Pulmonary Arterial Hypertension in Adults: Novel Drugs and Catheter Ablation Techniques Show Promise? Systematic Review on Pharmacotherapy and Interventional Strategies

Table 2

Patients, etiology, end points, treatment effects, and adverse reactions in the Pivotal Phase III randomized controlled trials of the US Food and Drug Administration approved endothelin-1 receptor antagonists for the treatment of pulmonary arterial hypertension in adults.

	Channick et al. [27]	BREATHE-1 [28]	EARLY [29]	ARIES-1 [30]	ARIES-2 [30]	SERAPHIN [31]
Patients (no.)	32	213	185	202	192	742
Drug	BOSENTAN			AMBRISENTAN		MACITENTAN
Dosing/route	62.5–125 mg bid/os	62.5–250 mg bid/os	62.5–125 mg bid/os	5 or 10 mg qd/os	2.5 or 5 mg qd/os	3 or 10 mg qd/os
Follow-up (months)	3	4	6	3	3	24
Etiology (%)*
IPAH	85	70	58	63	65	56
CTD	15	30	20	29	30	30
CHD	—	—	17	—	—	8
HIV	—	—	5	5	3	1
Anorexigen use	—	—	—	3	2	3
Functional class (%)
NYHA/WHO II	—	—	100	30	45	52
NYHA/WHO III	100	91	—	60	52	46
NYHA/WHO IV		9	—	10	3	2
Primary end point	6MWD	6MWD	6MWD; Hemodynamics	6MWD	6MWD	Composite/events^†
Treatment effects
Δ6MWD (m)	76	44	19	31 and 51	32 and 59	17 and 22
Hemodynamics	Improved	N/A	Improved	No change	No change	Improved
Clinical worsening	Reduced	Reduced	Reduced	Reduced	Reduced	Reduced
Adverse reactions	Headache, flushing, syncope, anemia, and elevated liver aminotransferase values			Peripheral edema, nasal congestion, and flushing		Anemia, headache, and nasopharyngitis

BREATHE: Bosentan Randomized Trial of Endothelin Antagonist THErapy; EARLY: Endothelin Antagonist tRial in mildLY symptomatic pulmonary arterial hypertension patients; ARIES: Ambrisentan in pulmonary arterial hypertension, RandomIzed, double-blind, placebo-controlled, multicenter, efficacy study; SERAPHIN: Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve cliNical outcome; bid: twice daily; qd: once-daily; os: oral; ∗sum of percentage may not be 100% for rounding to the nearest unit; 0.5 is rounded to the upper unit; IPAH: idiopathic pulmonary arterial hypertension; CTD: connective tissue disease; CHD: congenital heart disease (congenital systemic-to-pulmonary shunts); HIV: human immunodeficiency virus; NYHA: New York Heart Association; WHO: World Health Organization; 6MWD: 6 min walking distance; †primary end point, time from the initiation of treatment to the first occurrence of a composite of death, atrioseptostomy, lung transplantation, initiation of prostanoids, or worsening of PAH; Δ: mean (or median) change from baseline.