Table. 1—

Summary of combination therapy studies in pulmonary arterial hypertension(PAH) involving small numbers of patients and case reports

Combination by background therapyPatients nStudy durationAetiology of PAHKey findings: combination versus baseline therapy alone/placeboRef.
    Epoprostenol + iloprost8Single doseIPAHSignificant improvements in mean Ppa, CI, Sv,O2, and Pa,O2[23]
    Beraprost + iloprost2312 monthsPAH-CHDImprovement in 6MWD and RVSP[24]
    Beraprost/iloprost + bosentan2016 monthsIPAHImprovement in 6MWD[25]
1613.5 monthsIPAH, thromboembolicSignificant improvement in 6MWD and Tei index[26]
    Epoprostenol + bosentan81 yrIPAHReduction in epoprostenol dose and side-effectsDiscontinuation of epoprostenol and stabilisation of haemodynamics for ≤1 yr in three patients[27]
81 yrIPAHSignificant decrease in mean PpaDelay in disease progression[28]
    Iloprost + bosentan912 weeksNot givenSignificant improvement in exercise capacity[29]
    Treprostinil + bosentan19∼3 yrsNot givenSignificant additional improvement in Ppa, 6MWD and Borg dyspnoea scale[30]
    Epoprostenol + sildenafil53 monthsIPAHImprovement in mean Pra and WHO functional class[31]
35 monthsIPAH, PAH-CHDReduced mean Ppa and PVRIncreased 6MWD[32]
32 hIPAHSignificant decrease in mean Ppa and PVR[33]
    Iloprost + sildenafil303 hIPAH, CTEPHIncreased vasodilation[34]
149–12 monthsPAH unresponsive to iloprostImproved 6MWD, haemodynamics and WHO functional class[35]
    Prostanoids + sildenafil202 yrsNot givenSignificant improvement in WHO functional class and signs of right heart failureIncrease in 6MWD after 1- and 2-yr follow-up[36]
4Not givenIPAH, PAH-CTDImprovements in 6MWD, Ppa and dyspnoea[37]
Bosentan + sildenafil912 monthsIPAHImprovements in 6MWD and CPET[38]
3≤24 monthsIPAHImprovement in functional capacity, BNP[39]
111.1 yrsIPAH, PAH-CTDImprovement in WHO functional class, 6MWD and mean Ppa[40]
253 monthsIPAH, PAH-SScImproved WHO functional class and 6MWD in IPAH but not in PAH-SSc[41]
106 monthsIPAH, PAH-CTDIncrease in 6MWD[42]
Bosentan + prostanoids353 monthsIPAHImprovements in 6MWD, CI, mean Ppa and WHO functional class[43]
Bosentan + iloprost4012 weeksIPAHNo effect on 6MWD[44]
6712 weeksIPAH, APAHSignificant increase in 6MWD and WHO functional classDelay in time to clinical worseningImprovements in mean Ppa and PVR[16]
Sildenafil + beraprost11 monthPAH-SScDecrease in Ppa and PVRImprovements in 6MWD and WHO functional class[45]
  • IPAH: idiopathic PAH; Ppa: pulmonary arterial pressure; CI: cardiac index; Sv,O2: mixed venous oxygen saturation; Pa,O2: arterial oxygen tension; CHD: congenital heart disease; 6MWD: 6-min walk distance; RVSP: right ventricular systolic pressure; Pra: right arterial pressure; WHO: World Health Organization; PVR: pulmonary vascular resistance; CTEPH: chronic thromboembolic pulmonary hypertension; CTD: connective tissue disease; CPET: cardiopulmonary exercise testing; BNP: brain natriuretic peptide; SSc: systemic sclerosis; APAH: associated PAH.