SURVIVAL IN PRIMARY PULMONARY-HYPERTENSION WITH LONG-TERM CONTINUOUS INTRAVENOUS PROSTACYCLIN

Objective: To evaluate,the effects of long-term intravenous infusion o f prostacyclin on exercise capacity, hemodynamics, and survival in pat ients with primary pulmonary hypertension. Design: Open, multicenter, uncontrolled trial. Setting: Four referral centers. Patients: 18 patie nts with primary pulmonary hypertension: 1 New York Heart Association (NYHA) class II patient, 13 NYHA class III patients, and 4 NYHA class IV patients. Interventions: Continuous intravenous prostacyclin admini stered by portable infusion pumps. All patients were treated with anti coagulant agents. Measurements and Main Results: With the 6-minute wal k used to evaluate exercise capacity, patients could walk on average m ore than 100 meters farther after prostacyclin therapy was initiated ( distance at 6 months, 370 +/- 119 meters compared with 264 +/- 160 met ers at baseline; P < 0.001; distance at 18 months, 408 +/- 138 meters; P = 0.02 compared with baseline). Hemodynamics were improved at 6 mon ths: The cardiac index increased 18% (95% CI, 0.1% to 36.7%; P = 0.02) , and mean pulmonary artery pressure and total pulmonary resistance de creased 9% (CI, 1.4% to 15.7%; P = 0.03) and 26% (CI, 6.1% to 46.3%; P = 0.02), respectively, compared with baseline. The improvements in ca rdiac index and total pulmonary resistance were maintained at 12 month s (27% increase [CI, 1.3% to 51.9%; P = 0.05] and 32% decrease [CI, 9. 7% to 53.6%; P = 0.02] compared with baseline, respectively). Survival was improved in NYHA class III and IV patients who received continuou s prostacyclin (n = 17; follow-up, 37 to 69 months) when compared with historical controls who received standard therapy (National Institute s of Health Primary Pulmonary Hypertension Registry, n = 31, P = 0.045 ). Kaplan-Meier estimates of 1-, 2-, and 3-year survival rates for the patients treated with prostacyclin were 86.9%, 72.4%, and 63.3%, resp ectively, compared with 77.4%, 51.6%, and 40.6% for the historical con trol group (hazard ratio, 2.9 [CI, 1.0 to 8.0; P = 0.045]). Serious co mplications attributable to the drug and delivery system included two deaths and seven episodes of nonfatal sepsis in three patients. Conclu sions: Continuous intravenous prostacyclin resulted in sustained clini cal and hemodynamic improvement and probably in improved survival in p atients with severe primary pulmonary hypertension. Despite potentiall y serious complications, long-term prostacyclin may be especially help ful in seriously ill patients awaiting transplantation.