PURPOSE: We aimed to assess the effects of sildenafil and evaluate optimal dosing in primary pulmonary hypertension (PPH). Sildenafil selectively inhibits phosphodiesterase 5 (PDE5), which is abundant in pulmonary and penile tissue. This results in increasing nitric oxide (NO) at tissue level leading to pulmonary vasodilatation. SUBJECTS AND METHODS: Our study was a prospective study of sildenafil in 15 consecutive patients with severe symptomatic PPH of NYHA class III-IV. All patients were stabilized for a minimum period of 5 days with antifailure medications. Sildenafil was started at 50 mg twice daily for 4 weeks and increased to 100 mg bid for 4 more weeks in a step-up protocol. Primary end-points were change in Borg dyspnea index, NYHA class and 6-min walk distance, estimated at baseline 1, 2, 4 and 8 weeks. RESULTS: NYHA class (baseline 3.8 +/- 0.4 vs. 4 weeks 2.4 +/- 0.5, p = 0.002), Borg dyspnea index (8.1 +/- 1.7 vs. 4.4 +/- 1.9, p = 0.0007), 6-min walk distance (234 +/- 44 vs. 377 +/- 128 m, p = 0.001) and Pulmonary artery pressure (125 +/- 15 vs. 113 +/- 18 mm Hg p = 0.05) are significantly improved with sildenafil 50 mg bid at 4 weeks. Increasing the dose to 100 mg bid did not produce further benefit. Echocardiography parameters of right heart dimensions and functions did not change markedly in the study period. CONCLUSION: Sildenafil is well tolerated with no adverse effects in severe pulmonary hypertension. It reduces symptoms, improves effort tolerance and controls refractory heart failure significantly by 2 weeks in 70% of patients at 50 mg twice daily. Three patients (20%) failed to respond with sildenafil.
PURPOSE: We aimed to assess the effects of sildenafil and evaluate optimal dosing in primary pulmonary hypertension (PPH). Sildenafil selectively inhibits phosphodiesterase 5 (PDE5), which is abundant in pulmonary and penile tissue. This results in increasing nitric oxide (NO) at tissue level leading to pulmonary vasodilatation. SUBJECTS AND METHODS: Our study was a prospective study of sildenafil in 15 consecutive patients with severe symptomatic PPH of NYHA class III-IV. All patients were stabilized for a minimum period of 5 days with antifailure medications. Sildenafil was started at 50 mg twice daily for 4 weeks and increased to 100 mg bid for 4 more weeks in a step-up protocol. Primary end-points were change in Borg dyspnea index, NYHA class and 6-min walk distance, estimated at baseline 1, 2, 4 and 8 weeks. RESULTS: NYHA class (baseline 3.8 +/- 0.4 vs. 4 weeks 2.4 +/- 0.5, p = 0.002), Borg dyspnea index (8.1 +/- 1.7 vs. 4.4 +/- 1.9, p = 0.0007), 6-min walk distance (234 +/- 44 vs. 377 +/- 128 m, p = 0.001) and Pulmonary artery pressure (125 +/- 15 vs. 113 +/- 18 mm Hg p = 0.05) are significantly improved with sildenafil 50 mg bid at 4 weeks. Increasing the dose to 100 mg bid did not produce further benefit. Echocardiography parameters of right heart dimensions and functions did not change markedly in the study period. CONCLUSION:Sildenafil is well tolerated with no adverse effects in severe pulmonary hypertension. It reduces symptoms, improves effort tolerance and controls refractory heart failure significantly by 2 weeks in 70% of patients at 50 mg twice daily. Three patients (20%) failed to respond with sildenafil.
Authors: Oleg V Evgenov; Pál Pacher; Peter M Schmidt; György Haskó; Harald H H W Schmidt; Johannes-Peter Stasch Journal: Nat Rev Drug Discov Date: 2006-09 Impact factor: 84.694
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