Table. 1—

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 P_pa, CI, S_v,O₂, and P_a,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 P_paDelay 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 P_pa, 6MWD and Borg dyspnoea scale	[30]
Epoprostenol + sildenafil	5	3 months	IPAH	Improvement in mean P_ra and WHO functional class	[31]
	3	5 months	IPAH, PAH-CHD	Reduced mean P_pa and PVRIncreased 6MWD	[32]
	3	2 h	IPAH	Significant decrease in mean P_pa 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, P_pa 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 P_pa	[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 P_pa 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 P_pa and PVR	[16]
Sildenafil + beraprost	1	1 month	PAH-SSc	Decrease in P_pa and PVRImprovements in 6MWD and WHO functional class	[45]

IPAH: idiopathic PAH; P_pa: pulmonary arterial pressure; CI: cardiac index; S_v,O₂: mixed venous oxygen saturation; P_a,O₂: arterial oxygen tension; CHD: congenital heart disease; 6MWD: 6-min walk distance; RVSP: right ventricular systolic pressure; P_ra: 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.