TABLE 8.
Effects of pulmonary hypertension (PH)-specific monotherapy in inoperable chronic thromboembolic PH (CTEPH) patients
| Author (reference), year | Design | Patients | Intervention | Comparator | Significant outcomes |
|---|---|---|---|---|---|
| McLaughlin et al (160),1999 | Case series | n=3, subgroup of CTEPH in study of PH (n=33) | iv epoprostenol for 12 months | None | *Entire group: decreased PVR (−50%) |
| Machherndl et al (167), 2001 | Case series | n=2, subgroup in study of PH (n=12) | inh iloprost 100–150 μg/day × 4–18 months | None | Decreased 6MWD (−189 m); increased PVR (+27%), decreased CI (−10%); no change in WHO FC |
| Olschewski et al (146), 2002 | DB, PC, RCT | n=33, subgroup of CTEPH in study of non-IPAH (n=50) and IPAH (n=51) | inh iloprost 30 μg/day, divided 6–9 doses × 12 weeks | n=24, placebo | *Entire group: OR 3.97 for improved 6MWD >10% and improved WHO FC; “no heterogeneity” between types of PH; non-IPAH group (including CTEPH): overall, no change in 6MWD or WHO FC |
| Bharani et al (145), 2003 | DB, PC, crossover RCT | n=1, subgroup in study of CTEPH (n=10) | Sildenafil 25 mg tid × 2 weeks | Placebo | Decreased echo-RVSP; improved 6MWD, BDI score |
| Ghofrani et al (156), 2003 | Case series | n=12 | Sildenafil 50 mg tid × 6.5 months | None | Improved 6MWD (+54 m); decreased PVRI (−30%), increased CI (+20%) |
| Ono et al (164), 2003 | Retrospective cohort | n=20 | Beraprost 132 μg/day, divided tid-qid × 44–58 months | n=23, conventional therapy | Improved WHO FC in 50%; decreased TPR (−16%) Survival 100%, 85%, 76% versus 87%, 60%, 46% at 1,3,5 years in beraprost versus comparator |
| Ono et al (165), 2003 | Case series | n=8, subgroup in study of n=18 | Beraprost 143 μg/day × 2.3 months | None | *Entire group: Improved WHO FC in 56%, decreased PVR (−17%), decreased BNP levels |
| Scelsi et al (158), 2004 | Case series | n=11, subgroup in study of PH (n=27) | iv epoprostenol × 12 months | None | Improved 6MWD; improved LVED on echo |
| Hoeper et al (150), 2005 | Case series | n=15, subgroup in study of CTEPH (n=19) | Bosentan 125 mg bid × 3 months | None | Entire group: Improved 6MWD (+73 m), decreased PVR (−33%), increased CO (+18%), decreased NT-pro-BNP levels; no change in VO2max, WHO FC |
| Bonderman et al (148), 2005 | Case series | n=14; inoperable, severe comorbidity, or refused PEA | Bosentan 125 mg bid × 6 months | None | Improved 6MWD (+92 m); decreased NT-BNP levels |
| Sharma et al (178), 2005 | Case reports | n=2; not treated with PEA | Bosentan 125 mg bid | None | Improved 6MWD and WHO FC |
| Sheth et al (155), 2005 | Case-series | n=6 | Sildenafil 50 mg tid × 6 weeks | None | Decreased mPAP; no change in PVR, CI and echo parameters; improved WHO FC and MRC dyspnea |
| Hughes et al (147), 2005 | Case series | n=15, subgroup in study of CTEPH (n=20) | Bosentan 125 mg bid × 3 months | None | Improved 6MWD (+45 m); decreased PVR (−28%), increased CO (+21%) |
| Hughes et al (151), 2006 | Case series | n=39, subgroup in study of CTEPH (n=47) | Bosentan 125 mg bid × 12 months | None | Improved 6MWD (+52 m) and WHO FC (24%); decreased TPR (−12%), increased CI (+10%); survival 96%, 86% at 1, 2 years, repectively |
| Andreassen et al (179), 2006 | Case-series | n=19†, subgroup of CTEPH in study of PH (n=61) | Various: inhaled or iv prostanoids, oral ERAs or sildenafil | n=10, age/sex-matched | *Entire group: NT-pro-BNP level independent predictor of mortality on multivariate analysis |
| Kourouklis et al (180), 2006 | Case report | n=1 | Bosentan 125 mg bid × 9 months | None | Decreased RVSP (90 mmHg to 75 mmHg); improved WHO FC (IV to III) |
