title: Acute effects of riociguat in borderline or manifest pulmonary hypertension associated with chronic obstructive pulmonary disease.
abstract: Riociguat is the first oral soluble guanylate cyclase stimulator shown to improve pulmonary hemodynamics in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (PH). This pilot study assessed the impact of a single dose of riociguat on hemodynamics, gas exchange, and lung function in patients with PH associated with chronic obstructive pulmonary disease (COPD). Adults with COPD-associated borderline or manifest PH (pulmonary vascular resistance > 270 dyn·s·cm(-5), mean pulmonary artery pressure ≥ 23 mmHg, ratio of forced expiratory volume in 1 second [FEV1] to forced vital capacity < 70%, and partial pressure of oxygen and carbon dioxide in arterial blood > 50 and ≤ 55 mmHg, respectively) received riociguat 1 or 2.5 mg during right heart catheterization. Twenty-two patients completed the study (11 men, 11 women, aged 56-82 years; 1-mg group: n = 10 [mean FEV1: 43.1%]; 2.5-mg group: n = 12 [mean FEV1: 41.2%]). Riociguat caused significant improvements (P < 0.01) from baseline in mean pulmonary artery pressure (1 mg: -3.60 mmHg [-11.44%]; 2.5 mg: -4.83 mmHg [-14.76%]) and pulmonary vascular resistance (1 mg: -58.32 dyn·s·cm(-5) [-15.35%]; 2.5 mg: -123.8 dyn·s·cm(-5) [-32.96%]). No relevant changes in lung function or gas exchange were observed. Single doses of riociguat were well tolerated and showed promising hemodynamic effects without untoward effects on gas exchange or lung function in patients with COPD-associated PH. Placebo-controlled studies of chronic treatment with riociguat are warranted.
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: Hossein A
authors.initials: HA
authors.lastname: Ghofrani
authors.affiliation: Medical Clinic I, Pneumology, Loewenstein Clinic, Loewenstein, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Staehler
authors.affiliation: Thorax Clinic, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Grünig
authors.affiliation: Medical Clinic 1/Pneumology, University Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Halank
authors.affiliation: Kerckhoff-Klinik, Bad Nauheim, Germany.
authors.forename: Veselin
authors.initials: V
authors.lastname: Mitrovic
authors.affiliation: Global Biostatistics, Pharma Research Center, Bayer Pharma, Wuppertal, Germany.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Unger
authors.affiliation: Clinical Pharmacology, Pharma Research Center, Bayer Pharma, Wuppertal, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Mueck
authors.affiliation: Clinical Pharmacology, Pharma Research Center, Bayer Pharma, Wuppertal, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Frey
authors.affiliation: Universities of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
authors.affiliation: Pulmonary Pharmacotherapy, UGMLC, Giessen, Germany.
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Schermuly
authors.affiliation: Department of Internal Medicine V, University of Munich, and Asklepios Lung Center Munich-Gauting, Comprehensive Pneumology Center, member of the DZL, Munich, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Behr
keywords: clinical trial; hemodynamics; multiple inert-gas elimination technique; pulmonary gas exchange; soluble guanylate cyclase