ASPEN study

• cardiovascular disease (CVD) risk is increased in type 2 diabetes
  • purpose of this study was to assess the effect of 10 mg of atorvastatin versus placebo on CVD prevention in subjects with type 2 diabetes and LDL cholesterol levels below contemporary guideline targets
• study design
  • subjects were randomly assigned to receive 10 mg of atorvastatin or placebo in a 4-year, double-blind, parallel-group study
  • composite primary end point comprised cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, recanalization, coronary artery bypass surgery, resuscitated cardiac arrest, and worsening or unstable angina requiring hospitalization
  • male and female subjects, aged 40–75 years, were eligible for inclusion if they had type 2 diabetes by the World Health Organization definition >= 3 years before screening. LDL cholesterol criteria were:
    • 1) LDL cholesterol <= 140 mg/dl (3.6 mmol/l) if subjects had documented myocardial infarction or an interventional procedure >3 months before screening or
    • 2) LDL cholesterol <= 160 mg/dl (4.1 mmol/l) if not. Triglyceride levels were required to be<= 600 mg/dl (6.8 mmol/l) at all visits
• study results
  • 2,410 subjects with type 2 diabetes were randomized. Mean LDL cholesterol reduction in the atorvastatin group over 4 years was 29% versus placebo (P < 0.0001)
  • when compared atorvastatin versus placebo, composite primary end point rates were 13.7 and 15.0%, respectively (hazard ratio 0.90 [95% CI 0.73-1.12])
  • in the subset of 1,905 subjects without prior myocardial infarction or interventional procedure
    • 10.4% of atorvastatin- and 10.8% of placebo-treated subjects experienced a primary end point (0.97 [0.74-1.28])
    • in the 505 subjects with prior myocardial infarction or interventional procedure, 26.2% of atorvastatin- and 30.8% of placebo-treated subjects experienced a primary end point (0.82 [0.59-1.15])
    • relative risk reductions in fatal and nonfatal myocardial infarction were 27% overall (P = 0.10) and 19% (P = 0.41) and 36% (P = 0.11) for subjects without and with prior myocardial infarction or interventional procedure, respectively
• conclusions
  • composite end point reductions were not statistically significant
  • authors suggest that the result may relate to the overall study design, the types of subjects recruited, the nature of the primary end point, and the protocol changes required because of changing treatment guidelines
    • the study authors suggest, for the aforementioned reasons, the results of the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN) did not confirm the benefit of therapy but do not detract from the imperative that the majority of diabetic patients are at risk of coronary heart disease and deserve LDL cholesterol lowering to the currently recommended targets

Reference:

1. Knopp RH et al. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in non-insulin-dependent diabetes mellitus (ASPEN).Diabetes Care. 2006 Jul;29(7):1478-85.