Table 3.
Pivotal Trials for the Medications Used in SSc-PAH with Comparison of the Treatment Response Between SSc-PAH and IPAH
| Trial Name/Author | Medication | Analysis Group | Primary Endpoint | Secondary Endpoint | PAH-CTD vs IPAH Response |
|---|---|---|---|---|---|
| SUPER164,65 | Sildenafil | PAH including CTD | 6MWT | WHO FC Hemodynamics |
Similar results |
| PHIRST-166,67 | Tadalafil | PAH including CTD | 6MWT | WHO FC Clinical worsening Quality of life |
PAH-CTD patients had reduced improvement in regard to all end points |
| PATENT-168,69 | Riociguat | PAH including CTD | 6MWT | WHO FC NT-proBNP Hemodynamics Time to clinical worsening Borg dyspnea scale Quality of life |
Improvements were less pronounced in PAH-CTD patients. However, 2-year survival rates were similar |
| BREATHE-174 | Bosentan | PAH including CTD | 6MWT | WHO FC Borg dyspnea index Time to clinical worsening |
Improvements were less pronounced in SSc-PAH than in IPAH (46m vs 3m regarding 6MWD) |
| ARIES-175,76 | Ambrisentan | PAH including CTD | 6MWT | WHO FC Borg dyspnea score NT-proBNP Clinical worsening |
Time to clinical worsening was similar. Improved survival in both groups though more pronounced in IPAH |
| SERAPHIN77 | Macitentan | PAH including CTD | Worsening of PAH or death | 6MWD WHO FC Death due to PAH Hospitalization due to PAH Death from any cause |
Reduced morbidity without difference between CTD-PAH and IPAH according to a meta-analysis78 |
| Badesch DB et al82 | Epoprostenol | SSc-PAH | 6MWT | Hemodynamics Survival |
Not applicable |
| Simonneau G. et al87,88 | Treprostinil | PAH including CTD-PAH | 6MWT | Borg Dyspneal Scale Hemodynamics Quality of life |
Improvements were achieved in both groups though less pronounced in CTD-PAH |
| Caravita S et al89 | Iloprost | CTD-PAH | 6MWT | Hemodynamics NT-proBNP |
Not applicable |
| GRIPHON90,91 | Selexipag | PAH including CTD-PAH | Composite death from any cause and any complication from PAH | 6MWD All-cause mortality |
Primary endpoint was consistent to IPAH 6MWD improved in IPAH while it minimally progressed in CTD |
Abbreviations: 6MWD, six-minute walk distance; distance; 6MWT, six-minute walk test; CTD, connective tissue disease; IPAH, idiopathic pulmonary arterial hypertension; PAH, pulmonary arterial hypertension; WHO FC, world health organization functional class; NT-proBNP, N-terminal-pro brain natriuretic peptide.