O-024 Outcome Research In 77 Patients With Pulmonary Arterial Hypertension Receiving Sildenafil: A Double-blind, Randomised Controlled Study

Purpose

PAH resulting from CHD – a major cause of postoperative morbidity and death. Sildenafil: selective inhibitor of phosphodiesterase-5 - an effective and promising pulmonary vasodilator, with minors reverse effects.

Methods

This monocentric, randomised placebo-controlled study evaluated the efficacy, safety, tolerability of oral Sildenafil in children with severe PAH secondary congenital shunts (simple (14 patients), mixed (35), complex (28)). 77 PAH patients (35 – repaired shunts, 31 – palliative, 11 inoperable) assigned to placebo or Sildenafil – dose of 1–2 mg/kg/day each 8h: 6–12 months. Sildenafil group - 38 (mean age 19, 9 ± 5, 3 months: 16 boys/22 girls); placebo – 39 (mean age 21, 7 ± 7, 8 months: 22 boys/17 girls). Research protocol: FC NYHA; 6-min walk test; O2 saturation; echocardiography PAPm, myocardial performance index (MPI/Tei index), right cardiac catheterisation – PVRI; questionnaire for adverse reactions was available.

Results

Sildenafil patients improved FC from 3,16 ± 0, 1–2, 15 ± 0,1 (p < 0,001); effort tolerance (+152,5 ± 17,4m – 6 months and +184,3 ± 21,2 m - 12 months of treatment), (p < 0,001); O₂ saturation (+3,1 ± 0,5%) but placebo (+0,6 ± 0,3%), (p < 0,001); PAPm decreased: 22,0 ± 2,22 at 6 months with 19,03 ± 2,3 mmHg - 12 months (p < 0,001); PVRI decreased: 2,45 ± 0,19 UWood·m² (p < 0,001); Tei index with 0,15 ± 0,01(-31%) to initial (p < 0,001). In placebo group only PVRI diminished from 6,4 ± 0,1 to 5,7 ± 0,3 UW/m² (p < 0,05). No death in the Sildenafil group, but 5 in placebo.

Conclusions

Sildenafil – efficient in treating severe PAH secondary to congenital shunts, but even more effective in children after cardiac surgery. Sildenafil improves FC, effort tolerability, O₂ saturation, RV global function, diminishing PAPm and PVRI comparing with placebo. Sildenafil has good safety, tolerability, favourable impact on life quality – insignificant adverse reactions.