Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study

Background Atherosclerosis is the most common complication of diabetes. Cor rection of hyperglycaemia helps to prevent microvascular complications but has little effect on macrovascular disease. Post-hoc analyses of diabetic s ubpopulations in lipid intervention trials suggest that correction of lipop rotein abnormalities will lead to a decrease in coronary-artery disease. Th e Diabetes Atherosclerosis Intervention Study (DAIS) was specifically desig ned to assess the effects of correcting lipoprotein abnormalities on corona ry atherosclerosis in type 2 diabetes. Methods 731 men and women with type 2 diabetes were screened by metabolic a nd angiographic criteria. 418 were randomly assigned micronised fenofibrate (200 mg/day) or placebo for at least 3 years. They were in good glycaemic control (mean haemoglobin A(10) 7.5%), had mild lipoprotein abnormalities, typical of type 2 diabetes, and at least one visible coronary lesion. Half had no previous clinical coronary disease. Initial and final angiograms fol lowed a standard protocol and were analysed by a computer-assisted quantita tive approach. Missing data for the primary endpoints (minimum lumen diamet er, mean segment diameter, and mean percentage stenosis) were imputed. Anal yses were by intention to treat. Findings Total plasma cholesterol, HDL-cholesterol. LDL-cholesterol, and tr iglyceride concentrations all changed significantly more from baseline in t he fenofibrate group (n=207) than in the placebo group (n=211). The fenofib rate group showed a significantly smaller increase in percentage diameter s tenosis than the placebo group (mean 2.11 [SE 0.594] vs 3.65 [0.608]%, p=0. 02), a significantly smaller decrease in minimum lumen diameter (-0.06 [0.0 16] vs -0.10 [0.016] mm, p=0.029), and a non-significantly smaller decrease in mean segment diameter (-0.06 [0.017] vs -0.08 [0.018] mm, p=0.171). The trial was not powered to examine clinical endpoints, but there were fewer in the fenofibrate group than the placebo group (38 vs 50). Interpretation DAIS suggests that treatment with fenofibrate reduces the an giographic progression of coronary-artery disease in type 2 diabetes. This effect is related, at least partly, to the correction of lipoprotein abnorm alities, even those previously judged not to need treatment.