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

Table 3

Patients, etiology, end points, treatment effects, and adverse reactions of the US Food and Drug Administration approved phosphodiesterase type-5 inhibitors in the pivotal Phase III randomized controlled trials for treatment of pulmonary arterial hypertension in adults.

	SUPER-1 [32]	PHIRST [33]
Patients (no.)	278	405
Drug	Sildenafil	Tadalafil
Dosing/route	20, 40 or 80 mg tid/os	2.5, 10, 20, or 40 mg qd/os
Follow-up (months)	3	4
Etiology (%)*
IPAH	64	60
CTD	30	24
CHD	6	11
Anorexigen use	—	4
Functional class
NYHA/WHO II	36	34
NYHA/WHO III	61	62
NYHA/WHO IV	3	2
Primary end point	6MWD	6MWD
Treatment effects
Δ6MWD (m)	45, 46, and 50	14, 20, 27 and 33^†
Hemodynamics	Improved	Improved^¶
Clinical worsening	Reduced	Reduced^#
Adverse reactions	Epistaxis, headache, dyspepsia, flushing	Headache, myalgia, back pain, flushing

SUPER: Sildenafil Use in Pulmonary artERial hypertension; PHIRST: Pulmonary Arterial HypertensIon and ReSponse to Tadalafil; tid: three times daily; os: oral; qd: once-daily; ∗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 (systemic-to-pulmonary shunts); NYHA: New York Heart Association; WHO: World Health Organization; 6MWD: 6 min walk distance; Δ: mean (or median) change from baseline; †only the 40 mg dose met the prespecified level of statistical significance (𝑃<0.01); ¶improvements were observed only with 20 and 40 mg doses in mean pulmonary arterial pressure and pulmonary vascular resistance; #only the 40 mg dose improved the time to clinical worsening, incidence of clinical worsening, and quality of life.