Primary Prevention of Cardiovascular Disease With Atorvastatin in Type 2 Diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): Multicentre Randomised Placebo-Controlled Trial

Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HAW, Livingstone SJ, Thomason MJ, Mackness MI, Charlton-Menys V, Fuller JH, on behalf of the CARDS investigators. Lancet. 2004;364:685-696.

The purpose of the Collaborative Atorvastatin Diabetes Study (CARDS) was to determine the efficacy of atorvastatin 10 mg/day compared with placebo in the primary prevention of cardiovascular disease in patients with type 2 diabetes who had no history of cardiovascular disease and high low-density lipoprotein cholesterol (LDL-C) levels. Because of positive study results, the trial was ended 2 years early.

In total, 2838 patients with type 2 diabetes (aged 40–75 years) were randomized to treatment with atorvastatin 10 mg/day (n=1428) or placebo (n=1410). Patients were recruited from 132 centers throughout the UK and Ireland. Entry criteria included a history of hypertension, retinopathy, or albuminuria, or currently smoking; and no history of cardiovascular disease (myocardial infarction, angina, coronary vascular surgery, cerebrovascular accident, or severe peripheral vascular disease). Upon study entry, patients had a mean LDL-C ≤4.14 mmol/L and fasting triglycerides ≤6.78 mmol/L.

Primary end point was time to first cardiovascular event, defined as an acute coronary heart disease event (myocardial infarction including silent infarction, unstable angina, resuscitated cardiac arrest, or death due to acute coronary heart disease), coronary revascularization procedure, or stroke. Secondary end points were the effect of atorvastatin on total mortality and any acute cardiovascular end point (hospital-verified). Patients were followed for a median of 3.9 years.

Overall, there was a 37% reduction in major cardiovascular events in patients treated with atorvastatin compared with placebo (P=.001); 83 patients in the atorvastatin group had at least 1 major cardiovascular event compared with 127 patients in the placebo group. Treatment with atorvastatin 10 mg/day over 4 years would therefore be expected to prevent 37 major vascular events per 1000 individuals treated with atorvastatin. There was a 36% reduction in acute coronary heart disease events, a 31% reduction in coronary revascularizations, and a 48% reduction in stroke in patients treated with atorvastatin compared with placebo-treated patients. In terms of secondary end points, there was a 27% reduction in death from any cause and a 30% reduction in any acute cardiovascular disease event in the atorvastatin-treated group compared with the placebo-treated group.

This study demonstrates that atorvastatin 10 mg/day is a safe and efficacious treatment for the primary prevention of cardiovascular disease events in patients with type 2 diabetes with no previous history of cardiovascular disease and high LDL-C levels. These findings have important implications for the use of statins as preventive treatment for macrovascular complications in type 2 diabetes as well as LDL-C treatment targets, suggesting current treatment targets of 2.5–2.6 mmol/L could be lower.