Moderate Dose, Three-Drug Therapy With Niacin, Lovastatin, and Colestipol to Reduce Low-Density Lipoprotein Cholesterol <100 mg/dl in Patients With Hyperlipidemia and Coronary Artery Disease

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Abstract

The efficacy, safety, and tolerability of a moderate dose, 3-drug lipid-lowering regimen were evaluated among 29 male patients with hyperlipidemia and coronary artery disease. In an initial 12-month phase, regular niacin, 500 mg qid, lovastatin, 20 mg bid, and colestipol, 10 g/bid, were given with dose adjustment for lipid targets and side effects. This was followed by 2 random sequence crossover phases (8 months each) alternating regular niacin with a polygel controlled-release formulation of niacin for use in this regimen. Lipid, lipoprotein, apoprotein, and clinical chemistry determinations were obtained at baseline, during the initial phase, at the 2 crossover phases, and at 6 weeks after therapy. A final questionnaire queried specific side effects and overall preferences. Low-/high-density lipoprotein (LDL/HDL) changed from means of 215/46 mg/dl at baseline, to 94/59 mg/dl after run-in, to 85/52 mg/dl after 8 months of controlled-release niacin, and to 98/56 mg/dl after 8 months of regular niacin (regular niacin vs controlled-release niacin, p <0.005/<0.05). The target of LDL ≤100 mg/dl was achieved at 8 months by 83% of these patients with controlled-release niacin and by 52% with regular niacin (p <0.01). Compliance was 95% with controlled-release niacin versus 85% with regular niacin (p <0.001). The controlled-release niacin and regular niacin regimens did not differ in terms of uric acid, glucose, insulin, or asparate aminotransferase levels. Overall, 21% of patients called the 3 drugs “very easy” and 72% “fairly easy” to take. The controlled-release niacin-containing regimen was preferred by 21 patients and the regular niacin by 4. In conclusion, these regimens achieve striking lipid changes among hyperlipidemic patients. Controlled release is the preferred niacin preparation in terms of LDL reduction, compliance, patient preference, and achieving the National Cholesterol Education Program guideline of LDL ≤100 mg/dl. The 2 niacin preparations did not differ in evidence of toxicity.

Section snippets

Patient Group

Thirty-one consecutive patients were enrolled for a comparison of the polygel controlled-release and regular niacin. All had been participants in the Familial Atherosclerosis Treatment Study (FATS) trial.[3] After its completion, they elected to continue for another 30-month cycle using an open-label regimen that combined 3 approved drugs given at the following target doses: lovastatin 20 mg bid, colestipol 10 g bid, and niacin 500 mg qid. All were men ≤65 years old at high risk for future

Baseline Characteristics

Of 31 patients randomized, 2 left the study during the 12-month run-in phase due to time conflict. Twenty-nine patients completed the 32-month study (Table 1).

Lipid and Clinical Laboratory Response

These data are presented in Table 2. During the 12-month dose-finding period, all 3 drugs were adjusted to achieve target cholesterol levels and minimize side effects. At 12 months prescribed dosages averaged 2.3 ± 0.8 g/day for regular niacin, 38 ± 8 mg/day for lovastatin, and 19.5 ± 3.4 g/day for colestipol. After 12 months on this

Discussion

Overall, the 3-drug regimen proved extremely effective and well-tolerated, in part due to close follow-up and careful patient education, and in part due to a moderate dosing schedule for each of the 3 drugs. Significant differences between the 2 niacin preparations (in compliance, total and LDL cholesterol and LDL/HDL ratio reduction, flushing, and overall preference) favored the controlled-release preparation although it was somewhat less effective in raising HDL.

This experience stands in

Acknowledgements

The efforts of Robert P. Kelly in preparing this manuscript are greatly appreciated. The pharmaceutical supplies were provided by Merck Research Laboratories, Inc., West Point, Pennsylvania; Upjohn Co., Inc., and Upsher-Smith, Inc., Minneapolis, Minnesota.

This study was supported in part by grants R01 HL 19451, PO 1 HL 30086, 35816, P30 DK 17047, and R01 HL 42419 from the National Heart, Lung, and Blood Institute and National Institutes of Health, Bethesda, Maryland; in part by the University

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