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Received July 27, 2005
Accepted on September 1, 2005

CLINICAL SCIENCE: Chronic Kidney Disease

Effect of Pravastatin in People with Diabetes and Chronic Kidney Disease

Marcello Tonelli ^*1, Anthony Keech , Jim Shepherd ^||, Frank Sacks ^¶, Andrew Tonkin ^#, Chris Packard ^*, Marc Pfeffer , John Simes , Chris Isles , Curt Furberg , Malcolm West ^||, Tim Craven , and Gary Curhan; ^¶¶##

Divisions of *Nephrology and Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada; Institute of Health Economics, Edmonton, Alberta, Canada; NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia; ||University of Glasgow, Glasgow, Scotland, United Kingdom; Departments of ¶Nutrition and ¶¶Epidemiology, Harvard School of Public Health, Boston, Massachusetts; #Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; *Department of Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow, Scotland, United Kingdom; Cardiovascular Division and ##Renal Division and Channing Laboratory, Brigham and Women’s Hospital, Boston, Massachusetts; Department of Medicine, Dumfries and Galloway Royal Infirmary, Dumfries, Scotland, United Kingdom; and Wake Forest University School of Medicine, Winston-Salem, North Carolina; ||||Department of Medicine, University of Queensland, Brisbane, Australia

¹ To whom correspondence should be addressed. E-mail: mtonelli{at}ualberta.ca.

	Abstract

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.

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