PURPOSE: Ambrisentan is a highly selective oral endothelin receptor antagonist (ERA) shown to improve exercise capacity and delay clinical worsening in pulmonary arterial hypertension (PAH). Little is known of its effects on right heart structure and function with long-term therapy. We evaluated right-sided cardiac variables from surveillance echocardiograms and 6-minute walk distance (6MWD) in patients on maximum therapy.
METHODS: Cohort included six medication-naive females, mean age 48±5 years, with PAH (2 CREST, 2 idiopathic PAH, 2 SLE) and WHO class II symptoms. Study protocol included a 12-week lead-in dose of ambrisentan, thereafter maximized to 10 mg daily. 6MWD was recorded at baseline, 3, 6, 9 months and up to 3.25 years on maximum dose therapy. Echocardiographic variables were recorded at baseline and repeated at intervals between 12 and 24 weeks, and beyond 60 weeks. Paired t test was used for statistical analysis, and values expressed as mean ± SE.
RESULTS: Mean 6MWD at baseline was 391±5 m. There was a significant increase in 6MWD from baseline after lead-in dosing (+37.8±9.4 m, p=0.01), 3 months (+66.0±16, p=0.009) and 6 months on optimal dosing (+57.1±17 m, p=0.02). One patient died of a pulmonary embolism 15 months into the study, but the 5 survivors had a mean increase in 6MWD of 57.3±11 m (p=0.006) beyond 36 months of treatment. Mean right ventricular systolic pressure at baseline was 77.7±6 mmHg, size 3.8±0.4 cm, ejection fraction 36.7±4%. No significant changes in these indices were observed during the study period. Two patients improved from WHO class II to class I, two remained in WHO class II, and two progressed to WHO class III.
CONCLUSION: In this small cohort of females with moderate PAH, right heart indices did not worsen significantly during more than 3 years of ambrisentan 10 mg daily. Improved and sustained exercise capacity was noted on long-term follow up.
CLINICAL IMPLICATIONS: Future studies with larger cohorts are needed to assess the impact of ERA on right heart indices.
DISCLOSURE: Louie Kostopoulos, Consultant fee, speaker bureau, advisory committee, etc. Dr. Zwicke is a financially reimbursed speaker for Gilead, but Gilead acquired the company that makes ambrisentan after the period of time the drug was studied for this abstract.; No Product/Research Disclosure Information