Table 4—

Summary of Sildenafil Use in Pulmonary Arterial Hypertension(SUPER-1) study 81

	Study outline	Patients		Main outcome measures				Side-effects	Comments
	Prospective, randomised, double blind. Oral sildenafil (20, 40 or 80 mg t.i.d.) versus placebo. Duration 12 weeks. Open-label extension (sildenafil 80 mg t.i.d.).	278 patients (69 males, 209 females). 175 IPAH, 84 CTD, 18 CHD.		After 12 weeks: 4 deaths, 9 withdrawals				Main side-effects were headache, flushing and dyspepsia. Visual disturbance dose dependent; not reported at 20 mg. Only 2 serious events considered attributable to Sil: 1 left-heart dysfunction; 1 postural hypotension.	No difference noted between sub-groups. No significant difference in 6MWD between doses, but significant difference in improvement in functional capacity and haemodynamics. Extension study (median follow-up 589 days) with 259 patients: 14 deaths, 15 withdrawals at 1 yr; 8 received additional therapy. Mean change in 6MWD 51 m at 1 yr with overall 1-yr survival 96%.
		Placebo	Sil	Placebo	Sil 20	Sil 40	Sil 80
Subjects n		70	207	70	69	67	71
Mean age yrs		49	51
FC I:II:III:IV		1:32:34:3	0:75:126:6
				Placebo-corrected change
Mean 6MWD m		344	344		+45^#	+46^#	+50^#
				Change from baseline
Mean RAP mmHg		9	9	+0.3	−0.8	−1.1	−1.0
Mean PAP mmHg		56	52	+0.6	−2.1*	−2.6*	−4.7^#
Mean PVR dyn·s·cm⁻⁵		1051	925	+49	−122*	−143*	−261^#
Mean cardiac index L·min⁻¹·m⁻²		2.2	2.4	0	+0.21	+0.24*	+0.37^#
Improvement in FC %				7	28^#	36^#	42^#

Sil: sildenafil; IPAH: idiopathic pulmonary arterial hypertension; CTD: connective tissue disease; CHD: congenital heart disease; 6MWD: 6-min walking distance; FC: functional class; RAP: right atrial pressure; PAP: pulmonary arterial pressure; PVR: pulmonary vascular resistance. ^#: p≤0.001; *: p<0.05 versus placebo. No significant differences noted between dosage groups.