Atorvastatin fails to demonstrate significant benefit in treatment of CV disease in patients with diabetes

Atorvastatin showed no statistically significant difference in the reduction of a composite cardiovascular disease (CVD) end point in type 2 diabetes patients, according to a randomized, double-blind, parallel-group study.

The 4-year results of the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN) were published in Diabetes Care.

A total of 2,410 subjects with type 2 diabetes and LDL cholesterol levels below contemporary guideline targets were randomized to atorvastatin 10 mg (n=1,211) or placebo (n=1,199).

Atorvastatin and placebo resulted in composite primary end point rates of 13.7% and 15.0%, respectively (HR=0.90; 95% CI, 0.73–1.12; P=.34). The atorvastatin group demonstrated a mean LDL cholesterol reduction of 29% versus placebo (P<.0001).

In a 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 (HR=0.97; 95% CI, 0.74–1.28).

Among the remaining 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 (HR=0.82; 95% CI, 0.59–1.15).

Relative risk reductions in fatal and nonfatal myocardial infarction were 27% (P=.10), 19% (P=.41), and 36% (P=.11) for subjects without prior myocardial infarction, with prior myocardial infarction, or with interventional procedure(s), respectively. The 27% reduction in fatal and nonfatal myocardial infarction, although not significant, was comparable to that found in statin cardiovascular end point trials.

All-cause mortality was similar between the treatment groups during the treatment phase for the total cohort (5.8% for atorvastatin and 5.7% for placebo) and for both primary prevention (4.6% and 4.3%, respectively) and secondary prevention subjects (10.3% and 10.7%, respectively).

Adverse events occurred with similar frequency in both treatment groups for the total, primary prevention, and secondary prevention groups. Serious adverse events were experienced by 37.7% of the atorvastatin group and 35.4% of the placebo group.

Despite the lack of reduction in the composite end point of the study, the authors stated that the results "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."

The majority of recent studies have demonstrated a significant coronary heart disease (CHD) benefit of treating individuals with type 2 diabetes with or without prior CHD.

Their results may have differed, the authors stated, because of the study's overall design, the types of subjects recruited, the nature of the primary end point, and the protocol changes required because of changing treatment guidelines.

Case in point, with respect to the quality of the end point, the 15% event rate in the placebo group may have been inflated by the inclusion of hospitalization for angina pectoris and interventions, both of which were frequently recorded in the primary composite end point. This may have diluted the atorvastatin effect, which is evident in the clinical end points of fatal and nonfatal myocardial infarction and in the 28% reduction in CHD death and nonfatal myocardial infarction in the secondary prevention cohort, within the range of that for other secondary prevention trials.

SOURCE Knopp RH, d'Emden M, Smilde JG, Pocock SJ, on behalf of the ASPEN Study Group. 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;29:1478–1485.