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(Circulation. 2004;110:1557-1563.)
© 2004 American Heart Association, Inc.

Coronary Heart Disease

Effect of Pravastatin on Cardiovascular Events in People With Chronic Kidney Disease

Marcello Tonelli, MD, SM; Chris Isles, MD; Gary C. Curhan, MD, ScD; Andrew Tonkin, MD; Marc A. Pfeffer, MD, PhD; James Shepherd, MD; Frank M. Sacks, MD; Curt Furberg, MD; Stuart M. Cobbe, MD; John Simes, MD, MSc; Timothy Craven, MSPH; Malcolm West

From the Divisions of Nephrology and Critical Care Medicine, University of Alberta, and the Institute of Health Economics, Edmonton, Alberta, Canada (M.T.); Department of Medicine, Dumfries and Galloway Royal Infirmary, Dumfries, Scotland, UK (C.I.); Departments of Epidemiology (G.C.C.) and Nutrition (F.M.S.), Harvard School of Public Health, Boston, Mass; Channing Laboratory (G.C.C., F.M.S.) and Cardiovascular Division (M.A.P.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia (A.T.); University of Glasgow, Glasgow, Scotland, UK (J. Shepherd); Wake Forest University School of Medicine, Winston-Salem, NC (C.F., T.C.); University of Sydney, Sydney, Australia (J. Simes); and Department of Medicine, University of Queensland, Brisbane, Australia (M.W.).

Correspondence to Dr Marcello Tonelli, Division of Nephrology, University of Alberta, 7-129 Clinical Science Building, 8440 112 St, Edmonton, Alberta T6G 2G3, Canada. E-mail mtonelli{at}ualberta.ca

Received February 13, 2004; revision received May 17, 2004; accepted May 21, 2004.

Background— Limited data describe the cardiovascular benefit of HMG-CoA reductase inhibitors (statins) in people with moderate chronic kidney disease (CKD). The objective of this analysis was to determine whether pravastatin reduced the incidence of cardiovascular events in people with or at high risk for coronary disease and with concomitant moderate CKD.

Methods and Results— We analyzed data from the Pravastatin Pooling Project (PPP), a subject-level database combining results from 3 randomized trials of pravastatin (40 mg daily) versus placebo. Of 19 700 subjects, 4491 (22.8%) had moderate CKD, defined by an estimated glomerular filtration rate of 30 to 59.99 mL/min per 1.73 m² body surface area. The primary outcome was time to myocardial infarction, coronary death, or percutaneous/surgical coronary revascularization. Moderate CKD was independently associated with an increased risk of the primary outcome (adjusted HR 1.26, 95% CI 1.07 to 1.49) compared with those with normal renal function. Among the 4491 subjects with moderate CKD, pravastatin significantly reduced the incidence of the primary outcome (HR 0.77, 95% CI 0.68 to 0.86), similar to the effect of pravastatin on the primary outcome in subjects with normal kidney function (HR 0.78, 95% CI 0.65 to 0.94). Pravastatin also appeared to reduce the total mortality rate in those with moderate CKD (adjusted HR 0.86, 95% CI 0.74 to 1.00, P=0.045).

Conclusions— Pravastatin reduces cardiovascular event rates in people with or at risk for coronary disease and concomitant moderate CKD, many of whom have serum creatinine levels within the normal range. Given the high risk associated with CKD, the absolute benefit that resulted from use of pravastatin was greater than in those with normal renal function.

Key Words: kidney failure • statins • pravastatin • trials

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