It is well established that type 2 diabetes increases the risk of stroke, myocardial infarction and other types of heart diseases. It is also established in several secondary prevention trials that statins reduce major cardiovascular events through lowering the level of lipids in blood. These include the HPS trial, the 4S trial and the CARE trial. The role of statin in primary prevention of CHD was only recently established in the Collaborative Atorvastatin Diabetes Study (CARDS) trial.
The objective of the CARDS trial is to access the effectiveness of atorvastatin 10mg daily in the primary prevention of cardiovascular disease in patients with type 2 diabetes. The trial involved 2838 patients, randomized into 2 arms: the placebo arm and the atorvastatin arm. The patients were followed for 4 years. 132 diabetes centers in UK and Ireland were involved in the study.
The inclusion criteria for the trial are (i) patients with Type 2 diabetes and one or more cardiovascular risk factors and (ii) their LDL is less than 4.14 mmol/L and their triglycerides is less than 6.78 mmol/L and (iii) patients are without a personal history of cerebrovascular, peripheral vascular and cardiovascular diseases.
The outcomes of the study are
(i) time to first event of non-fatal myocardial infarction, unstable angina, CHD death, stroke, coronary revascularization
(ii) acute coronay events
(v) all-cause mortality
The trial was terminated 20 months earlier than planned since the statin arm shows a significant reduction in mortality and cardiovascular events. It would be unethical to not giving statin to the placebo arm based on the findings. Overall, there was a 37% reduction in major CVD events, 48% reduction in stroke, and 27% reduction in all-cause mortality. More importantly, the reductions were observed across all ages, genders, lipid concentrations. There were also no differences between the placebo arm and the statin arm in term of liver and muscle diseases, which are major side effects of statin. Thus, atorvastatin 10 mg is safe for diabetes patients.
The remaining questions are whether the same positive effects will be observed for younger patients with diabetes, whether there is an optimal LDL level for patient or what are the benefits by combining statin with other drugs.
Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atovastatin Diabetes Study (CARDS). Lancet 2004;364:685-96.