NEW YORK (Reuters Health) – In patients with pulmonary arterial hypertension (PAH), ambrisentan may be an alternative to bosentan or sitaxsentan when those agents cause liver problems, according to a report in the January issue of Chest.

“The drug is a viable option for being a part of the PAH treatment armamentarium,” Dr. Michael D. McGoon told Reuters Health.

Dr. McGoon from the Mayo Clinic, Rochester, Minnesota and colleagues examined the incidence of increased serum aminotransferase concentrations and the overall safety of ambrisentan in 36 patients who had previously discontinued other endothelin receptor antagonists because of increased serum aminotransferase concentrations.

The patients were given 2.5 mg ambrisentan daily for 4 weeks and then 5 mg/d for 8 weeks. None of the patients experienced serum AST or ALT increases that required discontinuation of ambrisentan during the 12-week study, the investigators report.

One patient had a transient elevation in ALT concentration to 3.2 times the upper limit of normal at week 12, the researchers note. This resolved following a temporary dose reduction to 2.5 mg and did not recur when the dose was returned to 5 mg and then increased to 10 mg daily.

“No additional aminotransferase levels more than 3 times the upper limit of normal were observed with long-term treatment (median exposure, 102 weeks) despite dose increases to 10 mg qd in more than half the patients,” the team reports.

Ambrisentan therapy was associated with significant improvements in exercise capacity and decreases in WHO class III symptoms, the researchers found, and patients treated with ambrisentan experienced significant improvements in 6 of the 8 domains of the SF-36 health survey and the composite physical health score.

Dr. McGoon said that the manufacturer (Gilead Sciences, Westminster, Colorado) intends to look at the drug in other pulmonary hypertension populations, such as interstitial pulmonary fibrosis.

“We would always like to see comparative studies versus other drugs,” Dr. McGoon added, “but that’s not likely to happen.”

Reference:
Chest 2009;135:122-129.