Intensive lipid lowering with atorvastatin in patients with coronary heart disease and chronic kidney disease: the TNT (Treating to New Targets) study.
OBJECTIVE
This subanalysis of the TNT (Treating to New Targets) study investigates the effects of intensive lipid lowering with atorvastatin in patients with coronary heart disease (CHD) with and without pre-existing chronic kidney disease (CKD).


BACKGROUND
Cardiovascular disease is a major cause of morbidity and mortality in patients with CKD.


METHODS
A total of 10,001 patients with CHD were randomized to double-blind therapy with atorvastatin 80 mg/day or 10 mg/day. Patients with CKD were identified at baseline on the basis of an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) using the Modification of Diet in Renal Disease equation. The primary efficacy outcome was time to first major cardiovascular event.


RESULTS
Of 9,656 patients with complete renal data, 3,107 had CKD at baseline and demonstrated greater cardiovascular comorbidity than those with normal eGFR (n = 6,549). After a median follow-up of 5.0 years, 351 patients with CKD (11.3%) experienced a major cardiovascular event, compared with 561 patients with normal eGFR (8.6%) (hazard ratio [HR] = 1.35; 95% confidence interval [CI] 1.18 to 1.54; p < 0.0001). Compared with atorvastatin 10 mg, atorvastatin 80 mg reduced the relative risk of major cardiovascular events by 32% in patients with CKD (HR = 0.68; 95% CI 0.55 to 0.84; p = 0.0003) and 15% in patients with normal eGFR (HR = 0.85; 95% CI 0.72 to 1.00; p = 0.049). Both doses of atorvastatin were well tolerated in patients with CKD.


CONCLUSIONS
Aggressive lipid lowering with atorvastatin 80 mg was both safe and effective in reducing the excess of cardiovascular events in a high-risk population with CKD and CHD.
Shepherd
James
J
University of Glasgow, Glasgow, United Kingdom. jshepherd@gri-biochem.org.uk
Kastelein
John J P
JJ
Bittner
Vera
V
Deedwania
Prakash
P
Breazna
Andrei
A
Dobson
Stephen
S
Wilson
Daniel J
DJ
Zuckerman
Andrea
A
Wenger
Nanette K
NK
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000503:physiopathology; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D012306:Risk; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011758:Pyrroles; D014280:Triglycerides; D000069059:Atorvastatin