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

Table 1

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 prostanoids for treatment of pulmonary arterial hypertension in adults.

	Rubin et al. [20]	Barst et al. [21]	Badesch et al. [22]	AIR [23]	Simmoneau et al. [24]	TRIUMPH-1 [25]	FREEDOM-M [26]
Patients (no.)	23	81	111	203	470	235	349
Drug	EPOPROSTENOL			ILOPROST	TREPROSTINIL
Dosing/route	20–40 ng/Kg/min iv.			2.5–5 𝜇g inh. x6–9	20–80 ng/Kg/min sc.	18–54 𝜇g inh. x4	0.125–12 mg bid os
Follow-up (months)	2	3	3	3	3	3	3
Etiology (%)*
IPAH	100	100	—	51	58	56	74
CTD	—	—	100	13	19	33	18
CHD	—	—	—	—	24	—	7
CTEPH	—	—	—	33	—	—	—
Anorexigen use	—	—	—	3	—	—	—
HIV	—	—	—	—	—	—	1
Functional class (%)
NYHA/WHO II	9	—	5	—	11	—	34
NYHA/WHO III	65	75	78	59	82	98	66
NYHA/WHO IV	26	25	17	41	7	2	—
Primary end point	Hemodynamics	Hemodynamics	6MWD	Combined^†	6MWD	6MWD	6MWD
Treatment effects
Δ6MWD (m)	45	47	94	36	16	20	23
Hemodynamics	Improved	Improved	Improved	Improved	Improved	N/A	N/A
Clinical worsening	Reduced	Reduced^‡	No change	Reduced	Reduced	No change	No change
Adverse reactions	Flushing, headache, vomiting, jaw pain, hypotension			Flushing, cough, headache, trismus	Infusion site pain, cough, headache	Pharyngeal pain/throat irritation, cough	Nausea, diarrhea, headache, jaw pain

AIR: Aerosolized Iloprost Randomized; TRIUPMH: TReprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension; FREEDOM-M: Oral Treprostinil as Monotherapy for the Treatment of Pulmonary Arterial Hypertension; iv.: intravenous; inh.: inhalation; sc.: subcutaneous; bid: twice 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); CTEPH: chronic thromboembolic pulmonary hypertension; HIV: human immunodeficiency virus; NYHA: New York Heart Association; WHO: World Health Organization; 6MWD: 6 min walk distance; †combined epoprostenol end point of improvement in NYHA functional class and >10% in 6MWD; Δ: mean (or median) change from baseline;‡ significantsurvival benefit (𝑃=0.003) was observed in epoprostenol patients.