Effect of pravastatin on cardiovascular events in people with chronic kidney disease.
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.


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.
Tonelli
Marcello
M
Division of Nephrology, University of Alberta, 7-129 Clinical Science Building, 8440 112 St, Edmonton, Alberta T6G 2G3, Canada. mtonelli@ualberta.ca
Isles
Chris
C
Curhan
Gary C
GC
Tonkin
Andrew
A
Pfeffer
Marc A
MA
Shepherd
James
J
Sacks
Frank M
FM
Furberg
Curt
C
Cobbe
Stuart M
SM
Simes
John
J
Craven
Timothy
T
West
Malcolm
M
D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000706:statistics & numerical data; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D002908:Chronic Disease; D015897:Comorbidity; D003327:Coronary Disease / Q000150:complications; D003404:Creatinine / Q000097:blood; D016208:Databases, Factual; D004311:Double-Blind Method; D004341:Drug Evaluation; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D007674:Kidney Diseases / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D009204:Myocardial Revascularization / Q000706:statistics & numerical data; D017035:Pravastatin / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012306:Risk
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D003404:Creatinine; D017035:Pravastatin