Targeted oral therapies in the treatment of pulmonary arterial hypertension

Research output: Contribution to journalReview article

12 Scopus citations

Abstract

Recent advances in our understanding of the pathophysiology of pulmonary arterial hypertension (PAH) have led to the US FDAs 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.

Original languageEnglish (US)
Pages (from-to)811-826
Number of pages16
JournalClinical Drug Investigation
Volume30
Issue number12
DOIs
StatePublished - 2010

Keywords

  • Ambrisentan, therapeutic use
  • Bosentan, therapeutic use
  • Endothelin-receptor- antagonists, therapeutic use
  • Pulmonary-hypertension, treatment
  • Research-and-development
  • Sildenafil, therapeutic use
  • Tadalafil, therapeutic use
  • Type-5-cyclic-nucleotide-phosphodiesterase-inhibitors, therapeutic use.

ASJC Scopus subject areas

  • Pharmacology (medical)

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