Treatment with atorvastatin to the National Cholesterol Educational Program goal versus 'usual' care in secondary coronary heart disease prevention. The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study

Curr Med Res Opin. 2002;18(4):220-8. doi: 10.1185/030079902125000787.


Background: Atorvastatin is very effective in reducing plasma low-density lipoprotein cholesterol (LDL-C) levels. However, there is no long-term survival study that evaluated this statin.

Patients-methods: To assess the effect of atorvastatin on morbidity and mortality (total and coronary) of patients with established coronary heart disease (CHD), 1600 consecutive patients were randomised either to atorvastatin or to 'usual' medical care. The dose of atorvastatin was titrated from 10 to 80 mg/day, in order to reach the National Cholesterol Education Program (NCEP) goal of LDL-C <100 mg/dl (2.6 mmol/l). All patients were followed up for a mean period of 3 years.

Main outcome measures: Primary endpoints of the study were defined as death, non-fatal myocardial infarction, unstable angina, congestive heart failure, revascularisation (coronary morbidity) and stroke. Secondary endpoints were the safety and efficacy of the hypolipidaemic drugs as well as the cost-effectiveness of atorvastatin.

Results: The mean dosage of atorvastatin was 24 mg/day. This statin reduced total chlesterol by 36%, LDL-C by 46%, triglycerides by 31%, and non-high-density lipoprotein cholesterol (non-HDL-C) by 44%, while it increased HDL-C by 7%; all these changes were significant. The NCEP LDL-C and non-HDL-C treatment goals were reached by 95% (n = 759) and 97% (n = 776), respectively, of patients on atorvastatin. Only 14% of the 'usual' care patients received any hypolipidaemic drugs throughout the study and 3% of them reached the NCEP LDL-C treatment goal. The cost per quaility-adjusted life-year gained with atorvastatin was estimated at $US 8350. During this study 196 (24.5%) CHD patients on 'usual' care had a CHD recurrent event or died vs. 96 (12%) CHD patients on atorvastatin; risk ratio (RR) 0.49, confidence interval (CI) 0.27-0.73, p < 0.0001. In detail, atorvastatin reduced, in comparison to 'usual' care, total mortality (RR 0.57, CI 0.39-0.78, p = 0.0021), coronary mortality (RR 0.53, CI 0.29-0.74, p = 0.0017), coronary morbidity (RR 0.46, CI 0.25-0.71, p < 0.0001), and stroke (RR 0.53, CI 0.30-0.82, p = 0.034). All subgroups of patients (women, those with diabetes mellitus, arterial hypertension, age 60 to 75 years, congestive heart failure, recent unstable angina or prior revascularisation) benefited from treatment with atorvastatin. Withdrawal of patients because of side-effects from the atorvastatin group was low (0.75%) and similar to that of the 'usual' care group (0.4%).

Conclusions: Long-term treatment of CHD patients with atorvastatin to achieve NCEP lipid targets significantly reduces total and coronary mortality, coronary morbidity and stroke, in comparison to patients receiving 'usual' medical care. Treatment with atorvastatin is well tolerated and cost-effective.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Anticholesteremic Agents / therapeutic use*
  • Atorvastatin
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Cholesterol, VLDL / blood
  • Coronary Disease / blood
  • Coronary Disease / prevention & control*
  • Cost-Benefit Analysis
  • Female
  • Greece
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • National Health Programs
  • Prospective Studies
  • Pyrroles / therapeutic use*
  • Treatment Outcome
  • Triglycerides / blood


  • Anticholesteremic Agents
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Cholesterol, VLDL
  • Heptanoic Acids
  • Pyrroles
  • Triglycerides
  • Atorvastatin