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This Article Full Text Full Text (PDF) All Versions of this Article: 0091270009341182v1 49/11/1343    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Google Scholar Articles by Gruenig, E. Articles by Galiè, N. PubMed PubMed Citation Articles by Gruenig, E. Articles by Galiè, N. Social Bookmarking                         What's this?

Acute Hemodynamic Effects of Single-Dose Sildenafil When Added to Established Bosentan Therapy in Patients With Pulmonary Arterial Hypertension: Results of the COMPASS-1 Study

From University Hospital, Heidelberg, Germany (Dr Gruenig, Dr Meyer); University of Alberta Hospital, Alberta, Canada (Dr Michelakis); ULB-Erasme University Hospital, Brussels, Belgium (Dr Vachiéry); University La Sapienza, Rome, Italy (Dr Vizza); Actelion Pharmaceuticals, Allschwil, Switzerland (Dr Doelberg, Dr Bach, Dr Dingemanse); and University of Bologna, Bologna, Italy (Dr Galiè). The study was supported by Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.

This study investigated the acute pharmacodynamic effects of sildenafil in patients with pulmonary arterial hypertension (PAH) and concomitant bosentan treatment, in view of a mutual pharmacokinetic interaction between the 2 drugs. This prospective, open-label, noncomparative, multicenter, phase II study enrolled 45 patients (18 years) with stable PAH (idiopathic, familial, or related to corrected congenital systemic-to-pulmonary shunts, drugs, or toxins) and on bosentan treatment for at least 3 months. Patients underwent right heart catheterization to evaluate the acute hemodynamic effects of (a) inhaled nitric oxide (iNO) and (b) a single oral dose of sildenafil (25 mg). Mean pulmonary vascular resistance (PVR) decreased from baseline following iNO (-15%; 95% confidence limits: -21%, -8%; P = .0001). A statistically significant decrease from baseline in mean PVR was also observed 60 minutes following sildenafil administration (-15%; 95% confidence limits: -21%, -10%; P < .0001). The reduction in PVR following sildenafil was comparable to that resulting from iNO. There were no unexpected safety findings. The pharmacodynamic effect suggests that addition of sildenafil to bosentan treatment can elicit additional hemodynamic benefits. These data represent a rationale for long-term combination studies with the 2 compounds.

Key Words: Pulmonary arterial hypertension • bosentan • sildenafil • pharmacodynamics

Address for reprints: Ekkehard Gruenig, MD, Thoraxklinik am Universitätsklinikum Heidelberg, Amalienstrasse 5, 69126 Heidelberg, Germany; e-mail: ekkehard.gruenig{at}thoraxklinik-heidelberg.de.

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