TABLE 1

Evidence-based monotherapy treatment algorithm for drugs that target the prostacyclin pathway

Recommendation	Evidence	PAH severity
Recommendation	Evidence	WHO FC II	WHO FC III	WHO FC IV
Recommended (class I)	Data derived from multiple randomised clinical trials or meta-analyses, or from a single randomised clinical trial or large nonrandomised studies	Selexipag oral^#	Epoprostenol i.v.^¶; iloprost inhaled⁺; treprostinil s.c. and inhaled^§; selexipag oral^#	Epoprostenol i.v.
Should be considered (class IIa)	Consensus of opinion of the experts and/or small studies, retrospective studies and registries		Iloprost i.v.⁺; treprostinil i.v.^§
May be considered (class IIb)	Data derived from a single randomised clinical trial or large nonrandomised studies		Beraprost oral^ƒ; treprostinil oral	Iloprost inhaled and i.v.; treprostinil s.c., i.v. and inhaled

Recommendation IA for prostanoid use in sequential combination therapy for inadequate clinical response at maximal therapy [3]. WHO: World Health Organization; FC: functional class. ^#: not approved at the time of publication; ^¶: approved for continuous i.v. administration for pulmonary arterial hypertension (PAH) WHO FC III–IV by the US Food and Drug Administration (FDA) in 1995; ⁺: approved for aerosol administration for PAH WHO FC III in the European Union and Australia in 2003, and PAH WHO FC III–IV by the FDA in 2004; ^§: approved for s.c. administration for PAH WHO FC II–IV by the FDA and Health Canada in 2002; ^ƒ: approved for oral administration for idiopathic PAH in Japan in 1995 [36]. Information from [15, 16].