Drug Topics - November 5, 2007 - (Page 32)

32 DRUG TOPICS NOVEMBER 5, 2007 www.drugtopics.com CONTINUING EDUCATION 2,000 mg in order to achieve the maximum effects of elevated HDL-C. The proper titration begins with the 500-mg dose, which is increased monthly by 500 mg to attain lipid goals. Nicotinic acid therapy should be used as an adjunct to lifestyle modifications when nonpharmacologic measures such as dietary changes, weight loss, and exercise prove inadequate in controlling lipid levels. Contraindications to nicotinic acid products include active liver disease, unexplained elevated liver function tests, active peptic ulcer disease, arterial bleeding, and hypersensitivity to nicotinic acid. Cautious use is warranted in patients with renal dysfunction, excessive alcohol use, elevated uric acid levels or gout, and uncontrolled diabetes. The concern of using niacin in patients with diabetes has risen as a result of reports indicating elevated blood glucose accompanying increased insulin resistance. In the Assessment of Diabetes Control and Evaluation of the Efficacy of Niaspan Trial, the investigators concluded that lower doses of ER niacin (i.e., 1,000 mg and 1,500 mg) are safe and effective options to treat dyslipidemia in patients with Type 2 diabetes. Furthermore, the American Diabetes Association recommends niacin as first-line therapy for raising HDL-C levels and that when appropriate, the increased blood glucose can be overcome by adjusting diabetic therapy and using nicotinic acid in doses of 3 gm or less per day. ticles were reviewed, covering multiple soy preparations broken into three categories: soy protein with isoflavones, soy protein without isoflavones, and isoflavones without soy protein. The authors analyzed studies that assessed numerous cardiovascular biomarkers such as: TC, LDL, HDL, apoA-I, TG, apoB, lipoprotein (a), apoC-III, apoE, C-reactive protein, endothelin, homocysteine, and oxidized LDL. This discussion will be narrowed to the pertinent results regarding HDL-C levels. HDL-C levels were reported in 61 studies. Of these 61 trials, five reported no difference between placebo and soy consumption on HDL-C levels. Of the remaining 56 studies, approximately half of the cohorts consuming soy had a net increase in HDL-C levels compared with the control group, which had one-quarter experiencing no effect on HDL-C levels and the remaining one-quarter actually netting a decrease in HDL-C levels. A meta-analysis of these divergent conclusions regarding HDL-C levels resulted in a net change of +0.6 (95% CI –0.5, +1.8) mg/dl. The interpretation of the confidence interval implies that the increase in HDL-C may not hold true in a broader population. This EPC does indeed suggest that soy consumption may benefit its consumers, at least as far as their LDL and TG levels are concerned, as soy demonstrated reductions in these parameters. Soy-containing supplements should not be recommended for those with clotting disorders, estrogen-positive tumors, or a history of allergic reactions to soy. Despite this report’s extensive review, many questions remain. Which soy products are the most beneficial and in what daily amounts? Which demographics/populations can use soy products to obtain therapeutic effects? Will the introduction of soy into the diet of a patient who is on other lipid-altering therapy still prove beneficial or will the positive lipid effects be nullified with the use of other therapeutic agents? The current results highlight the merit for these answers to be clarified for clinicians who wish to recommend this age-old product for cardiovascular benefits. Other prescription therapies to raise HDL-C levels Other therapies such as statins, fibric acid derivatives, bile acid sequestrants, and cholesterol absorption inhibitors impact HDL-C levels but with varying effects. Statins are predominantly used for their impressive effects on LDL-C; however, they modestly raise HDL-C levels by 5% to 15%. Fibric acid derivatives, including fenofibrate and gemfibrozil, increase HDL-C levels by 10% to 20%, and have the largest impact on this lipid parameter other than niacin. Bile acid sequestrants such as cholestyramine and colesevelam minimally raise HDL-C levels by 3% to 5%, and the cholesterol absorption inhibitor, ezetimibe, raises HDL-C by only 1%. Increases in HDL-C levels can be enhanced through the use of combination therapy with any of these treatment options. Hormone replacement therapies, including estrogen- and estrogen/progestin-containing products, have been shown to improve HDL-C levels in postmenopausal women while providing additive relief of hot flashes. Estrogens promote gene expression that yields protection against the development of heart disease. However, estrogens are also associated with increasing C-reactive protein, a marker for inflammation. Based on current clinical findings, the American Heart Association does not advocate the use of estrogen-containing products specifically for the reduction of cardiovascular disease. Effects of soy on health outcomes Soy is used for multiple purposes, including, but not limited to, weight loss, vasomotor symptoms associated with menopause, osteoporosis, and reducing the risk for cardiovascular disease. Evidence-Based Practice Centers (EPCs) have contracted with the Agency for Healthcare Research and Quality (AHRQ) to provide data on the safe use of complementary alternative medicine, especially in the area of cardiovascular health. In the report “Effects of Soy on Health Outcomes” by the EPC, 61 ar- Therapeutic strategies on the horizon In the fight against cardiovascular disease, HDL-C as a primary therapeutic target seems promising. A recent review by Singh et al. noted 11 therapeutic agents that are in various stages of clinical development. The current agents under investigation can be divided into a few different classes. Therapeutic divisions include CETP inhibitors, peroxisome proliferator-activated receptor (PPAR) agonists, apoA-I mimetics, and novel nicotinic acid formulations. CETP inhibitors. Recall that CETP is a protein that is responsible for transferring cholesteryl esters (CE) from HDL to either LDL or VLDL as well as transferring TG from LDL or VLDL to HDL. Many articles support the theory behind inhibiting CETP as an effective means of increasing circulating levels of HDL-C. It is known that reducing the transfer of CE from TG to HDL-C increases a particular HDL-C subtype, called mature alpha HDL-C. This mature HDL-C subtype has the ability to interact in reverse cholesterol transport in three ways: 1. Mature HDL-C can discard CE through binding with scavenger receptors class B1 (SR-B1) found in hepatocytes and, therefore, become a lipid-poor HDL particle that can return to plaque-laden arteries and remove more CE. http://www.drugtopics.com

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Drug Topics - November 5, 2007 Contents Latebreakers Latebreakers in Depth Letters Rx Care Community Practice 150 Years of American Pharmacy Hospital Practice Pharmacists at Risk Government and Law High-Density Lipoprotein New Products Advertisers Index Classified Viewpoint

Drug Topics - November 5, 2007

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