A randomized, placebo-controlled, double-blind, crossover study to evaluate the efficacy of oral sildenafil therapy in severe pulmonary artery hypertension.

BACKGROUND: Severe pulmonary artery hypertension (PAH) is a disorder with limited treatment options. Recently, several newer drugs have recently been introduced to treat PAH. Sildenafil is one which has shown promise in several uncontrolled studies, but controlled trials have been few. In this randomized placebo-controlled study, we evaluated the efficacy of oral sildenafil in idiopathic PAH and PAH caused by Eisenmenger syndrome.

METHODS: This was a randomized, double-blind, placebo-controlled crossover study. Twenty patients, 10 of each of idiopathic PAH and Eisenmenger syndrome, were randomized to receive placebo or sildenafil in a double-blind manner for 6 weeks and, after a washout period of 2 weeks, were crossed over. The primary end point of efficacy was the improvement in distance covered in 6-minute walk test. Secondary end points were reduction in pulmonary artery pressure as measured by Doppler echocardiography after 6 weeks of treatment, improvement in clinical condition, New York Heart Association (NYHA) class, and exercise duration and metabolic equivalents (Mets) achieved on modified Bruce exercise protocol.

RESULTS: There was significant improvement in primary and secondary end points. The primary end point of distance covered in 6-minute walk test improved from 262 +/- 99 to 358.9 +/- 96.5 m (P < .0001) after treatment with sildenafil. Pulmonary artery pressure, the secondary end point, improved from the baseline of 98.8 +/- 20.5 to 78.3 +/- 15.3 mm Hg (P < .0001), NYHA class improved from 2.65 +/- 0.59 to 1.55 +/- 0.51 (P < .0001), exercise duration from 6.4 +/- 3.1 to 10.2 +/- 2.05 minutes (P < .0001), and Mets achieved from 3.32 +/- 1.57 to 6.04 +/- 1.87 (P < .0001) after treatment with sildenafil. There was no significant fall in blood pressure with placebo and sildenafil, and no serious side effects of drug were observed in the study.

CONCLUSIONS: Sildenafil significantly improved the symptomatic status, exercise capacity, NYHA class, and hemodynamic parameters of patients with severe PAH and can be safely used as a primary or adjunctive treatment of the same.