Conference: 2014 International PHA Conference and Scientific Sessions
Release Date: 06.22.2014
Presentation Type: Abstracts
File Download: 2014 Conference Abstract - Pulido
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Purpose: Ambrisentan (ABS) is an oral, once−daily ETA−selective endothelin receptor antagonist approved for the treatment of pulmonary arterial hypertension (PAH) in patients with WHO class II or III symptoms (5 and 10mg once daily).
Methods: 178 patients with idiopathic PAH (IPAH) and 94 patients with PAH associated with connective tissue diseases (CTD) received 5 or 10mg ABS in the ARIES−1, ARIES−2, or ARIES−E studies. Presented is a subgroup analysis of long−term efficacy and safety in patients with IPAH or CTD. Data are presented for the 5 and 10mg treatment groups combined with last observation carried forward for missing data. However, the majority of patients had 6−minute walk (6MWD) data at 2 years (IPAH: 75%; CTD: 62%).
Results: Kaplan−Meier (K−M) estimates of long−term survival at 1 year were 94% (95% CI: 90% to 97%) for IPAH and 91% (95% CI: 82% to 95%) for CTD. K−M estimates of long−term survival at 2 years were 89% (95% CI: 83% to 93%) for IPAH and 87% (95% CI: 77% to 92%) for CTD. The change from baseline in 6MWD at 2 years was +38m (95% CI: 24 to 52) for IPAH and +1m (95% CI: −18 to 20) for CTD. Changes from baseline at 2 years in Borg dyspnea index (BDI) and WHO functional class (WHO−FC) were similar between IPAH and CTD subjects (data not shown). Long term ABS treatment was generally well tolerated. 3 IPAH patients and 1 CTD patient experienced an adverse event (AE) of peripheral edema that was considered severe by the investigator; only 1 AE of peripheral edema lead to study d/c (IPAH). Five IPAH patients and 7 CTD patients reported aminotransferase abnormalities (ALT/AST>3xULN) during the 2 year treatment period; 3 of these events led to study d/c (IPAH=1, CTD=2).
Conclusions: ABS treatment was associated with favorable long−term survival in IPAH and in CTD patients. IPAH patients showed sustained improvements in 6MWD whereas baseline 6MWD was maintained for patients with PAH associated with CTD.