Vitamin D deficiency, a potential cause for insufficient response to sildenafil in pulmonary arterial hypertension.

Phosphodiesterase 5 (PDE5) inhibitors (PDE5i), such as sildenafil and tadalafil, are frequently used to treat pulmonary arterial hypertension (PAH) [1]. Combined therapy of PDE5i with drugs acting via other signaling mechanisms, i.e. , the endothelin pathway, is currently recommended as it provides better clinical outcomes than monotherapy with PDE5i [1, 2]. The soluble guanylyl cyclase (sGC) stimulator riociguat is an interesting alternative to PDE5i with a different mode of action but on the same signaling pathway. Recently, the results of the REPLACE study show that, in patients remaining at intermediate risk of 1-year mortality after PDE5i treatment, switching to riociguat is beneficial in terms of clinical improvement and risk status as compared with PDE5i maintenance therapy [3]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Competing interest: Joan Albert Barbera has received grants and honoraria from Actelion, Janssen, MSD and GSK. Competing interest: Isabel Blanco has received honoraria from Actelion, Janssen and MSD. Competing interest: Francisco Perez-Vizcaino has received a lecture fee from Actelion. Competing interest: Maria Callejo has no competing interests.