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Treating Low-HDL, High-Triglyceride Patients.

ATLANTA -- The combination of a low dose statin and moderate-dose niacin achieves "striking" lipid improvements in patients with a low HDL cholesterol level and high triglycerides, Dr. B. Greg Brown reported at a satellite conference that was sponsored by Novartis Pharmaceuticals Corp. and held in conjunction with the annual scientific sessions of the American Heart Association.

The statin-niacin combination is but one of five broad therapeutic strategies available for use in patients with a low HDL level. Based on interim data from his ongoing clinical trial, combination therapy appears to be a particularly promising approach, said Dr. Brown, professor of medicine at the University of Washington, Seattle.

Sixteen months into his planned 3-year angiographic study of patients who have coronary artery disease along with a mean baseline LDL of 132 mg/dL, an HDL of 32 mg/dL, and plasma triglycerides of 188 mg/dL, the lipid results with the statinniacin combination are as follows: a robust 49% reduction in LDL, a 31% rise in HDL, and a 26% decline in triglycerides.

All this has been achieved using an average daily dosage of just 10mg of simvastatin coupled with 3.2 g of immediate-release niacin. Angiographic outcomes in the study will be available next fall, Dr. Brown said.

Epidemiologic data suggest that for every 1% increase in HDL, a patient's risk of a coronary event is reduced by 3%. In addition to such nonpharmacologic methods of enhancing HDL as exercise, weight loss, and alcohol, there are four pharmacologic strategies beyond manipulation of the LDL to HDL ratio via therapy with a low-dose statin and a moderate dose of niacin. These pharmacologic strategies are:

* Lower the LDL. This is the strategy backed by the best evidence of clinical benefit to date. The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) demonstrated that lowering LDL with statin and/ or resin therapy in patients who have a low HDL level is surprisingly effective at preventing coronary events.

This result was unexpected, he said, because many patients with a low HDL level have a normal or even desirably low LDL level.

Nearly all of the clinical benefit in terms of reduced event rates in AFCAPS / TexCAPS occurred in patients in the lowest third of HDL distribution at baseline, those with an HDL below 34 mg/dL.

* Boost the HDL. This is achievable using niacin and/or fibric acid derivatives. The recently reported 2,500-patient Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT) used these drugs to achieve a 7% rise in HDL level and a 26% drop in triglycerides.

This translated into a 26% reduction in the combined end point of coronary death, nonfatal MI, or stroke--all achieved with no change in LDL (N. Engl. J. Med. 341[6]:410-18, 1999).

* Use antioxidants. HDL contains antioxidants that protect LDL against oxidation. The possibility that a low HDL level is an antioxidant deficiency state that can be effectively countered via an antioxidant cocktail of vitamins C, [beta]-carotene, and selenium is now under study by Dr. Brown and other investigators.

* Bear down on diabetes. Improved glycemic control in diabetic patients results in lower triglycerides along with an increase in HDL. However, the central adiposity and insulin resistance component of diabetes isn't effectively treated by improved glycemic control; these abnormalities help maintain low HDL.

"You're not going to get an HDL of 25 mg/dL up to 45 with improved glycemic control, but you will get a 25 to 35," according to Dr. Brown.
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Publication:Family Practice News
Article Type:Brief Article
Geographic Code:1USA
Date:Feb 1, 2000
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