Role of Ambrisentan in the Management of Pulmonary Hypertension

Abstract

Objective: To review the role of ambrisentan in the treatment of pulmonary arterial hypertension (PAH). Data Sources: Literature was accessed through MEDLINE (1950-June 2008), Iowa Drug Information Service (1966–March 2008), EMBASE (1966-June 2008), bibliographies of pertinent articles, and unpublished data provided by the manufacturer and the Food and Drug Administration (FDA). Search terms included ambrisentan, endothelin antagonist, pulmonary hypertension, and pulmonary arterial hypertension. Due to limited literature available, additional criteria to limit searches were not used. Study Selection and Data Extraction: Abstracts and original preclinical and clinical research reports available in the English language were Identified for review. All manufacturer-provided data were also evaluated. Literature related to ambrisentan, endothelin antagonists, pulmonary hypertension, and pulmonary arterial hypertension were included. Four clinical trials evaluated the efficacy of ambrisentan in adults with symptomatic PAH. Data Synthesis: Ambrisentan is the latest endothelin-receptor antagonist (ERA) to obtain FDA approval for the treatment of PAH. It joins the first FDA-approved ERA, bosentan. Like bosentan, ambrisentan is available orally (with once-daily dosing compared with bosentan's twice-daily dosing) and has been shown to improve exercise capacity and delay clinical worsening. As with bosentan, the most significant safety concerns with ambrisentan relate to potential liver injury and a contraindication in pregnancy. Although ambrisentan has higher affinity for the endothelin type A receptor than for the endothelin type B receptor, specific advantages of this selectivity, in terms of efficacy compared with bosentan, a nonselective agent, have not been demonstrated. Conclusions: Ambrisentan has been shown to be an effective ERA in patients with PAH. A significant advantage of ambrisentan is the lack of any clinically important drug interactions with warfarin and sildenafil, which are frequently used by patients being treated for PAH.