Universität zu Köln

Ghofrani, Hossein-Ardeschir, Grimminger, Friedrich ORCID: 0000-0001-8725-6276, Gruenig, Ekkehard, Huang, Yigao, Jansa, Pavel ORCID: 0000-0002-3711-7064, Jing, Zhi-Cheng ORCID: 0000-0003-0493-0929, Kilpatrick, David, Langleben, David, Rosenkranz, Stephan, Menezes, Flavia, Fritsch, Arno, Nikkho, Sylvia and Humbert, Marc ORCID: 0000-0003-0703-2892 (2016). Predictors of long-term outcomes in patients treated with riociguat for pulmonary arterial hypertension: data from the PATENT-2 open-label, randomised, long-term extension trial. Lancet Resp. Med., 4 (5). S. 361 - 372. OXFORD: ELSEVIER SCI LTD. ISSN 2213-2600

Full text not available from this repository.

Abstract

Background Pulmonary arterial hypertension is a chronic disease associated with poor long-term outcomes. Identifying predictors of long-term outcome in pulmonary arterial hypertension is important to assess disease severity and guide treatment. We investigate associations between efficacy parameters and long-term outcomes in patients with pulmonary arterial hypertension receiving riociguat in the PATENT-2 study. We also present safety and efficacy data from the final data cutoff of PATENT-2, where most patients had received at least 2 years of riociguat treatment. Methods Eligible patients from the PATENT-1 study entered the PATENT-2 open-label extension, which will continue until all patients transition to the commercial drug. All patients received riociguat individually adjusted to a maximum dose of 2.5 mg three times a day. The primary endpoint was safety and tolerability, assessed with recording adverse events, serious adverse events, discontinuations, and deaths; exploratory assessments included 6-min walking distance (6MWD), WHO functional class, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentrations, Borg dyspnoea score, health-related quality of life (EQ-5D score), survival, and clinical worsening-free survival. Association between efficacy parameters and long-term outcomes was assessed using Kaplan-Meier analyses and a Cox proportional-hazards regression model. PATENT-2 is registered at ClinicalTrials.gov, number NCT00863681. Findings 396 patients entered PATENT-2, of whom 197 patients were receiving riociguat monotherapy and 199 were receiving riociguat in combination with endothelin receptor antagonists or prostanoids, or both. A significant association was noted between 6MWD, NT-proBNP concentration, and WHO functional class and overall survival at baseline (p=0.0006, 0.0225, and 0.0191, respectively), and at follow-up (p=0.021, 0.0056, and 0.0048, respectively). Riociguat was well tolerated in PATENT-2. Serious adverse events were recorded in 238 (60%) of the total population, and 45 (11%) patients discontinued treatment because of an adverse event. Improvements in 6MWD, WHO functional class, and NT-proBNP concentrations were maintained after 2 years of treatment. Interpretation These results support the long-term use of riociguat in patients with pulmonary arterial hypertension, and emphasise the prognostic value of 6MWD, WHO functional class, and NT-proBNP concentrations.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ghofrani, Hossein-Ardeschir UNSPECIFIED UNSPECIFIED UNSPECIFIED Grimminger, Friedrich UNSPECIFIED orcid.org/0000-0001-8725-6276 UNSPECIFIED Gruenig, Ekkehard UNSPECIFIED UNSPECIFIED UNSPECIFIED Huang, Yigao UNSPECIFIED UNSPECIFIED UNSPECIFIED Jansa, Pavel UNSPECIFIED orcid.org/0000-0002-3711-7064 UNSPECIFIED Jing, Zhi-Cheng UNSPECIFIED orcid.org/0000-0003-0493-0929 UNSPECIFIED Kilpatrick, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Langleben, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Rosenkranz, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Menezes, Flavia UNSPECIFIED UNSPECIFIED UNSPECIFIED Fritsch, Arno UNSPECIFIED UNSPECIFIED UNSPECIFIED Nikkho, Sylvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Humbert, Marc UNSPECIFIED orcid.org/0000-0003-0703-2892 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-277985
DOI:	10.1016/S2213-2600(16)30019-4
Journal or Publication Title:	Lancet Resp. Med.
Volume:	4
Number:	5
Page Range:	S. 361 - 372
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 6-MINUTE WALK DISTANCE; 1ST-LINE BOSENTAN; SUBCUTANEOUS TREPROSTINIL; PREVALENT COHORTS; SURVIVAL; THERAPY; METAANALYSIS; VALIDATION; INCIDENT Multiple languages Critical Care Medicine; Respiratory System Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27798