Arterial Disease Multiple Intervention Trial - ADMIT
The goal of the trial was to evaluate the efficacy and safety of lipid modification with niacin among patients with diagnosed peripheral arterial disease with or without diabetes.
Patients Screened: 1,171
Patients Enrolled: 468
Mean Follow Up: Five years
Mean Patient Age: Mean age 66 years
Reduced ankle brachial index <0.85 or a history of prior lower-extremity revascularization
Poorly controlled diabetes (HbA1c >9.0%), history of diabetic ketoacidosis or coma, renal disease, liver disease, gout, hyperuricemia, peptic ulcer disease, history of myositis, untreated hypothyroidism, hypertriglyceridemia (>400 mg/dl), or LDL level not likely to be controlled by niacin and/or pravastatin (baseline LDL >190 mg/dl)
Patients were randomized to niacin (3000 mg/d or maximum tolerated dosage) (n=64 with diabetes; n=173 without diabetes) or placebo (n=61 with diabetes; n=170 without diabetes) for up to 60 weeks. The first 12 weeks was an open-label run-in phase, and the remaining 48 weeks were double-blind. Patients were also randomized to antioxidant vitamins and low-dose warfarin, or corresponding placebo treatments, in a 2x2x2 factorial design. This article presents information on the 125 patients who at the first study visit met the criteria for diabetes, defined as history of diabetes treated by diet or medication or a hemoglobin A1c (HbA1c) level >7% at the baseline visit.
Slightly more than one-quarter of the patients in the trial were diabetic (27%, 125/468). Baseline high-density lipoprotein cholesterol (HDL-C) was lower in diabetics compared with nondiabetics (39 mg/dl vs. 42 mg/dl, p=0.01). When comparing baseline characteristics by treatment groups, characteristics were well balanced with the exception of a slightly older population in the diabetic placebo group compared with the diabetic niacin group (68 vs. 66 years, p=0.04).
HDL-C was increased by 29% in the niacin group (p<0.001 compared with placebo) in both patients with and without diabetes, and low-density lipoprotein cholesterol (LDL-C) was decreased by 8% and 9% in the niacin group (p<0.001 compared with placebo) in diabetics and nondiabetics, respectively. Triglycerides were also lowered by 23% and 28% in the niacin group (p<0.001 compared with placebo) in diabetics and nondiabetics, respectively. Glucose levels increased in the niacin group in patients with and without diabetes (diabetics: 8.1 for niacin vs. -8.7 mg/dl for placebo, p=0.04; nondiabetics 0.5 for niacin vs. 6.3 mg/dl for placebo, p<0.001).
HbA1c levels did not change from baseline to follow-up in diabetic patients in the niacin group, but did decrease in diabetics in the placebo group (0% vs. -0.3%, p=0.04). There was no difference in HbA1c in nondiabetics between the niacin group versus placebo groups (0.5% vs. 0.4%, p=0.38). Study drug discontinuation in the niacin group did not differ in diabetics versus nondiabetics (23% vs. 16%, p=0.20), nor did it differ between niacin versus placebo among diabetics (23% vs. 18%, p=0.46).
Among patients with diagnosed peripheral arterial disease with or without diabetes, treatment with niacin was associated with an increase in HDL-C and a reduction in LDL-C and triglycerides compared with placebo in both diabetics and nondiabetics.
Niacin use had been discouraged in patients with diabetes, due in large part to nonrandomized studies that reported worsening glycemic control in patients treated with niacin. While the present randomized study did confirm increases in glucose associated with niacin therapy, the increases did not appear to result in increases in study drug discontinuation. However, it should be noted that diabetic patients in the present trial had stable, controlled diabetes, and uncontrolled diabetics were excluded.
Elam MB, Hunninghake DB, Davis KB, et al. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: A randomized trial. Arterial Disease Multiple Intervention Trial. JAMA 2000;284:1263-70.
Keywords: Vitamins, Hemoglobin A, Glycosylated, Cholesterol, Ankle Brachial Index, Blood Glucose, Warfarin, Peripheral Arterial Disease, Niacin, Diet, Triglycerides, Diabetes Mellitus
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