Background Pulmonary arterial hypertension (PAH) is a devastating disease of the small pulmonary arteries and arterioles, characterized by intimal fibrosis, medial hypertrophy and plexiform lesions. When untreated both the idiopathic form (IPAH, formerly termed primary pulmonary hypertension, PPH) and PAH related to various other conditions such as scleroderma (SSc) often take a progressive course with high mortality. There is ongoing search for disease-specific treatments that are able to improve survival in these patients. The oral dual endothelin (ETA/ETB) antagonist bosentan has been shown to improve exercise capacity, time to clinical worsening, haemodynamics and quality of life in short-term studies.
Materials and methods To determine the long-term effects of bosentan on survival, patients from the two double-blind, randomized trials and their open-label extensions, treated with first-line bosentan, were followed for up to 3 years. Data on survival were collected between September 1999 (first patient included in the placebo-controlled trials) and December 2002. Vital status was verified in each patient. The survival cohorts of these patients were compared with either the predicted survival for each patient based on an equation from the National Institutes of Health (NIH) PPH registry or with historical controls.
Results Observed survival up to 36 months was reported as a Kaplan-Meier estimate in three cohorts: (1) In 169 PPH patients treated with first-line bosentan, 1- and 2-year survival was 96% and 89%, respectively, vs. predicted untreated survival at 1 and 2 years of 69% and 57%, respectively; (2) in 50 patients with PAH associated with SSc (PAH-SSc), 1-, 2- and 3-year survival was 82%, 67% and 64%, respectively, vs. ∼45%, ∼35% and ∼28%, respectively, from registry data of untreated PAH-SSc patients; and (3) in 139 PPH patients in WHO functional class III, 1- and 2-year survival was 97% and 91%, respectively, vs. 91% and 84% in a historical cohort of 346 patients treated with epoprostenol in five major referral centres.
Conclusions The present analyses suggest that first-line bosentan therapy, followed by the addition of other disease-specific therapies as required, improves survival in patients with advanced PAH.