Summary of combination therapy studies in pulmonary arterial hypertension(PAH) involving small numbers of patients and case reports
Combination by background therapy | Patients n | Study duration | Aetiology of PAH | Key findings: combination versus baseline therapy alone/placebo | Ref. |
Prostanoids | |||||
Epoprostenol + iloprost | 8 | Single dose | IPAH | Significant improvements in mean Ppa, CI, Sv,O2, and Pa,O2 | [23] |
Beraprost + iloprost | 23 | 12 months | PAH-CHD | Improvement in 6MWD and RVSP | [24] |
Beraprost/iloprost + bosentan | 20 | 16 months | IPAH | Improvement in 6MWD | [25] |
16 | 13.5 months | IPAH, thromboembolic | Significant improvement in 6MWD and Tei index | [26] | |
Epoprostenol + bosentan | 8 | 1 yr | IPAH | Reduction in epoprostenol dose and side-effectsDiscontinuation of epoprostenol and stabilisation of haemodynamics for ≤1 yr in three patients | [27] |
8 | 1 yr | IPAH | Significant decrease in mean PpaDelay in disease progression | [28] | |
Iloprost + bosentan | 9 | 12 weeks | Not given | Significant improvement in exercise capacity | [29] |
Treprostinil + bosentan | 19 | ∼3 yrs | Not given | Significant additional improvement in Ppa, 6MWD and Borg dyspnoea scale | [30] |
Epoprostenol + sildenafil | 5 | 3 months | IPAH | Improvement in mean Pra and WHO functional class | [31] |
3 | 5 months | IPAH, PAH-CHD | Reduced mean Ppa and PVRIncreased 6MWD | [32] | |
3 | 2 h | IPAH | Significant decrease in mean Ppa and PVR | [33] | |
Iloprost + sildenafil | 30 | 3 h | IPAH, CTEPH | Increased vasodilation | [34] |
14 | 9–12 months | PAH unresponsive to iloprost | Improved 6MWD, haemodynamics and WHO functional class | [35] | |
Prostanoids + sildenafil | 20 | 2 yrs | Not given | Significant improvement in WHO functional class and signs of right heart failureIncrease in 6MWD after 1- and 2-yr follow-up | [36] |
4 | Not given | IPAH, PAH-CTD | Improvements in 6MWD, Ppa and dyspnoea | [37] | |
Bosentan + sildenafil | 9 | 12 months | IPAH | Improvements in 6MWD and CPET | [38] |
3 | ≤24 months | IPAH | Improvement in functional capacity, BNP | [39] | |
11 | 1.1 yrs | IPAH, PAH-CTD | Improvement in WHO functional class, 6MWD and mean Ppa | [40] | |
25 | 3 months | IPAH, PAH-SSc | Improved WHO functional class and 6MWD in IPAH but not in PAH-SSc | [41] | |
10 | 6 months | IPAH, PAH-CTD | Increase in 6MWD | [42] | |
Bosentan + prostanoids | 35 | 3 months | IPAH | Improvements in 6MWD, CI, mean Ppa and WHO functional class | [43] |
Bosentan + iloprost | 40 | 12 weeks | IPAH | No effect on 6MWD | [44] |
67 | 12 weeks | IPAH, APAH | Significant increase in 6MWD and WHO functional classDelay in time to clinical worseningImprovements in mean Ppa and PVR | [16] | |
Sildenafil + beraprost | 1 | 1 month | PAH-SSc | Decrease 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.