We hypothesized that giving bosentan to patients with pulmonary arterial hypertension currently receiving epoprostenol, will allow systematic epoprostenol weaning with no decline in World Health Organization (WHO) functional class or exercise capacity, minimize medication side effects, and significantly reduce cost of therapy.
Five patients with primary pulmonary hypertension which were stable with continuous IV infusion of epoprostenol were initiated on 62.5 mg bid of bosentan; the dose was increased to 125 mg bid at Week 4. By Week 12, subjects were weaned down to a goal of at least 25% of epoprostenol dose at study entry. Patients were then admitted to hospital for complete epoprostenol discontinuation. Right-heart catheterization with epoprostenol challenge was performed four to six weeks after epoprostenol discontinuation, and echocardiograms were done at baseline and at 12 and 24 weeks. Exercise capacity was evaluated with monthly measurement of six-minute walk test (6MWT) up to Week 24. Laboratory assessments were carried out monthly.
All patients were titrated to the 25% epoprostenol goal. One patient discontinued the study protocol before complete epoprostenol discontinuation due to significant elevations in alanine aminotransferase levels (>8 times upper limit of normal). The remaining four patients were successfully weaned off epoprostenol. Epoprostenol challenge during catheterization produced no further improvement in pulmonary pressures in any of the four patients. Echocardiography remained unchanged in all five patients. WHO functional class remained unchanged in four out of the five patients and improved from IV to III in one patient. Two of four patients experienced further increases in 6MWT at Week 24; the mean increase was +19.7±33.26% (mean baseline 6MWT was 384.5 ± 171.9 m). There were no significant adverse events observed in the four patients who completed the study.CONCLUSIONS: The use of bosentan in the down-titration and the eventual discontinuation of epoprostenol in patients with stable primary pulmonary hypertension are safe.
Bosentan is as effective as epoprostenol in the management of stable pulmonary arterial hypertension.
Z. Bshouty, None.