Effect of pravastatin in people with diabetes and chronic kidney disease.
Although diabetes is a major cause of chronic kidney disease (CKD), limited data describe the cardiovascular benefit of hydroxymethyl glutaryl CoA reductase inhibitors (statins) in people with both of these conditions. This study sought to determine whether pravastatin reduced the incidence of first or recurrent cardiovascular events in people with non-dialysis-dependent CKD and concomitant diabetes, using data from three randomized trials of pravastatin 40 mg daily versus placebo. CKD was defined by estimated GFR <60 or 60 to 89.9 ml/min per 1.73 m2 with proteinuria. Of 19,737 patients, 4099 (20.8%) had CKD but not diabetes at baseline, 873 (4.4%) had diabetes but not CKD, and 571 (2.9%) had both conditions. The primary composite outcome was time to myocardial infarction, coronary death, or percutaneous/surgical coronary revascularization. Median follow-up was 64 mo. After adjustment for trial and random treatment assignment, the incidence of the primary outcome was lowest in individuals with neither CKD nor diabetes (15.2%), intermediate in individuals with only CKD (18.6%) or only diabetes (21.3%), and highest in individuals with both characteristics (27.0%). Pravastatin reduced the relative likelihood of the primary outcome to a similar extent in subgroups defined by the presence or absence of CKD and diabetes. For example, pravastatin was associated with a significant reduction in the relative risk of the primary outcome by 25% in patients with CKD and concomitant diabetes and by 24% in individuals with neither characteristic. However, the absolute reduction in the risk of the primary outcome as a result of pravastatin use was highest in patients with both CKD and diabetes (6.4%) and lowest in individuals with neither characteristic (3.5%). In conclusion, stage 2 or early stage 3 CKD and diabetes both are associated with higher cardiovascular risk, and pravastatin reduces cardiovascular event rates in people with neither, one, or both characteristics. Given the high absolute benefit of pravastatin in patient with diabetes and stage 2 or early stage 3 CKD, this population in particular should be targeted for widespread use of statins. Additional studies are needed to determine whether these benefits apply to patients with more severe CKD, and recruitment to such studies should be given high priority.
Tonelli
Marcello
M
Division of Nephrology, University of Alberta, Edmonton, Alberta, Canada. mtonelli@ualberta.ca
Keech
Anthony
A
Shepherd
Jim
J
Sacks
Frank
F
Tonkin
Andrew
A
Packard
Chris
C
Pfeffer
Marc
M
Simes
John
J
Isles
Chris
C
Furberg
Curt
C
West
Malcolm
M
Craven
Tim
T
Curhan
Gary
G
D000328:Adult; D017677:Age Distribution; D000368:Aged; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000453:epidemiology* / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use*; D015995:Prevalence; D011336:Probability; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy; D018570:Risk Assessment; D017678:Sex Distribution; D016896:Treatment Outcome
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin