Findings from smaller clinical studies of pharmacological therapies in patients with chronic thromboembolic pulmonary hypertension (CTEPH)

AgentFirst author [ref.]YearStudy typeDurationPatientsMean±sd age yearsOutcomes versus baseline
Bosentan (oral)Hoeper [48]2005Open-label3 monthsInoperable CTEPH (n=19)60±8Increase in 6MWD (p=0.009); decrease in PVR (p<0.001); no change in WHO-FC
Bonderman [49]2005Open-label6 monthsInoperable CTEPH (n=16)70±3Increase in 6MWD (p=0.01); decrease in NT-proBNP (p=0.01); NYHA-FC improved for 69% of patients
Hughes [50]2006Retrospective12 monthsInoperable 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]2007Open-label24 monthsInoperable and persistent CTEPH (n=12)57±15Increase 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]2009Retrospective>24 monthsInoperable CTEPH (n=18)63±14Increase 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]2014Retrospective>24 monthsInoperable CTEPH (n=7)63±7No 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]2004Retrospective12 monthsInoperable 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]2007RetrospectiveMean 20 monthsInoperable CTEPH (n=27)51±13Decrease 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]2002RCT versus placebo12 weeksPAH 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]2003Retrospective, beraprost+CT versus CT aloneMean 36 monthsInoperable 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]2006Retrospective36 monthsPAH (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]2007Open-label versus historical controlMean 24 monthsInoperable 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]2003Open-label6 monthsInoperable CTEPH (n=12)NAIncrease in 6MWD (p=0.02); decrease in PVR (p=0.004)
Reichenberger [61]2007Open-label12 monthsInoperable CTEPH (n=104)62±11Increase 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]2008RCT versus placebo12 weeksInoperable 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 extension12 monthsInoperable CTEPH (n=17)NAIncrease in 6MWD (p=0.014); decrease in PVR (p=0.001) and NT-proBNP (p=0.004)
Riociguat (oral)Ghofrani [26]2013RCT versus placebo16 weeksInoperable 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 drugsNishimura [63]2013Retrospective, single-centre cohort; group 1 diagnosed 1986–1998, group 2 diagnosed 1999–2004, group 3 diagnosed 2005–2010Inoperable CTEPH (n=95)55±14Significantly 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).