Ambrisentan (ABS) is an ETA-selective endothelin receptor antagonist approved for the treatment of pulmonary arterial hypertension (PAH). Patients in the placebo-controlled, 12-week PAH studies (ARIES-1 and ARIES-2) continued treatment with ABS in a long-term study, ARIES-E. This post-hoc analysis examined hemodynamic changes following treatment with long-term ambrisentan monotherapy (2.5, 5, or 10 mg oral once-daily).
Sixty-eight patients who received long-term ABS treatment in the ARIES-E study had post-baseline right heart catheterization (RHC) data; 58 of these 68 patients (85%) were receiving ABS monotherapy. Historical baseline hemodynamic data were assessed prior to the first dose of ABS (mean = 2.8 ± 3.7 months; median = 1.4 months) and follow-up RHC data was collected at various intervals after the first dose of ABS (mean = 15.4 ± 8.5 months; median = 13.5 months).
Baseline hemodynamic data were consistent with moderate PAH; mean pulmonary arterial pressure (mPAP) = 50.8 ± 1 2.8 mmHg; cardiac index = 2.5 ± 0.7 L/min/m2; right atrial pressure = 7.7 ± 4.8 mmHg; pulmonary vascular resistance (PVR) = 856 ± 488 dyn×s×cm-5. Clinically relevant improvements were observed for mPAP (−8.2 mmHg; 95% CI : −11.0 to −5.5), cardiac index (+0.5 L/min/m2; 95% CI :0.3 to 0.7) and PVR (−297 dyn×s×cm-5; 95% CI: −384 to −200). Right atrial pressure did not change significantly with long-term treatment (−0.1 mmHg; 95% CI: −1.7 to 1.4).
Clinically relevant improvements in mPAP, cardiac index, and PVR, were observed in PAH patients receiving long-term treatment with ambrisentan.
Ambrisentan may provide sustained pulmonary hemodynamic benefits for patients with PAH.
James Klinger, Grant monies (from industry related sources) Gilead, Actelion, Lilly, Pfizer; Consultant fee, speaker bureau, advisory committee, etc. Gilead, Actelion, United Therapeutics; No Product/Research Disclosure Information