Chronic oral sildenafil therapy in severe pulmonary artery hypertension.

BACKGROUND: Sildenafil, a selective phosphor-diesterase-5 inhibitor, may be of clincal benefit in patients with pulmonary artery hypertension.

METHODS AND RESULTS: Fourteen patients, aged 5-30 years, with severe pulmonary artery hypertension (9 with primary pulmonary hypertension, 5 with operated congenital heart disease) received oral sildenafil in addition to conventional therapy. Twelve patients were in New York Heart Association functional class III or IV. The drug was started in low dose and empirically increased. Finally a median dose of 87.5 mg/day was used in children weighing less than 30 kg, and 150 mg/day in those with weight more than 30 kg. The patients were followed up by assessing their functional status, six-minute walk test, Doppler echocardiography and hemodynamic study (in selected cases). On mean follow-up of 7.3+/-2.4 months (range 3-14 months), New York Heart Association functional class improved from 3.31+/-0.75 to 2.00+/-0.71 (p<0.002). There was a remarkable improvement on the six-minute walk test from a baseline of 264.1+/-193.7 m to 408.2+/-156.97 m at 3 months (p<0.001) and 453.2+/-159.81 (p<0.0001) at 6 months. The right ventricular systolic pressure estimated echocardiographically declined from 112.40+/-45.21 mmHg to 101.86+/-47.86 mmHg (p<0.002). The mean pulmonary artery pressure decreased from 62 mmHg to 47 mmHg in 4 patients of primary pulmonary hypertension recatheterized after a mean of 7 months of sildenafil treatment. Clinical improvement was seen even when no decrease in pulmonary artery pressure was demonstrated in one patient with secondary pulmonary artery hypertension. However, 2 patients died during follow-up despite clinical improvement.

CONCLUSIONS: Oral sildenafil was well tolerated and led to an improved clinical condition and exercise performance. Whether the drug improves mortality remains to be established. Larger trials a rewarranted.