Sildenafil Improves Renal Function in Patients With Pulmonary Arterial Hypertension
David J. Webb, MD,1 Jean-Luc Vachiery, MD,2 Lie-Ju Hwang, PhD,3 Julie O. Maurey, PharmD4 1
Christison Professor of Therapeutics and Clinical Pharmacology, Centre for
Cardiovascular Science, University of Edinburgh, Edinburgh, UK; 2Departement de Cardiologie, CUB-Hôpital Erasme, Brussels, Belgium; 3Director, Clinical Statistics, Specialty Care Business Unit, Pfizer Inc, New York, NY, USA; 4 Inflammation Field Medical Director/Director US Medical Affairs, Pfizer Inc, New York, NY, USA
Address correspondence/reprint requests to: Professor David Webb Address: Room E3.22, Clinical Pharmacology Unit BHF Centre of Research Excellence (CoRE) Queen's Medical Research Institute, 47 Little France Crescent Edinburgh EH16 4TJ Scotland, UK Telephone: +44 131 242 9215 E-mail: [email protected] Running head: Sildenafil, Kidney Function, and Outcomes Keyword(s): sildenafil, creatinine, glomerular filtration rate, kidney, outcomes Word count (excluding title page, summary, references, tables, and figures): 1890 Number of tables and figures: 6
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bcp.12616
This article is protected by copyright. All rights reserved.
Summary Aim: Elevated serum creatinine (SCr) and low estimated glomerular filtration rate (eGFR) are associated with poor outcomes in patients with pulmonary arterial hypertension (PAH) whereas sildenafil treatment improves PAH outcomes. This posthoc analysis assessed the effect of sildenafil on kidney function and links with clinical outcomes including 6-minute walk distance, functional class, time to clinical worsening, and survival. Methods: Patients with PAH received placebo or sildenafil 20, 40, or 80 mg TID in the SUPER-1 study and open-label sildenafil titrated to 80 mg TID (as tolerated) in the extension study. Results: Baseline characteristics were similar among groups (N=277); PAH was mostly idiopathic (63%) and functional class II (39%) or III (58%). From baseline to week 12, kidney function improved (increased eGFR, decreased SCr) with sildenafil and worsened with placebo. In univariate logistic regression, improved kidney function was associated with significantly improved exercise and functional class (odds ratios, 1.17 [95% CI, 1.01–1.36] and 1.21 [95% CI, 1.03–1.41], respectively, for SCr; and 0.97 [95% CI, 0.94–0.99] and 0.97 [95% CI, 0.94–0.99] for eGFR; all P
David J. Webb, MD,1 Jean-Luc Vachiery, MD,2 Lie-Ju Hwang, PhD,3 Julie O. Maurey, PharmD4 1
Christison Professor of Therapeutics and Clinical Pharmacology, Centre for
Cardiovascular Science, University of Edinburgh, Edinburgh, UK; 2Departement de Cardiologie, CUB-Hôpital Erasme, Brussels, Belgium; 3Director, Clinical Statistics, Specialty Care Business Unit, Pfizer Inc, New York, NY, USA; 4 Inflammation Field Medical Director/Director US Medical Affairs, Pfizer Inc, New York, NY, USA
Address correspondence/reprint requests to: Professor David Webb Address: Room E3.22, Clinical Pharmacology Unit BHF Centre of Research Excellence (CoRE) Queen's Medical Research Institute, 47 Little France Crescent Edinburgh EH16 4TJ Scotland, UK Telephone: +44 131 242 9215 E-mail: [email protected] Running head: Sildenafil, Kidney Function, and Outcomes Keyword(s): sildenafil, creatinine, glomerular filtration rate, kidney, outcomes Word count (excluding title page, summary, references, tables, and figures): 1890 Number of tables and figures: 6
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bcp.12616
This article is protected by copyright. All rights reserved.
Summary Aim: Elevated serum creatinine (SCr) and low estimated glomerular filtration rate (eGFR) are associated with poor outcomes in patients with pulmonary arterial hypertension (PAH) whereas sildenafil treatment improves PAH outcomes. This posthoc analysis assessed the effect of sildenafil on kidney function and links with clinical outcomes including 6-minute walk distance, functional class, time to clinical worsening, and survival. Methods: Patients with PAH received placebo or sildenafil 20, 40, or 80 mg TID in the SUPER-1 study and open-label sildenafil titrated to 80 mg TID (as tolerated) in the extension study. Results: Baseline characteristics were similar among groups (N=277); PAH was mostly idiopathic (63%) and functional class II (39%) or III (58%). From baseline to week 12, kidney function improved (increased eGFR, decreased SCr) with sildenafil and worsened with placebo. In univariate logistic regression, improved kidney function was associated with significantly improved exercise and functional class (odds ratios, 1.17 [95% CI, 1.01–1.36] and 1.21 [95% CI, 1.03–1.41], respectively, for SCr; and 0.97 [95% CI, 0.94–0.99] and 0.97 [95% CI, 0.94–0.99] for eGFR; all P
