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).