Mean 36 months Inoperable CTEPH (20 beraprost+CT, 23 CT) 56±10 (beraprost) 52±14 (CT) Decrease in TPR (p<0.05) at 2 months with beraprost; NYHA-FC improved for 50% of patients at 2 months with beraprost; improved 1-, 3- and 5-year survival rates with beraprost (100%, 85% and 76%, respectively) versus CT alone (87%, 60% and 46%, respectively) Treprostinil (subcutaneous) Lang [58] 2006 Retrospective 36 months PAH (n=99) and CTEPH (n=23) 49 (12–81)# Increase in 6MWD (p=0.0001); NYHA-FC improvement (p=0.0001); results consistent across all types of PH Skoro-Sajer [59] 2007 Open-label versus historical control Mean 24 months Inoperable CTEPH (n=25) 59±13 (treprostinil) 62±15 (control) Increase in 6MWD (p=0.01); decrease in PVR (p=0.01) and NT-proBNP (p=0.02); WHO-FC improvement (p=0.001) Sildenafil (oral) Ghofrani [60] 2003 Open-label 6 months Inoperable CTEPH (n=12) NA Increase in 6MWD (p=0.02); decrease in PVR (p=0.004) Reichenberger [61] 2007 Open-label 12 months Inoperable CTEPH (n=104) 62±11 Increase in 6MWD at 3 months (p=0.0001) and 12 months (p=0.0005); decrease in PVR at 3 months (p=0.0002); WHO-FC improvement at 3 months (p=0.01) and 12 months (p=0.001) Suntharalingam [62] 2008 RCT versus placebo 12 weeks Inoperable CTEPH (9 sildenafil, 10 placebo) 50±13 (sildenafil) 60±14 (placebo) No difference in 6MWD between two groups; decrease in PVR (p=0.044); WHO-FC improvement (p=0.025) Open-label extension 12 months Inoperable CTEPH (n=17) NA Increase in 6MWD (p=0.014); decrease in PVR (p=0.001) and NT-proBNP (p=0.004) Riociguat (oral) Ghofrani [26] 2013 RCT versus placebo 16 weeks Inoperable and persistent CTEPH (173 riociguat, 88 placebo) 59±14 (riociguat) 59±13 (placebo) Increase in 6MWD (p<0.001); decrease in PVR (p<0.001) and NT-proBNP (p<0.001); WHO-FC improvement (p=0.003) “Modern treatment”: bosentan, sildenafil, clinical trial drugs Nishimura [63] 2013 Retrospective, single-centre cohort; group 1 diagnosed 1986–1998, group 2 diagnosed 1999–2004, group 3 diagnosed 2005–2010 Inoperable CTEPH (n=95) 55±14 Significantly improved survival in group 3 compared with groups 1 and 2 -
6MWD: 6-min walking distance; PVR: pulmonary vascular resistance; WHO-FC: World Health Organization functional class; NT-proBNP: N-terminal pro-brain natriuretic peptide; NYHA-FC: New York Heart Association functional class; mPAP: mean pulmonary artery pressure; TPR: total pulmonary resistance; RCT: randomised controlled trial; PAH: pulmonary arterial hypertension; CT: conventional therapy; PH: pulmonary hypertension; NA: not available. #: data presented as mean (range).
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Disclosures
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