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Niacin and Atherosclerotic Cardiovascular Disease



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Am Fam Physician. 1999 Apr 1;59(7):1959-1961.

The easily recognizable side effects of niacin seem to have somewhat overshadowed its usefulness in the treatment of hyperlipidemia. To examine the usefulness of niacin in the treatment of atherosclerotic cardiovascular disease, Guyton reviewed data from six major clinical trials in which cardiovascular events were end points. These trials were the Coronary Drug Project, the Stockholm Ischemic Heart Disease Secondary Prevention Study, the Cholesterol-Lowering Atherosclerosis Study, the Familial Atherosclerosis Treatment Study, the Harvard Atherosclerosis Reversibility Project and an unnamed study conducted at the University of California–San Francisco.

The first landmark study that used niacin was the multicenter Coronary Drug Project (CDP). Published in 1975, this study was the only one that used niacin monotherapy to affect cardiovascular endpoints. A total of 8,341 men with a previous myocardial infarction were recruited for the six-year randomized trial. Niacin in a dosage of 1 g three times daily was found to decrease cholesterol levels by 10 percent and triglyceride levels by 26 percent. Recurrent nonfatal myocardial infarction was decreased by 27 percent. The frequency of cerebrovascular events was decreased by 26 percent. The cardiovascular mortality risk was also decreased, to a small degree.

The Stockholm Ischemic Heart Disease Secondary Prevention Study was a five-year randomized placebo-controlled trial of 555 consecutive survivors of myocardial infarction. Results of this study demonstrated decreased total and cardiac mortality among men taking a combination of niacin, 1 g three times daily, and clofibrate, 1 g twice daily. Cholesterol levels decreased by 13 percent and baseline triglyceride levels by 19 percent in the treated patients. Total mortality was decreased by 26 percent, which is considered to be the most important finding of this study.

The Cholesterol-Lowering Atherosclerosis Study (CLAS) was a randomized, placebo-controlled trial of 162 men aged 40 to 59 years who had undergone coronary artery bypass surgery. Cardiovascular endpoints were measured by coronary angiography. Follow-up was for four years in 103 of the men (CLAS II). Patients received combination therapy with niacin and colestipol. In CLAS I, 39 percent of the men receiving niacin and colestipol had progresion of disease, compared with 61 percent of the men receiving placebo. In LAS II, 48 percent of the treated group had progression, compared with 85 percent of the placebo group. Disease regression was noted in 16 percent of the CLAS I subjects and 18 percent of the CLAS II subjects receiving the cholesterol-lowering therapy. With placebo, regression was noted in 2 percent and 6 percent, respectively, of the CLAS I and CLAS II patients,

In the Familial Atherosclerosis Treatment Study (FATS), 146 men with documented coronary artery disease and apolipoprotein B levels of more than 125 mg per dL were included in the 30-month study. Patients were randomly assigned to treatment with 4 g of niacin plus 30 g of colestipol per day or 40 mg of lovastatin plus 30 g of colestipol per day. Patients receiving the combination of niacin and colestipol had a higher increase in high-density lipoprotein (HDL) levels than those receiving lovastatin and colestipol. Regression of coronary stenosis was small and of questionable clinical significance. However, the number of cardiovascular events was significantly lower in the intensive treatment groups: two events among 48 patients receiving niacin and colestipol, three events among 46 patients receiving lovastatin and colestipol and 11 events in 52 patients receiving conventional therapy.

The University of California–San Francisco study included 72 patients with familial hypercholesterolemia. In this two-year, placebo-controlled study, patients were assigned to intensive treatment with niacin plus colestipol or lovastatin (when lovastatin became available). Angiographic progression occurred in the control group, but lesions regressed in the treated group. Regression of atherosclerosis occurred despite elevated low-density lipoprotein levels.

The Harvard Atherosclerosis Reversibility Project (HARP) evaluated whether stepped therapy with four lipid-lowering drugs, including niacin, would affect progression of coronary lesions in patients with normal cholesterol levels. Unlike the other studies, HARP did not demonstrate significant differences in lesion progression or in coronary events. The active treatment group did, however, have 33 percent fewer clinical events than the control group.

The side effects of niacin included flushing, stomach pain, nausea, acute gouty arthritis, and a variety of skin problems such as itching, urticaria, hyperpigmentation and rashes. Other less common adverse symptoms included dysuria, polyuria, anorexia and unexpected weight loss. Niacin can also cause increases in aspartate aminotransferase, alkaline phosphatase, creatine kinase, glucose and uric acid levels.

The author concludes that the results of these clinical studies demonstrate statistically significant benefit from niacin in patients with atherosclerotic disease. Only one of the studies used niacin monotherapy, but this study was by far the largest. The author also points out that the benefits were observed in studies that did not necessarily recruit patients with dyslipidemia. Niacin may be most useful in patients with high triglyceride, low HDL cholesterol and high lipoprotein(a) levels.

Guyton JR. Effect of niacin on atherosclerotic cardiovascular disease. Am J Cardiol. December 17, 1998;82:18U–23U.

editor's note: A new extended-release niacin (Niaspan) allows a once-daily dosage. Used as monotherapy or in combination, niacin has been found to reduce LDL cholesterol levels and increase HDL cholesterol levels. Triglyceride and lipoprotein(a) levels can also be significantly reduced. The extended-release niacin frequently causes flushing, but this side effect can be reduced with concomitant aspirin. Flushing often decreases over several months. Elevation of liver enzymes occurs with niacin but hepatotoxity is rare. The combination of sustained-release niacin and a statin appears to be safe and effective as long as the patient is monitored for the development of myopathy and hepatic inflammation.—r.s.

 


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