Table 6 Phosphodiesterase type 5 inhibitors: randomised studies
Study characteristicsPatientsOutcome measuresSide effectsComments
Wilkins et al 2005128 (SERAPH) P R DB Oral sildenafil (50 mg three times daily) vs bosentan (125 mg twice daily) Duration 16 weeksOutcomes: 1. RV mass on MRI2. 6MWD, BORG, QOL, BNP, Echo markersn = 26 (male 5, female 21) IPAH 22, CTD 3Post 16 weeks: One death in Sil groupNo withdrawals3 patients on bosentan had admissions to hospital, 2 with fluid retentionNo blood testing abnormalities noted.Kansas Cardiomyopathy QoL assessment used
BosSilBosSilTreatment effect
Age4144RV mass−3−8.8ns
FC I:II:III:IV0:0:14:00:0:12:06MWD+59+75ns
BORG score+0.2−1.5ns
6MWD304290BNP fmol/ml−6−19ns
PASP9196QoL Score+27+6+22*
RA volume8783RA vol+4−4ns
RV mass (g)134160DEI−0.22−0.01ns
CI2.22.4TEI index−0.02−0.11ns
Galie et al 2005127 (SUPER 1) P R DB (E) Oral sildenafil (randomised to 20 mg, 40 mg or 80 mg three times daily) vs placeboDuration: 12 weeksLong term OL extension (sildenafil 80 mg three times daily only) Outcomes: 1. 6MWD 2. Haemodynamics, FC, time to clinical worsening, requirement for other therapyn = 278 (male 69, female 209) IPAH 175, CTD 84, CHD 18Post 12 weeks: 4 deaths, 9 withdrawalsNo difference noted between sub-groupsNo significant difference in 6MWD between doses, but significant difference in improvement in FC and haemodynamicsAll extension study data based on 80 mg three times daily dose1 year survival data includes 15 withdrawn patients
AgePboSilPboSil 20Sil 40Sil 80Headache39%45%
I:II:III:I V1:32:34:30:75:126:6Improved FC7%28%*36%*42%*Dyspepsia7%12%
6MWD344344Clinical worsening7325Back pain11%11%
RAP99Other therapy1012Diarrhoea6%10%
CI0+0.21+0.24**+0.37*Visual disturbance0%5%
Extension study (median follow up 589 days) n = 259 4 deaths, 15 withdrawals at 1 year8 received additional therapy Mean change in 6MWD 51 m at 1 year Overall 1 year survival 96%Visual disturbance dose dependant, not reported at 20 mg doseOnly 2 serious events considered attributable to sildenafil: • 1 Left heart dysfunction• 1 Postural hypotension