Statins for Renal Patients: A Fiddler on the Roof?
Table 1
Overview of major statin studies.
Study
Patient population
Followup
Treatment
Outcome
Results
Overview of renal outcomes
GREACE
Post hoc subgroup analysis
1,600 patients with dyslipidemia and CAD
3 years
Atorvastatin 10–80 mg/day or usual medical care
Rate of kidney function decline
CrCl had a 12% increase in atorvastatin group () CrCl had a 5.2% decrease in patients not treated with statins () CrCl had a 4.9% increase in the usual care group on various statins
ALLIANCE
Post hoc subgroup analysis
2,442 patients with dyslipidemia
4 years
Atorvastatin 10–80 mg/day or usual medical care
Rate of kidney function decline
CrCl did not change in the atorvastatin group versus baseline CrCl declined by 4.4% in the usual care group ( versus baseline)
CARE
Post hoc subgroup analysis
3,384 individuals of whom 690 (20.4%) had GFR < 60 mL/min per 1.73 m2
4 years
Pravastatin 40 mg/day versus placebo
Change in GFR
The decline in the pravastatin group versus placebo was nonsignificant In patients with GFR < 40 mL/min per 1.73 m2, the rate of change in the pravastatin versus placebo group was 2.5 mL/min per 1.73 m2/year slower (95% CI: 1.4–3.6; )
SHARP
Randomized double blind, multicenter trial
9,270 participants, including 3000 receiving hemodialysis
4.9 years
Ezetimibe 10 mg/day + simvastatin 20 mg/day versus placebo versus simvastatin 20 mg/day
ESRD, major atherosclerotic events
17% reduction in major atherosclerotic events No difference of progression to ESRD
PLANET I
Randomized double blind, multicenter trial
325 patients with diabetes who had proteinuria and hypercholesterolemia
1 year
Rosuvastatin 10 mg/day or rosuvastatin 40 mg/day versus atorvastatin 80 mg/day
Change in urinary protein excretion (urinary protein/ creatinine ratio)
Atorvastatin significantly reduced proteinuria by about 15% rosuvastatin had no significant effect on proteinuria Patients on atorvastatin lost 1 to 2 mL/min per 1.73 m2, those on rosuvastatin 10 mg/day lost 4 mL/min per 1.73 m2, and those on rosuvastatin 40 mg/day lost 8 mL/min per 1.73 m2 over 52 weeks
PLANET II
Randomized double-blind, multicenter trial
220 patients without diabetes who had proteinuria and hypercholesterolemia
1 year
Rosuvastatin 10 mg/day or rosuvastatin 40 mg/day versus atorvastatin 80 mg/day
Change in urinary protein excretion (urinary protein/ creatinine ratio)
Atorvastatin reduced proteinuria by 23.8% () Significant decline in GFR with rosuvastatin No significant difference in the amount of lipid lowering was reported among the treatment groups
27 studies (21 with data for GFR), 39,704 participants
Different statins
Change in GFR
Statins slowed the loss of GFR by a mean of 1.22 mL/min/year; 95% CI: 0.44–2.00 In studies of CVD, patients were slower than controls (0.93 mL/min/year, 95% CI: 0.10–1.76), with statistical significance
Statins reduced albuminuria and proteinuria in 13 studies The reduction of excretion was greater among studies with greater baseline albuminuria or proteinuria
Overview of cardiovascular outcomes in patients with kidney disease
Pravastatin Pooling Project (WOSCOPS, CARE and LIPID)
Randomized double-blind, multicenter trial
4,491 patients with or without CAD and with moderate CKD (GFR, 30–60 mL/min/1.73 m2)
Pravastatin 40 mg/day versus placebo
Time to MI, coronary death, or PCR
Significant reduction in primary outcome in statin-treated patients, with moderate CKD (HR: 0.77, 95% CI: 0.68–0.86); reduction in total mortality in treated patients
4D Study
Randomized double blind, multicenter trial
1,255 hemodialysis patients, with type 2 diabetes
4 years
Atorvastatin 20 mg/day versus placebo
Composite of cardiac death, nonfatal MI, and stroke
No significant difference in primary endpoint with statin treatment, but increased risk for fatal stroke ()
AURORA
Randomized double blind, multicenter trial
2,776 patients receiving long-term hemodialysis
3.2 years
Rosuvastatin 10 mg/day versus placebo
Composite of cardiac death, nonfatal MI, and stroke
Rosuvastatin lowered the LDL level () but had no significant effect on primary endpoint
GREACE: Greek Atorvastatin and Coronary Heart Disease Evaluation; ALLIANCE: Aggressive Lipid-Lowering Initiation Abates New Cardiac Events; CARE: Cholesterol And Recurrent Events; SHARP: Study of Heart and Renal Protection; PLANET: Prospective Evaluation of Proteinuria and Renal Function in Diabetic Patients; WOSCOPS: West of Scotland Coronary Prevention Study; LIPID: Long-Term Intervention with Pravastatin in Ischaemic Disease; 4D Study: Die Deutsche Diabetes Dialyse Studie; AURORA: A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis; CAD: coronary artery disease; CrCl: creatinine clearance; GFR: glomerular filtration rate; ESRD: end-stage renal disease; CVD: cardiovascular disease; CKD: chronic kidney disease; PCR: percutaneous coronary revascularization.