Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease - A randomized, controlled trial

Background: Pulmonary hypertension is a progressive and often fatal complic ation of the scleroderma spectrum of disease for which no treatment has bee n proven effective in a randomized trial. Objective: To determine the effect of epoprostenol on pulmonary hypertensio n 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 therap y alone. Measurements: The primary outcome measure was exercise capacity. Other meas ures were cardiopulmonary hemodynamics, signs and symptoms of pulmonary hyp ertension and scleroderma, and survival. Results: Exercise capacity improved with epoprostenol (median distance walk ed in 6 minutes, 316 m at 12 weeks compared with 270 m at baseline) but dec reased with conventional therapy (192 m at 12 weeks compared with 240 m at baseline). The difference between treatment groups in the median distance w alked at week 12 was 108 m (95% CI, 55.2 m to 180.0 m) (P < 0.001). Hemodyn amics 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 m m 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 epop rostenol and no patients receiving conventional therapy showed improved New York Heart Association functional class. Borg Dyspnea Scores and Dyspnea-F atigue Ratings improved in the epoprostenol group. Trends toward greater im provement in severity of the Raynaud phenomenon and fewer new digital ulcer s were seen in the epoprostenol group. Four patients in the epoprostenol gr oup and five in the conventional therapy group died (P value not significan t). Side effects of epoprostenol therapy included jaw pain, nausea, and ano rexia. Adverse events related to the epoprostenol delivery system included sepsis, cellulitis, hemorrhage, and pneumothorax (4% incidence for each con dition). Conclusions: Continuous epoprostenol therapy improves exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary hypertension due t o the scleroderma spectrum of disease.