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Biomedical subjects

Michael H Davidson

Publications and source records attributed to Michael H Davidson.

At least 73 records · Page 4Linked to original sources
PubMed2003

Efficacy of over-the-counter nutritional supplements.

More than 100 million people in the United States report using nutritional supplements. Most people are under the impression that nutritional supplements offer health benefits and are closely regulated to ensure safety and efficacy. Unfortunately, the Dietary Supplement Health and Education Act of 1994 allows for the promotion of nutritional supplements without review by the United States Food and Drug Administration; therefore, it is important to evaluate the efficacy and safety of these supplements. There is strong scientific evidence supporting the use of plant sterols/stanols, omega-3 fatty acids, niacin, folate, vitamin B(6)/B(12), and tree nuts. There is potential evidence for the health benefits of soy protein, tea extracts, policosanol, guggulipids, coenzyme Q10, and L-arginine. There has been a lack of evidence for the health benefits of garlic and antioxidants.

Cardiovascular Diseases↗
PubMed2003

Newer pharmaceutical agents to treat lipid disorders.

The National Cholesterol Education Program Adult Treatment Panel III guidelines and the results of the Heart Protection Study have provided a stronger rationale to more aggressively treat high-risk patients to a low-density (LDL) cholesterol goal of less than 100 mL/dL. Two new therapies, ezetimibe and rosuvastatin, have recently been added to the lipid-lowering armamentarium to improve guideline adherence. Ezetimibe, a novel cholesterol absorption inhibitor, lowers LDL by 18% to 20% and can be used safely in combination with statins. Adding ezetimibe to a statin is comparable with the LDL-lowering efficacy of tripling the dose of the statin. Rosuvastatin is a highly efficacious statin providing 8% greater LDL reduction than equivalent doses of atorvastatin, and the starting dose of 10 mg/d provides nearly a 50% reduction in LDL cholesterol. There are several investigational drugs in development for the prevention and treatment of atherosclerosis. Of these investigational drugs, the most promising are the cholesterol ester transfer protein inhibitors, which have the potential to significantly raise high-density lipoprotein cholesterol and acetyl-coenzyme A: cholesterol acyltransferase inhibitors, which may directly inhibit the progression of atherosclerosis.

Anticholesteremic Agents↗
PubMed2003

Combination lipid-lowering therapy in diabetes.

Owing to the National Cholesterol Education Program Adult Treatment Panel III recommendations that patients with diabetes require a low-density lipoprotein (LDL) less than 100 mg/dL and a non-high-density lipoprotein (HDL) less than 130 mg/dL, frequently, combination lipid-lowering therapy is required. However, diabetic patients are commonly on multiple medications and have renal impairment. Therefore, the risk of myopathy with statin therapy is markedly increased. The safety of lipid-lowering therapy can be significantly improved by avoiding high-dose statins in combination with fibrates, especially gemfibrozil. To achieve non-HDL goals combining fenofibrate, or if glucose is well controlled, niacin, with a statin (not to exceed 40 mg), may significantly reduce the risk of myopathy. For diabetic patients who require additional LDL lowering, ezetimibe may provide a safe combination to a statin to achieve the LDL goal of less than 100 mg/dL.

Diabetes Mellitus↗
PubMed2003

Effect on high-density lipoprotein cholesterol of maximum dose simvastatin and atorvastatin in patients with hypercholesterolemia: results of the Comparative HDL Efficacy and Safety Study (CHESS).

BACKGROUND: Previous studies have shown that effects on high-density lipoprotein cholesterol (HDL-C) may differ among statins. METHODS: A multicenter, randomized, double-blind, parallel-dose study was conducted in 917 hypercholesterolemic patients to compare the efficacy of 80 mg/d simvastatin versus 80 mg/d atorvastatin on HDL-C and apolipoprotein (apo) A-I for 24 weeks. Efficacy was assessed as the means of weeks 6 and 12 and weeks 18 and 24. Prespecified subgroups analyzed were patients with low HDL-C levels and with the metabolic syndrome. RESULTS: Simvastatin increased HDL-C and apo A-I values significantly more than did atorvastatin for the mean of weeks 6 and 12 (8.9% vs 3.6% and 4.9% vs -0.9%, respectively) and the mean of weeks 18 and 24 (8.3% vs 4.2% and 3.7% vs -1.4%). These differences were observed across both baseline HDL-C subgroups (<40 mg/dL, > or =40 mg/dL) and in patients with the metabolic syndrome. Low-density lipoprotein cholesterol and triglyceride reductions were greater with atorvastatin. Consecutive elevations >3x the upper limit of normal in alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) occurred in significantly fewer patients treated with simvastatin than with atorvastatin (2/453 [0.4%] vs 13/464 [2.8%]), with most elevations observed in women taking atorvastatin (11/209 [5.3%] vs 1/199 [0.5%] for simvastatin). CONCLUSIONS: Simvastatin (80 mg) increased HDL-C and apo A-I significantly more than did atorvastatin (80 mg) in patients with hypercholesterolemia. This advantage was observed regardless of HDL-C level at baseline or the presence of the metabolic syndrome. Significantly fewer consecutive elevations >3x the upper limit of normal in ALT and/or AST occurred in patients receiving simvastatin.

