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Randomized Controlled Trial
. 2015 Dec;32(12):1055-65.
doi: 10.1007/s40266-015-0328-z.

Improvement in Renal Function and Reduction in Serum Uric Acid with Intensive Statin Therapy in Older Patients: A Post Hoc Analysis of the SAGE Trial

Prakash C Deedwania  1 , Peter H Stone  2 , Rana S Fayyad  3 , Rachel E Laskey  3 , Daniel J Wilson  4
Affiliations
Randomized Controlled Trial

Improvement in Renal Function and Reduction in Serum Uric Acid with Intensive Statin Therapy in Older Patients: A Post Hoc Analysis of the SAGE Trial

Prakash C Deedwania et al. Drugs Aging. 2015 Dec.

Abstract

Background: Improvement in renal function and decreases in serum uric acid (SUA) have been reported following prolonged high-intensity statin (HMG-CoA reductase inhibitor) therapy. This post hoc analysis of the SAGE trial examined the effect of intensive versus less intensive statin therapy on renal function, safety, and laboratory parameters, including SUA, in elderly coronary artery disease (CAD) patients (65-85 years) with or without chronic kidney disease (CKD).

Methods: Patients were randomized to atorvastatin 80 mg/day or pravastatin 40 mg/day and treated for 12 months. Patients were stratified using Modification of Diet in Renal Disease (MDRD) estimated glomerular filtration rates (eGFRs) in CKD (eGFR <60 mL/min/1.73 m(2)) and non-CKD populations.

Results: Of the 893 patients randomized, 858 had complete renal data and 418 of 858 (49%) had CKD (99% Stage 3). Over 12 months, eGFR increased with atorvastatin and remained stable with pravastatin (+2.38 vs. +0.18 mL/min/1.73 m(2), respectively; p < 0.0001). MDRD eGFR improved significantly in both CKD treatment arms; however, the increased eGFR in patients without CKD was significantly greater with atorvastatin (+2.08 mL/min/1.73 m(2)) than with pravastatin (-1.04 mL/min/1.73 m(2)). Modest reductions in SUA were observed in both treatment arms, but a greater fall occurred with atorvastatin than with pravastatin (-0.52 vs. -0.09 mg/dL, p < 0.0001). Change in SUA correlated negatively with changes in eGFR and positively with changes in low-density lipoprotein cholesterol. Reports of myalgia were rare (3.6% CKD; 5.7% non-CKD), and there were no episodes of rhabdomyolysis. Elevated serum alanine and aspartate transaminase to >3 times the upper limit of normal occurred in 4.4% of atorvastatin- and 0.2% of pravastatin-treated patients.

Conclusion: Intensive management of dyslipidemia in older patients with stable coronary heart disease may have beneficial effects on renal function and SUA.

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Figures

Fig. 1
Fig. 1
Patient enrollment in the SAGE trial and inclusion in the renal analysis cohort. *Includes two patients with cardiac events. CKD chronic kidney disease, eGFR estimated glomerular filtration rate
Fig. 2
Fig. 2
Changes in estimated glomerular filtration rate (eGFR) from baseline (least square mean ± standard error) following 12 months’ treatment with atorvastatin 80 mg/day or pravastatin 40 mg/day in all patients in the SAGE renal cohort and according to chronic kidney disease status. LDL-C low-density lipoprotein cholesterol
Fig. 3
Fig. 3
Changes in estimated glomerular filtration rate (eGFR) from baseline (least square mean ± standard error) following 12 months’ treatment with atorvastatin 80 mg/day or pravastatin 40 mg/day, grouped by quartile ranges of changes in low-density lipoprotein cholesterol from baseline. CKD chronic kidney disease, eGFR estimated glomerular filtration rate
See this image and copyright information in PMC

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