| Lang et al (163), 2006 | Case series | n=18, subgroup in study of CTEPH (n=23) among PH (n=122) | sc treprostinil 16 84 ng/kg/min × 3–57 months | None | *Entire group: Improved 6MWD (+65 m) and WHO FC (−0.7); survival 89%, 71%, 66% at 1, 3 and 4 years; 10% discontinued |
| Vizza et al (166), 2006 | Case control | n=8 | Beraprost 275 μg/day × 6 months | n=8, IPAH matched for 6MWD | Improved 6MWD (+61 m) versus IPAH (+44 m); improved WHO FC in both groups |
| Cabrol et al (159), 2007 | Case series | n=27 | iv epoprostenol × 3–20 months | None | Improved 6MWD (+66 m) and WHO FC (48%); decreased TPR (−22%), increased CI (+21%); survival 73%, 59%, 41% at 1, 2 and 3 years, respectively |
| Madden et al (153), 2007 | Case series | n=6; “unsuitable for PEA”, subgroup of CTEPH in larger study of PH (n=16) | Sildenafil 50 mg tid × 2–22 months | None | *Entire group: improved 6MWD, CI, PVR at 2 months and LT |
| Reichenberger et al (157), 2007 | Case series | n=104 | Sildenafil 50 mg tid × 3–12 months | None | Improved 6MWD (+51,+56m) at 3,12 months; reduced PVR (−12%) and CI (−14%); no change in WHO FC |
| Seyfarth et al (152), 2007 | Case series | n=10, subgroup in study of CTEPH (n=12) | Bosentan 125 mg bid × ≤24 months | None | *Improved 6MWD and Tei index; improved WHO FC from III to II (n=6); no deaths, no discontinuations at 24 months |
| Ulrich et al (149), 2007 | Case series | n=15; inoperable or refused PEA | Bosentan 125 mg bid × 6 months | None | Improved 6MWD and QOL; improved WHO FC (n=4); decreased mPAP and PVR, increased CI |
| Skoro-Sajer et al (162), 2007 | Case control | n=17, subgroup in study of CTEPH (n=25) | sc treprostinil 21 ng/kg/min ×19 months | n=31 matched, historical cohort | Improved 6MWD (+59 m, +105 m) at 6, 12 months; decreased PVR (−13%) and CI (−14%); survival 80%, 80%, 53% versus 67%, 37%, 16% at 1, 3 and 5 years, repectively, in treprostinil versus comparator |
| Rossi et al (154), 2008 | Case series | n=9 | Sildenafil 25–100 mg tid × 6 months | None | Improved 6MWD, mPAP, PVR, CI and RAP; improved WHO FC |
| Suntharalingam et al (144), 2008 | PC RCT; LT open label, crossover | n=10, subgroup in study of CTEPH (n=19) | Sildenafil 40 mg tid × 3–12 months | RCT: placebo LT open label: none | RCT: decreased PVR (−24%), Improved WHO FC; no change in QOL, 6MWD, CI or NT-pro-BNP levels Open label: improved 6MWD (+36 m), decreased PVR (−21%) and CI (−9%); decreased CAMPHOR symptom/activity and NT-pro-BNP levels (−189) |
| Jaïs et al (141), 2008 | DB, PC, RCT | n=47, subgroup in study of CTEPH (n=77) | Bosentan 125 mg bid × 16 weeks | n=49, placebo | Decreased PVR (−24%); decreased BDI (−0.6 units); no change in CI, 6MWD, WHO FC, TCW; decreased NT-pro-BNP levels (−622) |
Unless otherwise indicated, the number of patients refers specifically to inoperable CTEPH patients.
*
No specific data on treatments or outcomes in CTEPH patients;
†
CTEPH patients not characterized as inoperable versus residual PH postpulmonary endarterectomy (PEA). 6MWD 6 min walk test distance; BDI Borg dyspnea index; bid Twice daily; CAMPHOR Cambridge PH Outcome Review; CI Cardiac index (L/min); CO Cardiac output; DB Double blinded; echo Echocardiography; ERA Endothelin-receptor antagonist; FC Functional class; inh Inhaled; IPAH Idiopathic pulmonary arterial hypertension; iv Intravenous; LT Long term; LVED Left ventricular end diastolic; mPAP Mean pulmonary arterial pressure; MRC Medical Research Council; NT-pro-BNP N-Terminal probrain natriuretic peptide (pg/mL); PC Placebo controlled; PVR Pulmonary vascular resistance; PVRI PVR index; qid Four times daily; QOL Quality of life; RAP Right atrial pressure; RCT Randomized controlled trial; RVSP Right ventricular systolic pressure; sc Subcutaneous; TCW Time to clinical worsening; tid Three times daily; TPR Total peripheral resistance; VO2max Maximal oxygen uptake