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Targeted Oral Therapies in the Treatment of Pulmonary Arterial Hypertension

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Abstract

Recent advances in our understanding of the pathophysiology of pulmonary arterial hypertension (PAH) have led to the US FDA’s approval of eight drugs for its treatment. Although guidelines for the use of PAH therapies are available and regularly updated, there is a lack of information on how these agents differ and what characteristics may enable one agent to be of greater relative clinical utility than another. Oral agents may be compared across a variety of measures, including clinical efficacy, safety and tolerability, dosing and pharmacology, potential for drug interactions, treatment adherence and suitability for use in combination regimens. Although no large, prospective, head-to-head trial has been conducted with oral agents for PAH, data from placebo-controlled studies indicate that the enrolled patient populations were remarkably homogeneous with respect to demographic and disease severity parameters. In general, data suggest that these agents improve functional capacity, delay disease progression and improve haemodynamics. Additionally, long-term sustainability of response has been demonstrated. However, there was no consistently superior agent across the primary and secondary endpoints assessed in these trials, and the magnitudes of improvements were in a fairly defined range across agents. Consequently, treatment choice may shift to other aspects such as drug safety and tolerability, potential for drug interactions, dosing convenience, treatment adherence, effect on quality of life and access to medication. In this review, the four targeted oral agents approved for the treatment of PAH in the US are reviewed, and clinical results are placed into context.

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Acknowledgements

Editorial assistance was provided under the direction of the author by MedThink Communications, Inc., with support from United Therapeutics Corporation. Dr Safdar has received consultancy fees and honoraria from United Therapeutics, Actelion Pharmaceuticals Ltd, and Gilead Sciences, Inc., and has stock ownership options of less than $US5000.00 for Gilead Sciences, Encysive Pharmaceuticals Inc., and United Therapeutics. Dr Safdar did not receive any funding for the preparation of this review article. The decision to submit this manuscript to Clinical Drug Investigation was made by Dr Safdar.

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  1. Division of Pulmonary-Critical Care Medicine, Baylor College of Medicine, Houston, Texas, USA

    Zeenat Safdar

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Safdar, Z. Targeted Oral Therapies in the Treatment of Pulmonary Arterial Hypertension. Clin. Drug Investig. 30, 811–826 (2010). https://doi.org/10.2165/11538870-000000000-00000

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