Pravastatin for secondary prevention of cardiovascular events in persons with mild chronic renal insufficiency.
BACKGROUND
Cardiovascular disease is a common cause of morbidity and death in persons with renal insufficiency. Although 3-hydroxy-3methylglutaryl coenzyme A reductase inhibitors (statins) are effective for secondary prevention of cardiovascular events in the general population, they have not been specifically studied in chronic renal insufficiency.


OBJECTIVE
To determine whether pravastatin is effective and safe for secondary prevention of cardiovascular events in persons with chronic renal insufficiency.


METHODS
Post hoc subgroup analysis of a randomized, double-blind, placebo-controlled trial.


METHODS
The Cholesterol and Recurrent Events (CARE) study, a randomized trial of pravastatin versus placebo in 4159 participants with previous myocardial infarction and total plasma cholesterol levels less than 6.21 mmol/L (<240 mg/dL).


METHODS
1711 participants with chronic renal insufficiency defined by creatinine clearance less than or equal to 75 mL/min, using the Cockcroft-Gault equation.


METHODS
The primary outcome was death from coronary disease or symptomatic nonfatal myocardial infarction.


RESULTS
After a median follow-up of 58.9 months, the incidence of the primary end point was lower in participants receiving pravastatin than in those receiving placebo (adjusted hazard ratio, 0.72 [95% CI, 0.55 to 0.95]; P = 0.02). Pravastatin was associated with lower adjusted hazard ratios for major coronary events (0.72 [CI, 0.59 to 0.88]; P = 0.001) and coronary revascularization (0.65 [CI, 0.50 to 0.83]; P = 0.001), but not total mortality (0.81 [CI, 0.61 to 1.08]; P = 0.14) or stroke (0.62 [CI, 0.39 to 1.00]; P = 0.051). Tests for interaction suggested that the observed benefit was independent of the presence and severity of renal insufficiency. Incidence of side effects was similar in persons receiving pravastatin and those receiving placebo.


CONCLUSIONS
These data suggest that pravastatin is effective and appears safe for secondary prevention of cardiovascular events in persons with mild chronic renal insufficiency. Since statins may be underused in this setting, physicians should consider prescribing them for patients with chronic renal insufficiency and known coronary disease.
Tonelli
Marcello
M
Division of Nephrology and Immunology, University of Alberta, Clinical Sciences Building, Suite 11-108C, 8440 112 Street, Edmonton, Alberta T6B 2B7, Canada.
Moyé
Lemuel
L
Sacks
Frank M
FM
Kiberd
Bryce
B
Curhan
Gary
G
D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control*; D003404:Creatinine / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000652:urine; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D017035:Pravastatin / Q000009:adverse effects / Q000627:therapeutic use*; D020521:Stroke / Q000517:prevention & control
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D003404:Creatinine; D017035:Pravastatin