title: 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.
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.
  
  
  CONCLUSIONS
  Intensive management of dyslipidemia in older patients with stable coronary heart disease may have beneficial effects on renal function and SUA.
authors.affiliation: Cardiology Division, UCSF School of Medicine, 5th Floor, 2823 Fresno Street, Fresno, CA, 93703, USA. pdeedwania@fresno.ucsf.edu.
authors.forename: Prakash C
authors.initials: PC
authors.lastname: Deedwania
authors.affiliation: Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Stone
authors.affiliation: Pfizer, New York, NY, USA.
authors.forename: Rana S
authors.initials: RS
authors.lastname: Fayyad
authors.affiliation: Pfizer, New York, NY, USA.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Laskey
authors.affiliation: Relypsa, Redwood City, CA, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wilson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000069059:Atorvastatin / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000188:drug therapy; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000188:drug therapy*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D008297:Male; D017035:Pravastatin / Q000627:therapeutic use; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology; D014527:Uric Acid / Q000097:blood*
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014527:Uric Acid; D000069059:Atorvastatin; D017035:Pravastatin