Source: DGNews  |  Posted 3 years ago

By Maggie Schwarz

PHILADELPHIA -- November 4, 2008 -- Ambrisentan is a potential treatment for patients with pulmonary arterial hypertension (PAH) who fail to respond to other endothelin receptor antagonists due to liver function test abnormalities, according to researchers speaking here at CHEST 2008, the annual meeting of the American College of Chest Physicians.

Anne Keogh, MD, MBBS, Victor Chang Cardiac Transplant Institute and University of New South Wales, Sydney, Australia, evaluated the incidence of liver function test abnormalities in a subgroup of patients enrolled in the ARIES-3 study who had previously discontinued sulfonamide-based endothelin receptor antagonist (ERA) therapy such as bosentan and/or sitaxsentan due to the development of serum aminotransferase abnormalities.

Oral ERAs have proven effective in the treatment of PAH and have important safety and tolerability profiles, Dr. Keogh explained in a presentation here on October 29. Sulfonamide-based ERAs are associated with dose-dependent increases in alanine aminotransferase (ALT)/aspartate aminotransferase (AST) of >3 times the upper limit of normal and a potential for hepatotoxicity. Ambrisentan is an ERA that was approved for PAH in the United States, Canada, and Europe.

Dr. Keogh presented results obtained in a subgroup of patients enrolled in the ARIES-3 study. The study is an ongoing long-term evaluation of the efficacy and safety of ambrisentan in a broad population of patients with PAH and pulmonary hypertension (PH) due to other aetiologies. The subgroup consisted of 26 patients who had discontinued prior ERA therapy due to liver function test abnormalities and received treatment with ambrisentan 5 mg once daily for 24 weeks.

After the initial 24-week treatment period, investigators could adjust the dose of ambrisentan as indicated. Serum levels of ALT/AST were monitored with laboratory tests every 4 weeks.

Results showed that 25 patients (96%) experienced no liver function test abnormalities.

One patient (4%) experienced increases in ALT/AST levels to >3 times the upper limit of normal, but these levels decreased within 2 weeks.

Patients remained on ambrisentan with no further incidence of liver function test abnormalities, Dr. Keogh said, and concluded that patients who previously could not tolerate bosentan and/or sitaxsentan due to liver function abnormalities could safely receive long-term ambrisentan treatment.

Funding for this study was provided by Gilead Sciences, Inc.

[Presentation title: ARIES-3: Long-Term Ambrisentan Therapy in Patients With Pulmonary Hypertension Who Previously Discontinued Bosentan or Sitaxsentan Due to Liver Function Abnormalities. Abstract AP2206]