Abstract

Background: Pulmonary hypertension is a progressive and often fatal complication of the scleroderma spectrum of disease for which no treatment has been proven effective in a randomized trial. Objective: To determine the effect of epoprostenol on pulmonary hypertension secondary to the scleroderma spectrum of disease. Design: Randomized, open-label, controlled trial. Setting: 17 pulmonary hypertension referral centers. Patients: 111 patients with moderate to severe pulmonary hypertension. Intervention: Epoprostenol plus conventional therapy or conventional therapy alone. Measurements: The primary outcome measure was exercise capacity. Other measures were cardiopulmonary hemodynamics, signs and symptoms of pulmonary hypertension and scleroderma, and survival. Results: Exercise capacity improved with epoprostenol (median distance walked in 6 minutes, 316 m at 12 weeks compared with 270 m at baseline) but decreased with conventional therapy (192 m at 12 weeks compared with 240 m at baseline). The difference between treatment groups in the median distance walked at week 12 was 108 m (95% CI, 55.2 m to 180.0 m) (P < 0.001). Hemodynamics improved at 12 weeks with epoprostenol. The changes in mean pulmonary artery pressure for the epoprostenol and conventional therapy groups were−5.0 and 0.9 mm Hg, respectively (difference, −6.0 mm Hg [CI, −9.0 to −3.0 mm Hg], and the mean changes in pulmonary vascular resistance were −4.6 and 0.9 mm Hg/L per minute, respectively (difference, −5.5 mm Hg/L per minute [CI, −7.3 to −3.7 mm Hg/L per minute]. Twenty-one patients treated with epoprostenol and no patients receiving conventional therapy showed improved New York Heart Association functional class. Borg Dyspnea Scores and Dyspnea-Fatigue Ratings improved in the epoprostenol group. Trends toward greater improvement in severity of the Raynaud phenomenon and fewer new digital ulcers were seen in the epoprostenol group. Four patients in the epoprostenol group and five in the conventional therapy group died (P value not significant). Side effects of epoprostenol therapy included jaw pain, nausea, and anorexia. Adverse events related to the epoprostenol delivery system included sepsis, cellulitis, hemorrhage, and pneumothorax (4% incidence for each condition). Conclusions: Continuous epoprostenol therapy improves exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary hypertension due to the scleroderma spectrum of disease.