title: Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the Treating to New Targets (TNT) study.
abstract: OBJECTIVE
  The Treating to New Targets study showed that intensive lipid-lowering therapy with atorvastatin 80 mg/day provides significant clinical benefit beyond that afforded by atorvastatin 10 mg/day in patients with stable coronary heart disease (CHD). The objective of our study was to investigate whether similar benefits of high-dose intensive atorvastatin therapy can be achieved in patients with CHD and diabetes.
  
  
  METHODS
  A total of 1,501 patients with diabetes and CHD, with LDL cholesterol levels of <130 mg/dl, were randomized to double-blind therapy with either atorvastatin 10 (n = 753) or 80 (n = 748) mg/day. Patients were followed for a median of 4.9 years. The primary end point was the time to first major cardiovascular event, defined as death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke.
  
  
  RESULTS
  End-of-treatment mean LDL cholesterol levels were 98.6 mg/dl with atorvastatin 10 mg and 77.0 mg/dl with atorvastatin 80 mg. A primary event occurred in 135 patients (17.9%) receiving atorvastatin 10 mg, compared with 103 patients (13.8%) receiving atorvastatin 80 mg (hazard ratio 0.75 [95% CI 0.58-0.97], P = 0.026). Significant differences between the groups in favor of atorvastatin 80 mg were also observed for time to cerebrovascular event (0.69 [0.48-0.98], P = 0.037) and any cardiovascular event (0.85 [0.73-1.00], P = 0.044). There were no significant differences between the treatment groups in the rates of treatment-related adverse events and persistent elevations in liver enzymes.
  
  
  CONCLUSIONS
  Among patients with clinically evident CHD and diabetes, intensive therapy with atorvastatin 80 mg significantly reduced the rate of major cardiovascular events by 25% compared with atorvastatin 10 mg.
authors.affiliation: Department of Vascular Biochemistry, Royal Infirmary, Glasgow G4 OSF, U.K. jshepherd@gri-biochem.org.uk
authors.forename: James
authors.initials: J
authors.lastname: Shepherd
authors.forename: Philip
authors.initials: P
authors.lastname: Barter
authors.forename: Rafael
authors.initials: R
authors.lastname: Carmena
authors.forename: Prakash
authors.initials: P
authors.lastname: Deedwania
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Fruchart
authors.forename: Steven
authors.initials: S
authors.lastname: Haffner
authors.forename: Judith
authors.initials: J
authors.lastname: Hsia
authors.forename: Andrei
authors.initials: A
authors.lastname: Breazna
authors.forename: John
authors.initials: J
authors.lastname: LaRosa
authors.forename: Scott
authors.initials: S
authors.lastname: Grundy
authors.forename: David
authors.initials: D
authors.lastname: Waters
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D001794:Blood Pressure; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003327:Coronary Disease / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D014280:Triglycerides; D000069059:Atorvastatin