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© 2009 the European Respiratory Society
The use of combination therapy in pulmonary arterial hypertension: new developments
* Institute of Cardiology, University of Bologna, Bologna, Italy. # Hôpital Antoine Béclère, Université Paris-Sud, Clamart, France.
CORRESPONDENCE: N. Galiè, Institute of Cardiology, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. E-mail: nazzareno-galie{at}unibo.it
Received: June 11, 2009
Accepted June 24, 2009
ABSTRACT
There is a strong clinical rationale for combination therapy in pulmonary arterial hypertension (PAH), as several pathological pathways have been implicated in its pathogenesis and no single agent has yet been shown to deliver completely satisfactory results. Registry data indicate that use of combination therapy is in fact common in existing clinical practice, even though support has been largely empirical or derived from small-scale observational studies. Data from large, adequately powered, randomised controlled trials of combination therapy in PAH are now emerging and suggest that combination therapy may be clinically beneficial. Studies of bosentan in combination with prostanoids and phosphodiesterase (PDE)-5 inhibitors show consistent evidence of improvements in exercise capacity compared with placebo. Similar improvements have been observed with PDE-5 inhibitors in combination with prostanoids. The appropriate timing of combination therapy requires further evaluation but goal-oriented therapy using combinations of oral and inhaled drugs has been shown to provide acceptable long-term results in patients with advanced PAH. Monitoring should be performed regularly and be based on repeatable, noninvasive, measurable parameters that have prognostic value.
KEYWORDS: Combination therapy, endothelin receptor antagonists, phosphodiesterase type-5 inhibitors, prostanoids, pulmonary arterial hypertension
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