Abstract

The Collaborative AtoRvastatin Diabetes Study (CARDS) is the first large primary prevention study to focus specifically on the role of a statin in patients aged 40-75 years with type 2 diabetes, but no signs or symptoms of pre-existing vascular disease and who had only average or below average cholesterol levels. The trial was a prospective double-blind randomised trial with 2383 type 2 diabetic subjects randomised to either 10-mg atorvastatin daily or placebo. Originally designed to run for 5 years, the trial was terminated over a year early in June 2003 on account of a clear benefit demonstrated for the intervention group. Over half of patients had a low-density lipoprotein cholesterol (LDL-C) below 3.3 mmol/l at entry and a quarter had an LDL-C <2.6 mmol/l. Atorvastatin 10 mg reduced LDL-C by 40% (1.2 mmol/l) on average. Results at 4 years showed a 37% relative risk reduction (p <0.001) for atorvastatin 10 mg in the primary endpoint (acute coronary heart disease death, fatal or non-fatal myocardial infarction, unstable angina requiring hospital admission, resuscitated cardiac arrest, coronary revascularisation procedures and stroke). Among the secondary endpoints, total mortality was reduced by 27% (p=0.05), acute coronary events by 36%, coronary revascularisation by 31% and stroke by 48%. The same magnitude of benefit was observed among patients with LDL-C above or below 3 mmol/l. Results observed were against a background where 9% of placebo patients had been permitted to start statin therapy after enrolment and 15% of patients on active treatment had discontinued atorvastatin. The true benefit of the intervention is therefore probably around 25% greater than the intention to treat analysis reports.