Ambrisentan therapy in pulmonary hypertension: clinical use and tolerability in a referral centre.
Ambrisentan is an oral selective endothelin receptor antagonist licensed for use in pulmonary arterial hypertension (PAH). There are few data on clinical use and long-term tolerability in a wider range of patients with pulmonary hypertension (PH).



All patients treated with ambrisentan over a 4-year period were identified. Baseline characteristics, liver function test (LFT) results and World Health Organization (WHO) functional class were retrieved from hospital databases.



272 patients received ambrisentan between March 2009 and June 2013 (32% idiopathic PAH, 36% connective tissue disease PAH, 11% congenital heart disease PAH, 6% portopulmonary hypertension, 1% HIV PAH, 4% PH in association with lung disease, 8% chronic thromboembolic PH and 2% PH in association with sarcoidosis). 33.5% of patients received ambrisentan as monotherapy and 12% received ambrisentan as their initial PH therapy. 18% stopped treatment due to side effects and 12% stopped due to lack of efficacy. Oedema was the most common side effect leading to cessation of therapy, which occurred in 7% of patients. 57% of patients who discontinued ambrisentan due to side effects also discontinued other PAH therapies due to side effects previously or subsequently. Ambrisentan was discontinued in two (<1%) patients due to abnormal LFTs. The 3-year survival in congenital heart disease PAH, idiopathic PAH and systemic sclerosis-associated PAH was 80%, 62%, and 38%, respectively (p = 0.003). Survival was superior in patients in whom WHO functional class improved in response to therapy.



Ambrisentan is used as an initial therapy and as monotherapy in a minority of patients in a large UK PH referral centre. Discontinuation due to side effects, and especially oedema, was higher than reported in previous studies while discontinuation due to abnormal LFTs was very uncommon. A majority of patients who discontinued therapy due to side effects also previously or subsequently discontinued other PAH therapies. Improvement in WHO functional class was associated with superior survival.
Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield S10 2JF, UK robin.condliffe@sth.nhs.uk.
Robin
R
Condliffe
Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK.
Charlie A
CA
Elliot
Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK.
Judith
J
Hurdman
Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital and Department of Infection and Immunity, University of Sheffield, Sheffield, UK.
Ian
I
Sabroe
Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK.
Catherine
C
Billings
Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK.
David G
DG
Kiely
Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK.
Neil
N
Hamilton
ambrisentan; liver function tests; pulmonary hypertension; side effects