The Role of Oral Vasoactive Agents in the Treatment of Pulmonary Arterial Hypertension

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US Cardiology, 2006;3(1):1-5

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Pulmonary arterial hypertension (PAH) is a disorder of the pulmonary circulation in which elevated pressure in the pulmonary vascular circuit, when severe, can lead to right heart failure and eventually cause death. The last three decades have seen significant advances in our understanding of this group of disorders and, with this understanding, the development of novel therapies to assist in their treatment. A successful and comprehensive approach to the diagnosis and treatment of this complex and rapidly progressive disease requires a collaboration between the patient, the resources at the pulmonary hypertension center, and the resources at the community level.1 The treatment options for patients with PAH have expanded greatly in the recent past, with novel therapies now available and others on the way.2

This article will outline the oral agents available or undergoing trials (see Table 1) for PAH therapy and will summarize the evidence regarding the role of oral agents in treating these patients.

Calcium-channel Blockers

In view of the proven efficacy of newer therapies, it is now recommended that calcium-channel blockers (CCBs) should only be used in patients with demonstrated vasoreactivity and never be used to empirically treat PAH. Patients demonstrating vasoreactivity, initiated on CCBs alone, should be followed very closely for signs of progressive disease, since approximately 50% of these patients will experience deterioration over time, necessitating the addition of newer forms of therapy.3

Endothelin Antagonists

Endothelin-1 (ET-1) is a potent vasoconstrictor and a mediator of the pulmonary vascular remodeling seen in PAH.4 Two receptors for ET-1 have been identified, ETA and ETB, with the former mediating vasoconstriction and remodeling and the latter involved in the clearance of ET-1 and perhaps also in vasodilatation and nitric oxide (NO) release. Many ET receptor antagonists, including sitaxsentan and ambrisentan, are being studied in PH; however, only bosentan is currently available for use in the US.

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