Ambrisentan use for pulmonary arterial hypertension in a post-authorization drug registry: The VOLibris Tracking Study.
BACKGROUND
The VOLibris Tracking (VOLT) Study was an open-label, prospective, observational, multicenter, post-marketing registry program designed to more fully characterize the safety profile of ambrisentan for the treatment of pulmonary arterial hypertension (PAH). The key outcome was the incidence of aminotransferase elevations >3× the upper limit of normal (ULN).


METHODS
In total, 999 patients from 115 centers in 15 countries, who were prescribed ambrisentan for the treatment of PAH (Functional Class II and III) between 30 June 2008 and 13 May 2011, were enrolled. Of these, 238 had PAH associated with connective tissue disease (PAH-CTD) and 220 had no prior PAH-specific therapy. Routine clinical monitoring data were collected by physicians.


RESULTS
The incidence of both alanine and aspartate aminotransferase events (>3× ULN) was 0.02 per patient-year (95% confidence interval 0.015 to 0.027). Similar results were reported for the PAH-CTD and PAH-specific-therapy-naive subgroups. Overall, 514 (52%) patients reported treatment-emergent adverse events of special interest, most commonly edema/fluid retention (249, or 25%) and anemia (143, or 14%).


CONCLUSIONS
Data from the VOLT study indicate no new ambrisentan-related safety signals. Ambrisentan was not associated with increases in liver function test abnormalities above the assumed background incidence of 1.5% per year, and the observed safety profile of ambrisentan was consistent with previously published data.
Pulmonary Vascular Diseases Unit, Hôpital Erasme, Cliniques Universitaires De Bruxelles, Bruxelles, Belgium. Electronic address: jeanluc.vachiery@erasme.ulb.ac.be.
Jean-Luc
JL
Vachiéry
Department of Respiratory Medicine, Hannover Medical School and German Centre of Lung Research, Hannover, Germany.
Marius M
MM
Hoeper
Scottish Pulmonary Vascular Unit, Regional Heart and Lung Centre, Golden Jubilee National Hospital and University of Glasgow, Glasgow, UK.
Andrew J
AJ
Peacock
Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, INSERM UMR-S 999, APHP, service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
Olivier
O
Sitbon
Cardiology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Martino
M
Cheli
Scottish Pulmonary Vascular Unit, Regional Heart and Lung Centre, Golden Jubilee National Hospital and University of Glasgow, Glasgow, UK.
Colin
C
Church
Department of Respiratory Medicine, Hannover Medical School and German Centre of Lung Research, Hannover, Germany.
Karen M
KM
Olsson
Department of Experimental, Diagnostic and Specialty Medicine, Bologna University Hospital, Bologna, Italy.
Massimiliano
M
Palazzini
GlaxoSmithKline, Philadelphia, Pennsylvania, USA.
Brian
B
Waterhouse
GlaxoSmithKline, Brentford, Middlesex, UK.
Jonathan
J
Langley
Department of Experimental, Diagnostic and Specialty Medicine, Bologna University Hospital, Bologna, Italy.
Nazzareno
N
Galié
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D005260:Female; D006760:Hospitalization; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D010666:Phenylpropionates / Q000627:therapeutic use*; D011358:Product Surveillance, Postmarketing; D011446:Prospective Studies; D011724:Pyridazines / Q000627:therapeutic use*; D012042:Registries; D000637:Transaminases / Q000097:blood; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D010666:Phenylpropionates; D011724:Pyridazines; D000637:Transaminases; C467894:ambrisentan
ambrisentan; post-authorisation safety study; pulmonary arterial hypertension; registry; safety