‘Real-world’ ambrisentan data unveiled

Jun 11 2014

By Eleanor McDermid, Senior medwireNews Reporter

The use of and outcomes with ambrisentan in clinical practice are different to those in clinical trials, reflecting different patient characteristics in the “real world”, say researchers.

Robin Condliffe (Royal Hallamshire Hospital, Sheffield, UK) and colleagues analysed data on 272 patients treated with ambrisentan in a UK hospital between March 2009 and June 2013.

“There are relatively few data describing the long-term use of ambrisentan in a less strictly defined population more reflective of the ‘real world’,” the team comments in Therapeutic Advances in Respiratory Disease.

They found that ambrisentan was given as monotherapy in just 33.5% of patients, and only 11.8% received it first-line. This contrasts with the original randomised controlled trials of ambrisentan (ARIES-1 and 2), in which all patients received the drug as a first-line monotherapy.

However, the researchers say that this usage “reflects commissioning and prescribing practice in the UK whereby initial therapy for PAH is [phosphodiesterase-5 inhibitors] with subsequent addition or switch to other therapies if initial response is suboptimal.”

In addition, most patients in the ARIES trials had idiopathic PAH, or PAH associated with connective tissue disease, with a few having HIV or anorexigen use. But in this study, ambrisentan was also used to treat forms of PAH not studied in the clinical trials, including congenital heart disease, portopulmonary hypertension, respiratory disease and chronic thromboembolic disease.

In all, 18% of patients stopped treatment because of side effects. Just two (1%) patients discontinued because of abnormal liver function tests, but 20 (7%) did so because of oedema, a rate that the researchers say was 2–3 times higher than observed in the clinical trial population.

The next most common side effect leading to discontinuation was nausea, experienced by seven (3%) patients, followed by dyspnoea in four (1.5%) patients, then myalgia and rash, which each occurred in three (1%) patients.

“It was interesting to observe that 57% of patients stopping treatment in the current study also stopped other PAH therapies due to side effects”, say Condliffe et al. “This may reflect a lower symptom threshold in clinical practice or an increased difficulty in withdrawing medication in patients enrolled in clinical trials.”

Survival was again lower than in the clinical trial population, and varied according to PAH subtype. The 3-year survival rates were 80% for patients with congenital heart disease, 62% for those with idiopathic PAH and 38% for those with systemic sclerosis-associated PAH, which the researchers say “likely reflect differences in cardiac contractility and pulmonary vasculopathy between the groups.”

However, they note that patients who had improvements in World Health Organization functional class during treatment had the best survival, at about 80%, compared with 50% and 35% for patients with stable and worsening functional class, respectively.

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