Intensive lipid lowering with atorvastatin in patients with coronary artery disease, diabetes, and chronic kidney disease.
OBJECTIVE
To investigate the effect of intensive lipid lowering with high-dose atorvastatin on the incidence of major cardiovascular events compared with low-dose atorvastatin in patients with coronary artery disease and type 2 diabetes, with and without chronic kidney disease (CKD).


METHODS
Following 8 weeks' open-label therapy with atorvastatin (10 mg/d), 10,001 patients with coronary artery disease were randomized to receive double-blind therapy with either 80 mg/d or 10 mg/d of atorvastatin between July 1, 1998, and December 31, 1999. Of 1501 patients with diabetes, renal data were available for 1431. Patients with CKD were defined as having a baseline estimated glomerular filtration rate (eGFR) below 60 mL/min per 1.73 m2, using the Modification of Diet in Renal Disease equation.


RESULTS
After a median follow-up of 4.8 years, 95 (17.4%) of 546 patients with diabetes and CKD experienced a major cardiovascular event vs 119 (13.4%) of 885 patients with diabetes and normal eGFRs (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.00-1.72; P<.05). Compared with 10 mg of atorvastatin, 80 mg of atorvastatin reduced the relative risk of major cardiovascular events by 35% in patients with diabetes and CKD (20.9% [57/273] vs 13.9% [38/273]; HR, 0.65; 95% CI, 0.43-0.98; P=.04) and by 10% in patients with diabetes and normal eGFR (14.1% [62/441] vs 12.8% [57/444]; HR, 0.90; 95% CI, 0.63-1.29; P=.56). The absolute risk reduction in patients with diabetes and CKD was substantial, yielding a number needed to treat of 14 to prevent 1 major cardiovascular event over 4.8 years. Both treatments were well tolerated.


CONCLUSIONS
Patients with diabetes, stable coronary artery disease, and mild to moderate CKD experience marked reduction in cardiovascular events with intensive lipid lowering, in contrast to previous observations in patients with diabetes and end-stage renal disease.


BACKGROUND
clinicaltrials.gov identifier: NCT00327691.
Shepherd
James
J
University of Glasgow, United Kingdom. jshepherd@gri-biochem.org.uk
Kastelein
John P
JP
Bittner
Vera A
VA
Carmena
Rafael
R
Deedwania
Prakash C
PC
Breazna
Andrei
A
Dobson
Stephen
S
Wilson
Daniel J
DJ
Zuckerman
Andrea L
AL
Wenger
Nannette K
NK
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D000069059:Atorvastatin; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control*; D003327:Coronary Disease / Q000150:complications* / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000008:administration & dosage*; D012306:Risk; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D008055:Lipids; D011758:Pyrroles; D000069059:Atorvastatin