Adult↗
PubMed2003

The safety and immunogenicity of a CETP vaccine in healthy adults.

A cholesterol ester transfer protein (CETP) vaccine (CETi-1) that induces auto-antibodies that specifically bind and inhibit activity of endogenous CETP has been demonstrated in rabbits to significantly increase HDL-C and reduce the development of atherosclerosis. In a Phase I human trial with CETi-1, one patient at the highest dose (250 mg) out of a total of 36 patients who received a single injection developed anti-CETP antibodies. In an extension study of 23 patients, 53% (8/15) who received a second injection of the active vaccine developed anti-CETP antibodies compared with 0% (0/8) in the placebo group. The vaccine was well tolerated and no significant laboratory abnormalities occurred. CETi-1 is a feasible therapy in humans to induce CETP auto-antibodies. Future research will determine if repeat inoculations will induce a sufficient anti-CETP antibody response to inhibit CETP and increase HDL levels.

Autoantibodies↗
PubMed2003

A multicenter, randomized, double-blind clinical trial comparing the low-density lipoprotein cholesterol-lowering ability of lovastatin 10, 20, and 40 mg/d with fluvastatin 20 and 40 mg/d.

BACKGROUND: The available statin drugs have similar pharmacodynamic properties but are not equal in low-density lipoprotein cholesterol (LDL-C)-lowering efficacy. OBJECTIVE: The aim of this study was to compare the effects of lovastatin and fluvastatin in lowering LDL-C. METHODS: This was a prospective, randomized, double-blind study of patients aged >20 years with primary hypercholesterolemia conducted at 44 clinical sites across the United States. After a 6-week National Cholesterol Education Program (NCEP) Step I diet lead-in period in patients taking lipid-lowering drugs at screening, patients were randomized to receive lovastatin 10, 20, or 40 mg/d or fluvastatin 20 or 40 mg/d (the doses available at the time the study was conducted) for 6 weeks. Patients not taking lipid-lowering drugs at screening and who had been following the Step I diet for at least 6 weeks proceeded to the treatment phase. All patients received instruction for a Step I diet, which they followed throughout the treatment phase. After the treatment period, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), LDL-C, and triglycerides were measured, and TC:HDL-C and LDL-C:HDL-C ratios were calculated. RESULTS: A total of 838 patients (476 men, 362 women; mean [SD] age, 59 [12] years) were included in the study. Lovastatin 20 and 40 mg/d significantly reduced mean LDL-C compared with the same dosages of fluvastatin. TC and the LDL-C:HDL-C ratio decreased more with lovastatin than with fluvastatin at a given dose level. Approximately 50% of patients treated with lovastatin 20 and 40 mg/d compared with approximately 25% treated with fluvastatin 20 and 40 mg/d reached NCEP Adult Treatment Panel II LDL-C goals. CONCLUSION: In this small study population of patients with primary hypercholesterolemia taking lipid-lowering drugs, short-term (6-week) treatment with lovastatin was more efficacious than fluvastatin in lowering cholesterol levels and reaching LDL-C treatment goals.

Cholesterol, LDL↗
PubMed2003

Lipid responses in mildly hypertriglyceridemic men and women to consumption of docosahexaenoic acid-enriched eggs.

