Evidence for the use of combination targeted therapeutic approaches for the management of pulmonary arterial hypertension.
The last decade has witnessed a remarkable increase in the number of effective treatment options available for the management of patients with pulmonary arterial hypertension. In this regard, agents belonging to the therapeutic classes that specifically target the prostacyclin, endothelin and nitric oxide pathways have shown the greatest efficacy in clinical studies to date. These various drug treatments have individually been shown to confer improvements in symptoms, exercise capacity, pulmonary haemodynamics and possibly survival in different patient subgroups. However, pulmonary arterial hypertension is characterised by dysregulation of a variety of pathways. In addition, disease worsening is inevitable for the majority of patients receiving monotherapy. As a consequence, there is increasing interest in the use of treatment combinations in order to target multiple targets with the aim of restoring normal pulmonary vascular function in order to improve clinical status. Indeed, use of multiple specific-treatment regimens is now part of routine clinical practice and is emphasized in recently published therapeutic guidelines. This review details the rationale for the different combination strategies and examines the clinical evidence in favour of some of the approaches that have been evaluated.
O'Callaghan
Dermot S
DS
Université Paris-Sud, Faculté de Médecine, Kremlin-Bicêtre F-94276, France. dsocallaghan@yahoo.com
Savale
Laurent
L
Jaïs
Xavier
X
Natali
Delphine
D
Montani
David
D
Humbert
Marc
M
Simonneau
Gérald
G
Sitbon
Olivier
O
D000959:Antihypertensive Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D065128:Endothelin Receptor Antagonists; D011464:Epoprostenol / Q000008:administration & dosage; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D017466:Receptors, Endothelin / Q000008:administration & dosage; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D017466:Receptors, Endothelin; D009569:Nitric Oxide; D011464:Epoprostenol