Sildenafil improves renal function in patients with pulmonary arterial hypertension.
OBJECTIVE
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 post hoc analysis assessed the effect of sildenafil on kidney function and links with clinical outcomes including 6-min walk distance, functional class, time to clinical worsening and survival.


METHODS
Patients with PAH received placebo or sildenafil 20, 40 or 80 mg three times daily in the SUPER-1 study and open-label sildenafil titrated to 80 mg three times daily (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 < 0.05). In patients who maintained or improved kidney function, time to worsening was significantly delayed (P < 0.02 for both kidney parameters). Observed trends towards improved survival were not significant. Patients with eGFR <60 (vs. ≥60) ml min(-1) 1.73 m(-2) appeared to have worse survival.


CONCLUSIONS
Sildenafil treatment was associated with improved kidney function in patients with PAH, which was in turn associated with improved exercise capacity and functional class, a reduced risk of clinical worsening, and a trend towards reduced mortality.
Christison Professor of Therapeutics and Clinical Pharmacology, Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
David J
DJ
Webb
Departement de Cardiologie, CUB-Hôpital Erasme, Brussels, Belgium.
Jean-Luc
JL
Vachiery
Director, Clinical Statistics, Specialty Care Business Unit, Pfizer Inc, New York, NY, USA.
Lie-Ju
LJ
Hwang
Inflammation Field Medical Director/Director US Medical Affairs, Pfizer Inc, New York, NY, USA.
Julie O
JO
Maurey
D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D011379:Prognosis; D000068677:Sildenafil Citrate / Q000008:administration & dosage / Q000627:therapeutic use*; D064804:Urological Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D064804:Urological Agents; D003404:Creatinine; D000068677:Sildenafil Citrate
creatinine; glomerular filtration rate; kidney; outcomes; sildenafil