International Journal of Nephrology / 2012 / Article / Tab 1

Review Article

Statins for Renal Patients: A Fiddler on the Roof?

Table 1

Overview of major statin studies.

StudyPatient populationFollowupTreatment OutcomeResults

Overview of renal outcomes

GREACEPost hoc subgroup analysis1,600 patients with dyslipidemia and CAD3 yearsAtorvastatin 10–80 mg/day or usual medical careRate of kidney function declineCrCl 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

ALLIANCEPost hoc subgroup analysis2,442 patients with dyslipidemia4 yearsAtorvastatin 10–80 mg/day or usual medical careRate of kidney function declineCrCl did not change in the atorvastatin group versus baseline
CrCl declined by 4.4% in the usual care group ( versus baseline)

CAREPost hoc subgroup analysis3,384 individuals of whom 690 (20.4%) had GFR < 60 mL/min per 1.73 m24 yearsPravastatin 40 mg/day versus placeboChange in GFRThe 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; )

SHARPRandomized double blind, multicenter trial9,270 participants, including 3000 receiving hemodialysis4.9 yearsEzetimibe 10 mg/day + simvastatin 20 mg/day versus placebo versus simvastatin 20 mg/dayESRD, major atherosclerotic events17% reduction in major atherosclerotic events
No difference of progression to ESRD

PLANET IRandomized double blind, multicenter trial325 patients with diabetes who had proteinuria and hypercholesterolemia1 yearRosuvastatin 10 mg/day or rosuvastatin 40 mg/day versus atorvastatin 80 mg/dayChange 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 IIRandomized double-blind, multicenter trial220 patients without diabetes who had proteinuria and hypercholesterolemia1 yearRosuvastatin 10 mg/day or rosuvastatin 40 mg/day versus atorvastatin 80 mg/dayChange 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

Strippoli et al.
[23]
Meta-analysis11 studies, 548 patientsDifferent statinsChange in GFRStatins did not improve GFR

Sandhu et al.
[21]
Metaanalysis27 studies (21 with data for GFR), 39,704 participantsDifferent statinsChange in GFRStatins 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

Douglas et al.
[22]
Metaanalysis15 studies, 1,384 patientsDifferent statinsChange in urinary protein excretionStatins 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 trial4,491 patients with or without CAD and with moderate CKD (GFR, 30–60 mL/min/1.73 m2)Pravastatin 40 mg/day versus placeboTime to MI, coronary death, or PCRSignificant 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 StudyRandomized double blind, multicenter trial1,255 hemodialysis patients, with type 2 diabetes4 yearsAtorvastatin 20 mg/day versus placeboComposite of cardiac death, nonfatal MI, and strokeNo significant difference in primary endpoint with statin treatment, but increased risk for fatal stroke ( )

AURORARandomized double blind, multicenter trial2,776 patients receiving long-term hemodialysis3.2 yearsRosuvastatin 10 mg/day versus placeboComposite of cardiac death, nonfatal MI, and strokeRosuvastatin 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.

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