Calendar | For Your Patients | PHA Main Site | Contact Us | About Us | Not a registered user? Sign up here.

Resource Library

ATHENA-1: Long Term Clinical Improvements Following the Addition of Ambrisentan to Background PDE5i Therapy in Patients with Pulmonary Arterial Hypertension

Shelley Shapiro

H. Gillies

M. Allard

C. Blair

Ronald Oudiz


  Sign in to add a review

Leave a Comment

Conference: 2012 International PHA Conference and Scientific Sessions

Release Date: 06.22.2012

Presentation Type: Abstracts

Shapiro S1; Gillies H2; Allard M2; Blair C2; Oudiz RJ3

1West Los Angeles VA HealthCare UCLA School of Medicine, Los Angeles, CA, USA; 2Gilead Sciences Inc., Foster City, CA, USA; 3LA Biomedical Research Institute at Harbor-UCLA, Torrance, CA, USA.

BACKGROUND: Ambrisentan is an ETA-selective endothelin receptor antagonist approved for the treatment of pulmonary arterial hypertension (PAH). ATHENA-1 was an open-label efficacy and safety study of the addition of ambrisentan therapy to PAH patients with a sub-optimal response to phosphodiesterase-5 inhibitor (PDE5i) therapy. At 24 weeks, ambrisentan was well tolerated and provided clinically relevant improvements in hemodynamic parameters (mPAP, cardiac index and PVR) and exercise ability. The 48-week data is now presented here.

METHODSEntry criteria included WHO functional class III symptoms and a pulmonary vascular resistance (PVR) of ≥ 400 dyne.sec/cm5. Patients received 5mg ambrisentan once-daily for 4 weeks with the dose increased to 10mg once-daily for an additional 44 weeks. The 48-week endpoints include: survival; time to clinical worsening; change in WHO functional class, 6-minute walk distance (6MWD), Borg Dyspnea Index (BDI), and NT-proBNP.

RESULTSThirty-three subjects received ambrisentan at the start of the study. At 48 weeks the Kaplan Meier survival was 96% (95% CI: 89% to 100%) and freedom from clinical worsening (percent event free) was 80% (95% CI: 66% to 94%). Nearly all (97%) patients improved or maintained their WHO functional class through 48 weeks. At baseline, 6MWD was 362±99 m, BDI score was 3.7±2.1, and NT-proBNP was 717±618 ng/L. At 48 weeks, 6MWD (+15 m, 95% CI: -15 to 44), BDI (-0.7, 95% CI: -1.4 to +0.1), and NT-pro BNP (-35%, 95% CI: -53% to -10%) were numerically improved. The most frequent adverse events were nasal congestion, headache and upper respiratory tract infection. Eight subjects (24%) discontinued study drug due to adverse events.

CONCLUSIONSLong term addition of ambrisentan therapy to PAH patients with a sub-optimal response to PDE5i therapy was well tolerated and demonstrated improvements in 6MWD, WHO functional class, BDI, and NT-proBNP as well as high survival rates over 48 weeks.