Support for upfront combination therapy in scleroderma-associated PAH
medwireNews: Upfront therapy with ambrisentan and tadalafil may help patients with scleroderma-associated pulmonary arterial hypertension (SSc-PAH), research suggests.
Paul Hassoun (Johns Hopkins University, Baltimore, Maryland, USA) and co-workers trialled the combination therapy in 24 treatment-naïve SSc-PAH patients, noting that they are “notoriously less responsive to modern PAH therapy compared to [idiopathic] PAH patients in large series”.
The patients received ambrisentan 5 mg/day and tadalafil 20 mg/day for the first 4 weeks, after which the doses were up-titrated to 10 mg/day and 40 mg/day, respectively.
During 36 weeks of treatment, the patients achieved a significant 55% reduction in pulmonary vascular resistance (PVR), from a median of 6.9 to 3.1 Wood Units, with all patients having at least a 20% reduction. Also, right ventricular (RV) mass decreased by a significant 14%, from a median of 32.5 to 28.0 g, although not all patients benefitted, with 15 having at least a 10% decrease, five having no change and three an increase.
The researchers chose to measure PVR and RV mass rather than 6-minute walk distance, because the validity of the latter has been questioned in SSc-PAH patients “considering they are often heavily burdened with musculoskeletal impairment.”
The team says that this “compares very favorably” with the average improvements obtained in mixed populations of PAH patients treated in randomised controlled trials, and in SSc-PAH patients given a continuous intravenous infusion of prostacyclin.
But “such comparisons should be interpreted with caution considering the lack of a comparator control group in our study”, they write in the American Journal of Respiratory and Critical Care Medicine.
However, the researchers note that the findings are in line with those from the recently published randomised, controlled AMBITION trial, which found upfront combination therapy to be effective in PAH patients, including more than a third with connective tissue disease.
Patients in the current study also had significant improvements in other haemodynamic variables, including mean pulmonary arterial pressure, right atrial pressure, cardiac output and the ratio of stroke volume to pulmonary pulse pressure.
In addition, their serum N-terminal pro-brain natriuretic peptide levels halved, on average, and they reported significant improvement in health-related quality of life, particularly in the physical functioning, vitality and mental health domains.
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