Sildenafil and beraprost sodium have different mechanism for pulmonary vasodilatation. We evaluated the long term efficacy and safety of combination therapy of oral sildenafil and beraprost sodium for patients with primary pulmonary hypertension, which is hypothesized to be more effective than each agent alone.
Four patients with primary pulmonary hypertension (4 female, mean age ± SEM, 39 ± 12 years) were orally administered 50mg of sildenafil bid and 120 or 180 microgram of beraprost sodium qid. We assessed hemodynamics, arterial blood gas, ANP, BNP and NYHA functional class at baseline, 3 months and 12 months after treatment. No patients received neither sildenafil and beraprost sodium before this study.
The NYHA functional class was kept improved in all cases until 12 months (from IV, III to II). Pulmonary vascular resistance was significantly decreased to 664.5 ± 246.6 dyne•sec•cm-5 at 3 months (-40.7%, p=0.0098) and 737.5 ±443.5 dyne•sec•cm-5 at 12 months (-37.2%, p=0.042) from baseline (1105.5 ± 291.9 dyne•sec•cm-5). Pulmonary vascular resistance at 12 months was decreased more than that at 3 months in 2 cases. Systemic blood pressure was not changed at 3 months (111.3 ± 4.3 mmHg) and at 12 months (120.5 ± 18.0 mmHg) compared with baseline (111.0 ± 10.2 mmHg). Compared with baseline (72.2 ± 9.8 Torr), partial pressure of arterial blood oxygen was increased both at 3 months (92.0 ± 11.9 Torr, +29.7%) and at 12 months (91.3 ± 16.7 Torr, +30.8%). ANP and BNP were correlated with mean pulmonary artery pressure. No adverse events were observed.
These data suggest that beneficial effects of improving oxygenation and functional class as well as decreasing pulmonary vascular resistance continued after 12 months of combination therapy with sildenafil and beraprost sodium.
This combination therapy should be considered before introducing continuous intravenous PGI2 infusion.
K. Ishikura, None.