Ambrisentan (Volibris®; GlaxoSmithKline) is safe, tolerable, and possibly effective for improving hemodynamics in patients with pulmonary arterial hypertension (PAH), according to an interim report on a postmarketing surveillance study published in Clinical Drug Investigation.
A total of 702 patients with PAH were included in this safety analysis of ambrisentan (ClinicalTrials.gov identifier: NCT01406327). Of these patients, 77.8% were defined as World Health Organization functional class II/III. In addition, approximately 88.5% of patients were taking other PAH medications at the time of treatment initiation.
On average, patients were provided a daily ambrisentan dose of 5.9±2.7 mg and were observed for 392.7 days. Adverse events related to therapy (324 total) were observed in 204 patients (29.1%), including epistaxis (2.1%), abnormal hepatic function (2.3%), edema and face edema (2.6% each), headache (3.6%), peripheral edema (4.1%), and anemia (4.6%). A total of 385 serious adverse events occurred in 184 (26.2%) patients.
Cases of interstitial lung disease were reported in approximately 1.6% of patients; however, the investigators were unable to determine whether ambrisentan played a role in these cases. Hemodynamic parameters improved in treated patients, as assessed by changes in pre- and post-treatment mean pulmonary arterial pressure (42.48±12.29 mm Hg to 34.31±12.72 mm Hg) and pulmonary vascular resistance (772.89±721.94 dyn s cm-5to 403.63±309.66 dyn s cm-5).
The investigators noted that certain clinical parameters were not consistently recorded in patients, thereby limiting the efficacy analysis of the drug.
Cases of edema occurred primarily 1 month following treatment initiation, and the investigators suggested that “administration and subsequent dose increases of diuretics within a month after the beginning of treatment with ambrisentan” may be warranted if this occurs in clinical practice or future research.
Takahashi T, Hayata S, Kobayashi A, Onaka Y, Ebihara T, Hara T. Surveillance on the safety and efficacy of ambrisentan (Volibris tablet 2.5 mg) in patients with pulmonary arterial hypertension in real clinical practice: post-marketing surveillance (interim analysis report) [published online December 27, 2017]. Clin Drug Investig. doi:10.1007/s40261-017-0602-4