TABLE 1

Baseline characteristics of included studies

First author, year [reference]ParticipantsPAH subgroupMean age yearsFollow-up durationWHO functional classInterventional group treatment (upfront therapy)Control group treatmentOutcome measuresAdverse events
Badagliacca,# 2018 [6]165IPAH54155±65 days3.2±0.4Group 1: prostanoids+ERAs or PDE5i
Group 2: ERAs+PDE5i
Group 3: ERAs or PDE5i
Group 4: prostanoids
PVR, mPAP, CI, RAP, 6MWDNR
Badagliacca, 2021 [7]181IPAH, CTD-PAH, CHD-PAH with closed shunt53180 (144–363) daysI–II: 37 (20.4)
III: 127 (70.2)
IV: 17 (9.4)
Ambrisentan-tadalafil or ambrisentan-sildenafil or bosentan-tadalafil or bosentan-sildenafil or macitentan-tadalafil or macitentan-sildenafilNAPVR, mPAP, CI, RAP, 6MWDNR
Chin, 2021 [8]247PAH51.926 weeksI–II: 50 (20.2)
III–IV: 197 (79.8)
Macitentan-tadalafil-selexipagMacitentan-tadalafil-placeboPVR, mPAP, CI, RAP, SvO2, NT-proBNP, 6MWDHeadache, diarrhoea, nausea, pain in extremity, jaw pain, vomiting
D'Alto, 2020 [9]21IPAH4424±14 monthsIII: 12 (57)
IV: 9 (43)
Ambrisentan-tadalafil-treprostinilBosentan or ambrisentan or sildenafil or tadalafil;PVR, mPAP, CI, RAP, SvO2, NT-proBNP, 6MWDPeripheral oedema, nasal congestion, flushing
Hassoun, 2015 [10]24SSc-PAH59.936 weeksII: 8 (35)
III: 15 (65)
Ambrisentan-tadalafilNAPVR, mPAP, CI, RAP, NT-proBNP, 6MWDPeripheral oedema, nasal congestion, dyspnoea, cough, headache, dizziness, fatigue, abdominal pain, nausea-vomiting, hypotension, diarrhoea
Kemp, 2012 [11]23IPAH, HPAH, DPAH434±1 monthsIII: 16 (70)
IV: 7 (30)
Epoprostenol-bosentanEpoprostenol monotherapyPVR, mPAP, CI, RAP, SvO2, 6MWDJaw pain, facial flushing, headache, gastrointestinal disturbance, leg pain, catheter infections, increase in liver enzymes
Rinaldi, 2018 [12]19PAHNRNRII–III: 100Ambrisentan-tadalafilBosentan or sildenafil monotherapy or other ERAs or PDE5i monotherapy or bosentan-sildenafil or macitentan-sildenafilPVR, mPAP, CI, RAP, SvO2, 6MWD
Sitbon, 2014 [13]19IPAH, HPAH, DPAH39.44 monthsIII: 8 (42)
IV: 11 (58)
Bosentan-sildenafil-epoprostenolNAPVR, mPAP, CI, RAP, SvO2, 6MWDJaw pain, headache, diarrhoea, flushing, increase in liver enzymes
Sitbon, 2016 [14]97PAH54.14.1 (3.5–4.9) monthsII: 15 (15)
III: 70 (72)
IV: 12 (12)
Bosentan-sildenafil or bosentan-tadalafil or ambrisentan-sildenafil or ambrisentan-tadalafilNAPVR, mPAP, CI, RAP, SvO2, BNP, 6MWDPeripheral oedema, increase in liver enzymes, blurred vision
Sitbon, 2020 [15]46PAH57.416 weeksII: 10 (21.7)
III: 36 (78.3)
Macitentan-tadalafilNAPVR, mPAP, CI, RAP, SvO2, NT-proBNP, 6MWDPeripheral oedema, headache, diarrhoea, dyspnoea, anaemia, asthenia, fatigue, increase in liver enzymes
Sulica, 2019 [16]15PAH55.813.7±3.6 monthsIII: 93
IV: 7
Macitentan-riociguatNAPVR, mPAP, CI, RAP, SvO2, BNP, 6MWDPeripheral oedema, nasal congestion, headache, hypotension
van de Veerdonk, 2017 [17]80IPAH, HPAH, DPAH4912 monthsII: 24 (30)
III: 56 (70)
Bosentan-sildenafil or bosentan-tadalafil or ambrisentan-sildenafil or ambrisentan-tadalafilBosentan or ambrisentan or macitentan or sitaxentanor or sildenafil or tadalafilPVR, mPAP, CI, RAP, SvO2, NT-proBNP, 6MWDIncrease in liver enzymes
Zhang, 2014 [18]68CHD-PAHNR6 monthsNRUpfront iloprost-tadalafilSequential iloprost-tadalafilPVR, SvO2, 6MWD

Data are presented as n, mean±sd, median (interquartile range) or n (%). PAH: pulmonary arterial hypertension; WHO: World Health Organization; IPAH: idiopathic pulmonary arterial hypertension; ERA: endothelin receptor antagonist; PDE5i: phosphodiesterase type 5 inhibitor; PVR: pulmonary vascular resistance; mPAP: mean pulmonary arterial pressure; CI: cardiac index; RAP: right atrial pressure; 6MWD: 6-min walk distance; NR: not reported; CTD: connective tissue disorder; CHD: congenital heart disease; NA: not applicable; SvO2: mixed venous oxygen saturation; NT-proBNP: N-terminal pro-brain natriuretic peptide; SSc: systemic sclerosis; HPAH: heritable pulmonary arterial hypertension; DPAH: drug-induced pulmonary arterial hypertension. #: in this study, group 1 was treated with treprostinil-tadalafil or treprostinil-ambrisentan or treprostinil-bosentan or epoprostenol-tadalafil or epoprostenol-bosentan or iloprost-ambrisentan; group 2 was treated with ambrisentan-tadalafil or ambrisentan-sildenafil or bosentan-tadalafil or bosentan-sildenafil or macitentan-tadalafil or macitentan-sildenafil; group 3 was treated with bosentan or ambrisentan or sildenafil or tadalafil; group 4 was treated with treprostinil or epoprostenol.