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Uric acid and other renal function parameters in patients with stable angina pectoris participating in the ACTION trial: impact of nifedipine GITS (gastro-intestinal therapeutic system) and relation to outcome

Ruilope, Luis Ma; Kirwan, Bridget-Anneb; de Brouwer, Sophieb; Danchin, Nicolasc; Fox, Keith AAd; Wagener, Gilberte; Segura, Juliana; Poole-Wilson, Philip Af; Lubsen, Jacobusb,gon behalf of the ACTION investigators

doi: 10.1097/HJH.0b013e3281c49d93
Original papers: Kidney
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Background Little data is available concerning the prognostic implications of renal function abnormalities, their evolution over time and the effects of nifedipine on such abnormalities in patients with stable angina pectoris.

Methods The previously published ACTION trial compared long-acting nifedipine GITS 60 mg once daily to placebo among 7665 patients. Standard laboratory tests including creatinine and uric acid were assessed at baseline, after 6 months, 2 and 4 years, and at the end of follow-up. We assessed the impact of nifedipine on markers of renal dysfunction and determined whether evidence of renal failure alters the impact of nifedipine on the clinical outcome of patients with stable angina.

Results Uric acid was not while creatinine level and estimated creatinine clearance were potent conditionally independent predictors of total mortality and of cardiovascular clinical events. Relative to placebo, nifedipine reduced 6-month uric acid levels by 3% (P < 0.001) of the baseline value. This difference was maintained during long-term follow-up, was present both in normotensives and in hypertensives, and was not explained by differences in diuretic therapy or allopurinol use. Nifedipine had no effect on the occurrence of clinical renal failure. Relative to placebo, the effects of nifedipine on cardiovascular death or myocardial infarction [hazard ratio (HR) = 1.01, 95% confidence interval (CI) 0.88–1.17], any stroke or transient ischaemic attack (HR = 0.73, 95% CI 0.60–0.88), new overt heart failure (HR = 0.72, 95% CI 0.55–0.95), and the need for any coronary procedure (HR = 0.81, 95% CI 0.75–0.88) were consistent across strata of markers of renal dysfunction.

Conclusions We conclude that, in patients with stable angina, nifedipine reduces uric acid levels and does not affect other markers of renal dysfunction. Renal dysfunction does not alter the effects of nifedipine on clinical outcome.

aHypertension Unit, Hospital 12 de Octubre. Madrid, Spain

bSOCAR Research, Nyon, Switzerland

cDepartment of Cardiology, Georges Pompidou European Hospital, Paris, France

dCardiovascular Research, Division of Medical & Radiological Sciences, The University of Edinburgh, UK

eD-659423 Unna, Germany

fCardiac Medicine, Imperial College, London, UK

gDepartment of Epidemiology and Biostatistics, Erasmus Medical Centre, Rotterdam, The Netherlands

Received 13 November, 2006

Revised 1 April, 2007

Accepted 4 April, 2007

Correspondence to Dr Luis M. Ruilope, Hypertension Unit, Hospital 12 de Octubre, Avenue Córdoba, s/n 28041, Madrid, Spain Tel: +34 91 3908198; fax: +34 91 3908035; e-mail: ruilope@ad-hocbox.com

© 2007 Lippincott Williams & Wilkins, Inc.