Does Atorvastatin Prevent Cardiovascular Events Among Diabetics?

In this randomized trial, the formal answer was no, but several aspects of the study might have blunted its ability to show a significant benefit for atorvastatin.

Patients with diabetes are at higher risk for cardiovascular events than are nondiabetics. In a multinational, industry-sponsored trial, researchers randomized 2410 patients with type 2 diabetes to daily atorvastatin (10 mg) or placebo and assessed the effect of treatment on subsequent cardiovascular events. All patients had either known coronary artery disease plus LDL cholesterol levels of 140 mg/dL, or no history of CAD plus LDL levels of 160 mg/dL. During the second half of the study, the National Cholesterol Education Program (NCEP) issued new cholesterol management guidelines and lowered LDL targets. As a consequence, it was recommended that the study medication be discontinued among all patients with histories of CAD and in all those without histories of CAD who had reached a study endpoint. Thus, only 68% of atorvastatin subjects and 58% of placebo subjects were taking study medications at completion, and open-label lipid-lowering therapy was prescribed to some patients in both groups.

Median follow-up was 4 years. Mean LDL cholesterol levels were reduced by 29% in the atorvastatin group compared with the placebo group. No significant difference was noted between groups in the incidence of the primary endpoint, a composite of several cardiovascular events that included myocardial infarction and stroke. Atorvastatin lowered risk for fatal and nonfatal and MI by 19% among diabetics without histories of CAD and by 36% among those with histories of CAD, but both risk reductions failed to reach statistical significance.

Comment: In this study, a 29% reduction in LDL levels with atorvastatin compared with placebo failed to lower the incidence of cardiovascular events among diabetics. This result could be attributable to the relatively low dose of atorvastatin used, a relatively low risk for cardiovascular disease during the early years after diagnoses of diabetes are established, and the protocol change during the study (which resulted in some placebo patients receiving statin therapy). Although the 36% reduction in risk for MI among diabetics with histories of CAD did not reach statistical significance, this particular finding is difficult to ignore and supports current NCEP guidelines.

— Jamaluddin Moloo, MD, MPH

Citation(s):

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; 29:1478-85.