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HDL-Atherosclerosis Treatment Study - HATS
Description:
HATS was designed to determine the effect of a simvastatin-niacin combination, with or without antioxidants, and antioxidants alone, on angiographic stenosis and cardiovascular events.
Hypothesis:
Lipid-altering and antioxidant therapy provide independent and additive benefits for patients with coronary artery disease and low HDL levels.
Study Design
Study Design:
Patients Screened: 454
Patients Enrolled: 160
NYHA Class: not reported
Mean Follow Up: 3 years
Mean Patient Age: not reported
Female: 13
Mean Ejection Fraction: not reported
Patient Populations:
Clinical coronary disease (defined as previous myocardial infarction, coronary interventions, or confirmed angina). At least three stenoses >=30% or one stenosis >=50%. Low levels of HDL cholesterol (<=35 mg per dL in men and <=40 mg per dL in women). LDL cholesterol levels of <=145 mg per dL. Triglyceride levels <400 mg per dL.
Exclusions:
Prior coronary bypass surgery, severe hypertension, recent gout, liver, thyroid, or kidney disease, uncontrolled diabetes.
Primary Endpoints:
Mean change in percent stenosis in the most severe lesion in each of the nine proximal coronary segments from baseline to final arteriogram.
Secondary Endpoints:
Mean change in luminal diameter in proximal lesions and all lesions. Time to the first of the following events: death from coronary causes, nonfatal myocardial infarction, stroke, or revascularization for worsening ischemia.
Drug/Procedures Used:
One of four regimens: 1) simvastatin plus niacin, 2) antioxidants, 3) simvastatin-niacin plus antioxidants, 4) or placebos Simvastatin dosing was 10 mg/day for patients with an LDL <=110 mg per dL and 20 mg/day for patients with an LDL >110 mg per dL. The dose was increased by 10 mg/day for patients with an LDL >90 during the first year and reduced by 10 mg/day for patients with an LDL <40 at any time during the study. Slow-release niacin was increased from 250 mg twice daily to 1000 mg twice daily at four weeks. Patients whose HDL cholesterol levels had not increased by >=5 mg per dL at 3 months, >= 8 mg per dL at 8 months, and >=10 mg per dL at 12 months were switched to crystalline niacin (dose gradually increased to 3 g per day to meet the target levels). Antioxidants given twice daily included total daily dose of 800 IU vitamin E, 1000 mg vitamin C, 25 mg beta carotene, and 100 microg selenium.
Concomitant Medications:
Counseling during each visit, emphasizing weight loss and consumption of monounsaturated fats.
Principal Findings:
The mean levels of LDL and HDL cholesterol did not change in the antioxidant group or the placebo group; LDL was lower by 42% (p<0.001) and HDL was higher by 26% (p<0.001) in the simvastatin-niacin group; similar changes occurred when antioxidants were added to the regimen. Plasma vitamin concentrations increased significantly in the patients who received active vitamin therapy. The average stenosis progressed by 3.9% in the placebo group, 1.8% in the antioxidant group (p=0.16 for the comparison with the placebo group), 0.7% in the simvastatin-niacin plus antioxidant group (p=0.004), and regressed by 0.4% in the simvastatin-niacin alone group (p<0.001). Clinical cardiovascular events occurred in 24% in placebo group, 21% in the antioxidant group, 14% in the simvastatin-niacin plus antioxidant group, and 3% in the simvastatin-niacin alone group (p=0.03 vs placebo).
Interpretation:
Simvastatin plus niacin was associated with significant clinical and angiographic benefits in patients with coronary disease and low HDL levels. The rate of major clinical events was 90 percent lower with the simvastatin-niacin combination than in the placebo group. The benefit of antioxidant vitamins for coronary disease prevention was not evident; no additional benefit was observed with its concommitant use, and event rates and disease progression were similar to placebo when antioxidants alone were used. These findings concur with the results of several large negative trials of vitamins (HOPE, GISSI-Prevention, Physicians Health Study).
References:
N Engl J Med 2001;345:1583-92.
Keywords: Coronary Artery Disease, Myocardial Infarction, Vitamin E, beta Carotene, Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Constriction, Pathologic, Simvastatin, Selenium, Hypolipidemic Agents, Cholesterol, HDL, Niacin, Triglycerides, Disease Progression
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