Diabetes Atherosclerosis Intervention Study - DAIS

Description:

The DAIS trial was designed to assess whether correcting lipoprotein abnormalities in patients with type 2 diabetes would decrease the rate of angiographic progression of coronary artery disease (CAD).

Hypothesis:

In patients with type 2 diabetes and dyslipoproteinemias, treatment with fenofibrate would reduce the angiographic progression of CAD compared to placebo-controlled patients.

Study Design

Study Design:

Patients Screened: 731
Patients Enrolled: 418
Mean Follow Up: 39 months
Mean Patient Age: 40-65
Female: 27

Patient Populations:

Men and women with type 2 diabetes aged 40-65 years, and lipid and diabetes eligibility assessed off lipid-lowering agents and on NCEP Step 1 diet.

• Lipid criteria: total cholesterol to HDL-cholesterol ratio of four or more, plus either an LDL-cholesterol concentration of 135–174 mg/dl and triglyceride concentration of 461 mg/dl or less, or a triglyceride concentration of 151–256 mg/dl and LDL-cholesterol 175 mg/dl or less.

• Diabetes criteria: fasting glucose off treatment of 140 mg/dl or a plasma glucose concentration of 198 mg/dl two hours after a 75 gm oral glucose load; or on treatment with glucose-lowering drugs.

Exclusions:

Diagnosis of diabetes after age 35; history of ketoacidosis; inadequate glycemic control (HgbA1c >170% of lab’s upper limit of normal); less than one visible lesion on angiogram; or percutaneous coronary intervention within six months

Primary Endpoints:

Mean coronary artery segment diameter

Secondary Endpoints:

Average minimum lumen diameter, and average percent diameter stenosis

Drug/Procedures Used:

Fenofibrate (200 mg/day) versus placebo control for at least three years

Concomitant Medications:

Standard care with treatment of diabetes per physician’s discretion, and National Cholesterol Education Program (NCEP) Step 1 diet for all patients

Principal Findings:

A total of 418 patients were enrolled. The two arms were well-balanced. Overall, half of the study patients had a history of prior CAD. As compared to the placebo arm, total and low-density lipoprotein (LDL) cholesterol as well as triglycerides significantly decreased in the fenofibrate arm, and high-density lipoprotein (HDL) significantly increased (p<0.001 for each).

Fenofibrate treatment was associated with a smaller decrease in minimum lumen diameter (-0.06 vs. -0.10 mm, p=0.029), smaller increase in percentage diameter stenosis (2.11% vs. 3.65%, p=0.02), and nonsignificantly smaller decrease in the primary endpoint of mean segment diameter (-.06 vs. -0.08 mm, p=0.171). There was a mild correlation between the angiographic changes and the changes in lipid profiles; the effect of fenofibrate was similar across all subgroups.

Interpretation:

Post-hoc subgroup analyses of lipid prevention trials have indicated that lipid-lowering therapy in diabetic patients can decrease CAD progression. The DAIS study was a prospective study examining the effect of fenofibrate therapy compared to placebo in reducing angiographic disease progression in type 2 diabetic patients.

Although the primary endpoint was not significantly different between treatment and placebo groups, the reduced rates of disease progression measured by parameters of focal disease progression including percent diameter stenosis and minimum lumen diameter suggests that lipid-lowering therapy in diabetics can result in beneficial effects such as the slowing of focal coronary atherosclerotic disease.

References:

Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet 2001;357:905-10.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Lipid Metabolism, Nonstatins

Keywords: Fenofibrate, Coronary Artery Disease, Dyslipidemias, Cholesterol, LDL, Diabetes Mellitus, Type 2, Hypolipidemic Agents, Cholesterol, HDL, Constriction, Pathologic, Triglycerides, Disease Progression


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