TABLE 2

Effect of pulmonary arterial hypertension (PAH) medications on health-related quality of life (HRQoL) measures

Study [ref.]	Subjects n	Drug	HRQoL measurement	Time to measurement	Domains significantly improved^#
ERAs
ARIES-1 [26]	201	Ambrisentan 2.5–10 mg	SF-36		Physical: none; mental: none
ARIES-2 [26]	192	Ambrisentan 2.5–5.0 mg	SF-36	12 weeks	Physical: function; mental: none
EARLY [27]	185	Bosentan	SF-36	24 weeks	Physical: none; mental: none; health transition index
SERAPHIN [29]	742	Macitentan 3 or 10 mg	SF-36 version 2	6 months	Physical: function, role, pain; mental: vitality, social function, emotional role, mental health
PDE5 inhibitors and sGC stimulators
Sildenafil in PPH [32]	22	Sildenafil 25, 50 or 100 mg	CHFQ	6 weeks	Dyspnoea, fatigue
SUPER-1 [31]	278	Sildenafil (pooled 20, 40 or 80 mg doses)	SF-36	12 weeks	Physical: function, general health; mental: vitality
SUPER-1 [31]	278	Sildenafil (pooled 20, 40 or 80 mg doses)	EQ-5D	12 weeks	Utility index score
PHIRST [30]	405	Tadalafil 40 mg	SF-36		Physical: function, role, pain, general health; mental: vitality, social function
PHIRST [30]	405	Tadalafil 40 mg	EQ-5D		Visual analogue scale; UK utility index score; USA utility index score
PATENT-1 [28]	443	Riociguat	EQ-5D		ns
PATENT-1 [28]	443	Riociguat	LPH		Significant
Prostanoids and prostacyclin receptor agonists
Epoprostenol in PPH [34]	81	Epoprostenol	CHFQ		Dyspnoea, fatigue, emotional function, mastery
Epoprostenol in PPH [34]	81	Epoprostenol	NHP		Emotional reaction, sleep
Treprostinil s.c. in PAH [39]	470	Treprostinil	MLHFQ		Physical score
Iloprost for severe PH [37]	203	Inhaled iloprost	EQ-5D		Overall health status (visual analogue scale)
Iloprost for severe PH [37]	203	Inhaled iloprost	SF-12		ns
Beraprost for PAH [33]	116	Beraprost	MLHFQ	3, 6, 9 and 12 months	ns
Treprostinil in CTD-PAH [38]	90	Treprostinil	MLHFQ		ns
GRIPHON [41]	1156	Selexipag	None reported
Combination therapy
PACES [40]	267	Sildenafil added to epoprostenol	SF-36		Physical: function, role, general health; mental: vitality, social functioning, mental health
TRIUMPH [36]	235	Treprostinil added to oral bosentan or sildenafil therapy	MLHFQ		Global, physical scores
AMBITION [35, 42]	500	Upfront ambrisentan and tadalafil	None initially reported; CAMPHOR, SF-36		Improved only health transition score in SF-36 versus monotherapy; both arms improved all domains of both instruments

ERA: endothelin receptor agonist; SF-36: Medical Outcomes Study 36-item short form; PDE5: phosphodiesterase type 5; sGC: soluble guanylate cyclase; PPH: primary pulmonary hypertension; CHFQ: Chronic Heart Failure Questionnaire; EQ-5D: EuroQol Group 5-Dimension Self-Report Questionnaire; ns: non-significant; LPH: Living with Pulmonary Hypertension questionnaire; NHP: Nottingham Health Profile; MLHFQ: Minnesota Living with Heart Failure Questionnaire; CTD: connective tissue disease; SF-12: Medical Outcomes Study 12-item short form; CAMPHOR: Cambridge Pulmonary Hypertension Outcome Review. ^#: compared with placebo. Information condensed and updated from [22].