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

Diabetes Care. 2006 Jun;29(6):1220-6. doi: 10.2337/dc05-2465.

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.

Research design and 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atorvastatin
  • Blood Pressure
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood*
  • Coronary Disease / blood*
  • Coronary Disease / complications
  • Coronary Disease / drug therapy
  • Coronary Disease / physiopathology
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Angiopathies / blood*
  • Diabetic Angiopathies / drug therapy
  • Diabetic Angiopathies / physiopathology
  • Dose-Response Relationship, Drug
  • Female
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Pyrroles / therapeutic use*
  • Triglycerides / blood

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Triglycerides
  • Atorvastatin