Echocardiographic findings in pulmonary arterial hypertension (PAH) include enlargement, hypertrophy and decreased contraction of the right ventricle. Echocardiographic assessment of patients receiving long-term PAH treatment is limited.Treprostinil, a stable prostacyclin analog administered as a continuous subcutaneous infusion, diminished the symptoms of PAH in 12-week clinical efficacy studies. Echocardiography studies in PAH patients receiving long-term treprostinil treatment (beyond 3 months) may identify the effects of this compound on right ventricular performance.
Long-term efficacy was evaluated in a cohort of patients receiving treprostinil as primary therapy for moderate to severe PAH. Doses of treprostinil were adjusted during the study to reduce symptoms of PAH without producing intolerable adverse effects. Echocardiographic studies, 6-minute walk tests and WHO functional classification were performed pre-treatment and upon achievement of the optimal therapeutic dose.
Ten patients (9 female/1 male) received subcutaneous treprostinil for an average duration of 17 months (range: 9–30 months). Mean age (±SD) was 55.0±13.0 years. Pretreatment WHO functional class was: class IV (n=5), class III (n=4) and class II (n=1). Right ventricular systolic pressure (RVSP) ranged from 64 to 110 mmHg (mean±SD, 81±15 mmHg). Right ventricular ejection fraction (RVEF) ranged from 10 to 35 percent (mean±SD, 27±9 percent). Baseline assessment of right ventricular hypertrophy (RVH) was moderate (n=6) to severe (n=4).The mean dose of treprostinil at the follow-up assessment was 29.8±10.6 ng/kg/min. Mean RVSP decreased from 81 mmHg to 60 mmHg (p<0.001). Mean RVEF increased from 27 percent to 41 percent (p<0.001). Follow-up assessment of RVH was mild (n=2) to moderate (n=8). All patients reported improved symptoms and had WHO functional class improvement. Exercise capacity improved with mean distance walked in six minutes increasing by 59 meters (p<0.05).CONCLUSIONS: Long-term treatment with treprostinil improves the echocardiographic manifestations of PAH as well as the clinical symptoms and exercise capacity.
Subcutaneous treprostinil is a promising alternative to intravenous epoprostenol for the long-term treatment of patients with moderate to severe PAH.
D. Zwicke, United Therapeutics. Clinical Trials Grant