| 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 markers | n = 26 (male 5, female 21) IPAH 22, CTD 3 | Post 16 weeks: One death in Sil groupNo withdrawals | 3 patients on bosentan had admissions to hospital, 2 with fluid retentionNo blood testing abnormalities noted. | Kansas Cardiomyopathy QoL assessment used |
| Bos | Sil | | Bos | Sil | Treatment effect | | |
| Age | 41 | 44 | RV mass | −3 | −8.8 | ns |
| FC I:II:III:IV | 0:0:14:0 | 0:0:12:0 | 6MWD | +59 | +75 | ns |
| BORG score | +0.2 | −1.5 | ns |
| 6MWD | 304 | 290 | BNP fmol/ml | −6 | −19 | ns |
| PASP | 91 | 96 | QoL Score | +27 | +6 | +22* |
| RA volume | 87 | 83 | RA vol | +4 | −4 | ns |
| RV mass (g) | 134 | 160 | DEI | −0.22 | −0.01 | ns |
| CI | 2.2 | 2.4 | TEI index | −0.02 | −0.11 | ns |
| CI | +0.3 | +0.3 | ns |
| 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 therapy | n = 278 (male 69, female 209) IPAH 175, CTD 84, CHD 18 | Post 12 weeks: 4 deaths, 9 withdrawals | | No 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in FC and haemodynamicsAll extension study data based on 80 mg three times daily dose1 year survival data includes 15 withdrawn patients |
| | | | | | | | | Pbo | Sil |
| Age | Pbo | Sil | | Pbo | Sil 20 | Sil 40 | Sil 80 | Headache | 39% | 45% |
| FC | 49 | 51 | 6MWD | | +45* | +46* | +50* | Flushing | 4% | 12% |
| I:II:III:I V | 1:32:34:3 | 0:75:126:6 | Improved FC | 7% | 28%* | 36%* | 42%* | Dyspepsia | 7% | 12% |
| 6MWD | 344 | 344 | Clinical worsening | 7 | 3 | 2 | 5 | Back pain | 11% | 11% |
| RAP | 9 | 9 | Other therapy | 1 | 0 | 1 | 2 | Diarrhoea | 6% | 10% |
| MPAP | 56 | 52 | RAP | +0.3 | −0.8 | −1.1 | −1.0 | Myalgia | 6% | 9% |
| PVR | 1051 | 925 | mPAP | +0.6 | −2.1** | −2.6* | −4.7* | Epistaxis | 1% | 7% |
| CI | 2.2 | 2.4 | PVR | +49 | −122* | −143* | −261* | Insomnia | 1% | 6% |
| CI | 0 | +0.21 | +0.24** | +0.37* | Visual disturbance | 0% | 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 |