Long-term outcome of bosentan treatment in idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with the scleroderma spectrum of diseases

Background: Bosentan improves clinical outcomes in pulmonary arterial hypertension (PAH), particularly in the idiopathic (IPAH) subset. Scant data are available regarding PAH associated with the scleroderma spectrum of diseases (APAH-SSD). Here we review our experience with bosentan in these 2 groups. Methods: Included were all patients, at our center with either IPAH or APAH-SSD in whom bosentan was the first-tine, single-agent therapy with at least 6 months of follow-up. Changes in the World Health Organization (WHO) functional class from baseline to the most recent follow-up on monotherapy were compared between the 2 groups, as well as overall survival and time to a composite end point of hepatotoxicity requiring discontinuation, use of additional therapy, or death. Results: Nineteen IPAH and 17 APAH-SSD subjects with similar baseline clinical characteristics and a median follow-up 9 months (range, 6 - 44) were analyzed. In IPAH subjects, WHO class improved from 3.1 +/- 0.5 at baseline to 2.4 +/- 0.8 (P = 0.005). No change occurred in the APAH-SSD group: 2.9 +/- 0.3 vs. 2.8 +/- 0.8;p = 0.5. Hepatotoxicity requiring discontinuation developed in 6 patients (17%). Seven (37%) IPAH and 8 SSD patients (47%) reached the composite end point (p = NS). Overall survival at I and 2 years was 100% and 100% vs 87% and 79% for IPAH and APAH-SSD patients, respectively (P 0.075). Conclusions: First-line bosentan monotherapy is associated with long-term improvement in functional class and good overall survival in patients with WHO class III IPAH. Most APAH-SSD patients experienced stability or decline in functional class and tended to have a higher mortality.