Universität zu Köln

Hoeper, Marius M., McLaughlin, Vallerie V., Albert Barbera, Joan, Frost, Adaani E., Ghofrani, Hossein-Ardeschir, Peacock, Andrew J., Simonneau, Gerald, Rosenkranz, Stephan, Oudiz, Ronald J., White, R. James, Miller, Karen L., Langley, Jonathan, Harris, Julia H. N., Blair, Christiana, Rubin, Lewis J. and Vachiery, Jean-Luc (2016). Initial combination therapy with ambrisentan and tadalafil and mortality in patients with pulmonary arterial hypertension: a secondary analysis of the results from the randomised, controlled AMBITION study. Lancet Resp. Med., 4 (11). S. 894 - 902. OXFORD: ELSEVIER SCI LTD. ISSN 2213-2600

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Abstract

Background In treatment-naive patients with pulmonary arterial hypertension, initial combination therapy with ambrisentan and tadalafil reduces the risk of clinical failure events compared with monotherapy. We did this secondary analysis to further investigate the effect of combination therapy on survival. Methods We analysed survival data from the modified intention-to-treat population of the Ambrisentan and Tadalafil in Patients with Pulmonary Arterial Hypertension (AMBITION) trial. AMBITION was a multicentre, randomised, double-blind study, in which treatment-naive patients with pulmonary arterial hypertension were randomly assigned in a 2:1:1 ratio and received combination therapy with ambrisentan and tadalafil, ambrisentan and placebo, or tadalafil and placebo. We did a prespecified analysis of all mortality events from randomisation to the end of the study, including patients who discontinued their assigned treatment. In a post-hoc analysis, we analysed survival at 7 days after the termination of each individual patient's randomised treatment. We used Cox proportional hazard regression, Kaplan-Meier survival estimates, and the stratified log-rank test to compare the survival of patients receiving initial combination therapy or initial monotherapy. Findings The study population consisted of 605 patients with pulmonary arterial hypertension who were randomly assigned and received combination therapy (n=302) or monotherapy (n=303; 152 patients assigned to ambrisentan monotherapy and 151 patients to tadalafil monotherapy). At the end of the study, 29 (10%) of 302 patients in the combination therapy group had died compared with 41 (14%) of 303 patients in the monotherapy group (hazard ratio 0.67, 95% CI 0.42-1.08; stratified log-rank p=0.10). At 7 days after the end of randomised treatment, fewer patients had died in the combination therapy group (3 [1%] of 302 patients) compared with the monotherapy group (13 [4%] of 303 patients; hazard ratio 0.21, 95% CI 0.06-0.73). Interpretation These data indicate that initial combination therapy might be associated with a survival advantage compared with initial monotherapy in patients with newly diagnosed pulmonary arterial hypertension. This hypothesis needs to be addressed in future studies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hoeper, Marius M. UNSPECIFIED UNSPECIFIED UNSPECIFIED McLaughlin, Vallerie V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Albert Barbera, Joan UNSPECIFIED UNSPECIFIED UNSPECIFIED Frost, Adaani E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ghofrani, Hossein-Ardeschir UNSPECIFIED UNSPECIFIED UNSPECIFIED Peacock, Andrew J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Simonneau, Gerald UNSPECIFIED UNSPECIFIED UNSPECIFIED Rosenkranz, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Oudiz, Ronald J. UNSPECIFIED UNSPECIFIED UNSPECIFIED White, R. James UNSPECIFIED UNSPECIFIED UNSPECIFIED Miller, Karen L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Langley, Jonathan UNSPECIFIED UNSPECIFIED UNSPECIFIED Harris, Julia H. N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Blair, Christiana UNSPECIFIED UNSPECIFIED UNSPECIFIED Rubin, Lewis J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vachiery, Jean-Luc UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-257149
DOI:	10.1016/S2213-2600(16)30307-1
Journal or Publication Title:	Lancet Resp. Med.
Volume:	4
Number:	11
Page Range:	S. 894 - 902
Date:	2016
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	2213-2600
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language 2015 ESC/ERS GUIDELINES; DIAGNOSIS; MONOTHERAPY Multiple languages Critical Care Medicine; Respiratory System Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25714