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Preliminary Experience With Bosentan as Initial Therapy in Childhood Idiopathic Pulmonary Arterial Hypertension

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Since September 2001, 7 consecutive patients with childhood idiopathic pulmonary arterial hypertension (IPAH), a rapidly progressive and fatal condition, have been treated with combinations of bosentan, and other therapies (sildenafil/warfarin/epoprostenol), at our institution. Survival and clinical status in these patients were compared with a group of 12 historic control patients who were diagnosed prior to 1997 and received only conventional medical therapy. Survival in the bosentan-treated subjects was better than among historic controls with comparable disease severity (log rank, p = 0.04). Our findings indicate treatment with bosentan permits a delay in IPAH disease progression and, in combination with other therapies, improves survival compared with historic control patients.

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Methods

The data from all children diagnosed with IPAH at The Royal Children’s Hospital, Melbourne, Australia, between January 1980 and February 2005, was retrospectively analyzed. Our institution provides the sole pediatric cardiology service for the state of Victoria, with a population of 4.5 million. For the purpose of this study, patients were divided into two groups—those receiving bosentan as primary therapy for IPAH (bosentan treatment group, n = 7) and those receiving conventional medical

Results

Table 1 shows the baseline demographics, initial cardiac catheter findings and outcomes in the two groups. Children in both the bosentan group and the historic control group were similar in terms of age, duration of symptoms and WHO classification. There were more females in the bosentan group and a higher proportion of familial cases compared with the historic control group (p = 0.027 and p = 0.014, respectively). The proportion of subjects with acute reactivity was similar in each group.

At

Discussion

We have shown that bosentan, when used as initial therapy in a small group of pediatric subjects with IPAH, is associated with improved survival compared with historic controls. These findings could not be explained by inclusion of more mildly affected cases or earlier diagnosis in the bosentan-treated subjects.

Endothelin-1 is a potent vasoconstrictor and smooth muscle cell mitogen, and plays an important role in the pathogenesis and evolution of pulmonary hypertension.19, 20 Plasma

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      However, the epoprostenol survival studies were performed mainly on patients in NYHA Class III at the time of inclusion in the study.5 Survival after IPAH diagnosis with and without prostanoid (and/or ERA) treatment has been intensively analyzed.1–7 Nevertheless, survival data on Tx lists for patients with pulmonary hypertension are scarce, especially for IPAH.8,9

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    Supported by a research scholarship (to C.M.S.) from The National Health and Medical Research Council, Australia (Grant 334394), and the Murdoch Children’s Research Institute, Melbourne, Australia.

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