TABLE 1.

Overview of therapies targeting the prostacyclin pathway

PGI2 therapy	Approval		WHO FC indication	Mode of administration	Frequency of administration	Half-life	ESC/ERS class of recommendation# and level of evidence for use as monotherapy¶ [3, 17]
	Europe	USA					WHO FC II		WHO FC III		WHO FC IV
							Class	Level	Class	Level	Class	Level
Flolan [18] (epoprostenol)	+	+	III–IV	Intravenous	Continuous	<6 min [24]			I	A	I	A
Veletri+ [19, 20] (epoprostenol)	+	+	III–IV	Intravenous	Continuous
Remodulin [6, 21] (treprostinil)	+##	+	II–IV	Intravenous	Continuous	34 min [25]			IIa	C	IIb	C
Remodulin [6, 21] (treprostinil)	+##	+	II–IV	Subcutaneous	Continuous	85 min [25]			I	B	IIb	C
Tyvaso [8] (treprostinil)	–	+	III	Inhaled	4 times per day, with each inhalation taking up to 3 min [8, 26]	NA			I	B	IIb	C
Orenitram [11] (treprostinil)	–	+	II–III	Oral	2–3 times per day	3–4 h [24]			IIb	B
Ilomedin§ [7] (iloprost)	–	–	III–IV	Intravenous	Over 6 h daily	20–25 min [24]			IIa	C	IIb	C
Ventavis [9, 10] (iloprost)	+	+	III–IV	Inhaled	6–9 times per day, with each inhalation taking 3–10 min, depending on dose and nebuliser device [9]				I	B	IIb	C
Dornerƒ [15] (beraprost)	–	–	NA	Oral	3–4 times per day	45 min [24]			IIb	B
Uptravi [12, 13] (selexipag)	+	+	II–III	Oral	2 times per day	6.2–13.5 h¶¶ [12]	I	B	I	B

PGI₂: prostaglandin I₂ (prostacyclin); WHO FC: World Health Organization functional class; ESC: European Society of Cardiology; ERS: European Respiratory Society; NA: not available. ^#: I, evidence and/or general agreement that a given treatment or procedure is beneficial, useful or effective; II, conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure; IIa, weight of evidence/opinion is in favour of usefulness/efficacy; IIb, usefulness/efficacy is less well established by evidence/opinion; III, evidence or general agreement that the given treatment or procedure is not useful/effective and in some cases may be harmful. ^¶: A, data derived from multiple randomised clinical trials or meta-analyses; B, data derived from a single randomised clinical trial or large nonrandomised studies; C, consensus of opinion of the experts, and/or small studies, retrospective studies or registries. ⁺: known as Caripul in some countries. ^§: approved in New Zealand. ^ƒ: approved in Japan and South Korea [22], a modified-release version is available (Careload [14] and Berasus [23]) and can be administered twice per day. ^##: approved in the European Union, except Ireland, Spain and the UK [21]. ^¶¶: active selexipag metabolite.