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Sildenafil improves renal function in patients with pulmonary arterial hypertension
Author(s) -
Webb David J.,
Vachiery JeanLuc,
Hwang LieJu,
Maurey Julie O.
Publication year - 2015
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12616
Subject(s) - sildenafil , medicine , renal function , urology , placebo , creatinine , odds ratio , kidney disease , cardiology , pathology , alternative medicine
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 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.