Stockholm -- For the first time, a randomized, double-blind, placebo-controlled trial has demonstrated that treating lipid abnormalities with fenofibrate reduces the progression of atherosclerosis by up to 40% in patients with type 2 diabetes. Results of the Diabetes Atherosclerosis Intervention Study, DAIS, have just been presented here to the XIIth International Symposium on Atherosclerosis.

The international trial involved 11 clinical sites in Canada, Finland, France, and Sweden. The study randomized 211 patients to placebo and 207 to fenofibrate, 200 mg daily in its micronized form. All patients received treatment for at least 3 years with regular lipid evaluation. The study population was 40 to 65 years of age with normal to mildly abnormal lipid levels, a lipid profile typical of type 2 diabetes. All patients had good glycemic control. The study included both men and women, with and without previous coronary disease. All patients received a coronary angiogram at baseline and again at the conclusion of the study.

The study was developed and conducted by independent investigators in collaboration with the World Health Organization. The primary aim of the study was to determine, by coronary angiography, whether the correction of lipid abnormalities in type 2 diabetes would alter the progression or regression of coronary atherosclerosis.

Atherosclerosis is the most common complication of diabetes, particularly in type 2. The risk of a coronary event is 3 to 4 times higher in type 2 diabetics than in non-diabetics. Myocardial infarction is the primary cause of mortality and morbidity.

Protection Against Atherosclerotic Progression

Dr George Steiner, the study's project director (University of Toronto, Canada) said that in the treated group of diabetic patients, compared to the placebo group, "there was a 40% reduction in the degree of stenosis." He said these findings indicate that "a distinct and significant benefit was achieved in the individuals who were treated with fenofibrate."

"Fenofibrate reduced progression by 40% in the angiographic parameters considered to reflect focal disease," Steiner elaborated. "There was a reduction in the deterioration of the diffuse disease, mean segment diameter, but the trend was not significant."

Although the study was not powered to assess clinical endpoints, in the treated group there was as well a 23% reduction in the combined endpoints of death, myocardial infarction, angioplasty, and coronary artery bypass graft surgery.

Mechanism of Protection

The study found that in diabetic patients, the higher a patient's triglycerides, the higher the total cholesterol, the higher the LDL cholesterol, and the lower the HDL cholesterol, the greater was the chance of notable progression of coronary artery disease.

These lipid findings help to explain fenofibrate's protective effect, as the study also found that treatment with this drug produced an average reduction of 10% in total cholesterol, 6% reduction in LDL, 6% increase in HDL, and about a 30% reduction in triglycerides.

The Importance of HDL

Dr Frank Sacks (Harvard Medical School, Boston) emphasized the importance of HDL as an independent risk factor for coronary heart disease. He said that an increase in HDL is predictive of a reduction in severity of coronary disease in many clinical trials. He suggested the treatment of diabetes needs to shift from glycemic control to control of lipid abnormalities, particularly HDL.

As a result of the DAIS findings, Steiner said he hopes clinicians will become "much more aggressive about the treatment of lipid abnormalities in individuals with diabetes." He called on physicians to measure lipid levels in individuals with diabetes on an annual basis, even when the levels are normal. He said that when the levels are minimally abnormal, they should be attended to by lifestyle measures, or if lifestyle measures fail, by active medication.

Dr Philip Barter (The University of Adelaide, Australia) said, "We must measure HDL. All of the evidence tells us that HDL is at least as important as LDL." There is now the prospect of achieving benefits by targeting HDL just as has been seen with statins attacking LDL, he explained. He said clinicians should "at least start universally measuring the HDL as well as the LDL, and then take notice of it." Barter's advice to physicians is "to tailor the medication to the lipid disorder."

Pat Phillips
www.athero.org