This randomized, double-blind, controlled clinical trial assessed lipid responses in mildly hyper-triglyceridemic men and women to consumption of docosahexaenoic acid (DHA)-enriched eggs or ordinary chicken eggs. The study included 153 subjects aged 21-80 years, with serum triglyceride concentrations between 140 and 450 mg/dL, inclusive, and serum total cholesterol concentrations < 300 mg/dL. Subjects were randomly assigned to receive either DHA-enriched (147 mg DHA/egg) or ordinary eggs (20 mg DHA/egg), added to their usual diets for six weeks (10 eggs/week). Both treatments significantly lowered triglycerides and increased high-density lipoprotein (HDL) cholesterol levels from baseline; however, these changes were not significantly different between treatments. Low-density lipoprotein (LDL) cholesterol concentrations increased significantly in subjects who consumed DHA-enriched eggs (p = 0.047 vs. control). This increase was significantly higher than that observed with ordinary eggs. However, there was no significant increase in cholesterol carried by small, dense LDL particles, as determined by nuclear magnetic resonance analysis. Results of exploratory analyses suggest favorable effects of the DHA-enriched eggs over ordinary eggs on triglyceride and HDL cholesterol levels in subjects with body mass index > or = 30 kg/m2; the DHA treatment produced a larger reduction in serum triglyceride concentration vs. ordinary eggs (-12.3 vs. 2.1%; p = 0.027), and there was a greater increase for HDL cholesterol in the DHA-enriched vs. ordinary egg group (5.0 vs. 1.1%; p = 0.040).

Adult↗
PubMed2003

Food products containing free tall oil-based phytosterols and oat beta-glucan lower serum total and LDL cholesterol in hypercholesterolemic adults.

This randomized, double-blind, controlled trial evaluated the influence of low fat, low saturated fat food products that contained free tall oil-based phytosterols (TOP) and oat beta-glucan (from whole oats and bran concentrate) on serum lipid concentrations in adults with mild-to-moderate hypercholesterolemia. After a 5-wk National Cholesterol Education Program Step I diet lead-in period, 112 subjects incorporated one of two treatments into their diets for 6 wk: food products (cereal, snack bar and beverage) that provided 1.8 g TOP and 2.8 g beta-glucan/d and contained < or =3.0 g total fat and < or =1.0 g saturated fat (TOP/beta-glucan treatment) or similar control foods. The serum LDL cholesterol response from baseline to the end of study was significantly larger in the TOP/beta-glucan treated group than in the control group, in which there was no change (-3.7 vs. 0.4%; P = 0.013). Likewise, total cholesterol decreased in the TOP/beta-glucan treatment group and did not change significantly in the controls (-2.3 vs. 0.8%; P = 0.043). Serum HDL cholesterol and triglyceride responses did not differ between the groups. The results of this trial suggest that consumption of a group of low fat, TOP and beta-glucan- containing foods is a useful adjunct in the dietary management of hypercholesterolemia.

Adult↗
PubMed2003

Lipid management and the elderly.

Advancing age is an independent risk factor for the development of coronary heart disease. However, the significance of hypercholesterolemia as a cardiovascular risk factor in the elderly, has been widely debated. While no large-scale, randomized clinical trial has been conducted to evaluate cholesterol lowering solely in the elderly, evidence from older subgroups in several intervention trials supports the efficacy of lowering elevated low-density lipoprotein cholesterol for reducing cardiovascular risk in the elderly. Furthermore, although the relative risk of hyper-cholesterolemia for coronary heart disease incidence may be attenuated with advancing age, the population-wide impact of treating elevated cholesterol levels in the elderly would be large, due to the high frequency of coronary heart disease in the elderly. This article reviews key issues in the management of hyper-cholesterolemia with respect to coronary heart disease risk reduction in the elderly.

Aged↗
PubMed2003

Ezetimibe: a novel option for lowering cholesterol.

Elevated low-density lipoprotein (LDL)-cholesterol is associated with a significantly increased risk of coronary heart disease but lowering LDL-cholesterol to levels established in current National Cholesterol Education Program (NCEP) guidelines provides significant risk reduction. Nevertheless, many patients receiving lipid-lowering therapy, particularly those at highest coronary heart disease risk, do not reach LDL-cholesterol goals with their current medications. Ezetimibe (Zetia, Merck Schering-Plough) is the first of a new class of lipid-lowering drugs known as cholesterol absorption inhibitors. Ezetimibe has a favorable pharmacokinetic profile, which allows it to be administered once daily and to be given in conjunction with statins. In a series of randomized, controlled, multicenter studies, ezetimibe produced significant improvements in levels of LDL-cholesterol and other lipid parameters when used as monotherapy, with a safety profile comparable with that of placebo. Furthermore, coadministration of ezetimibe with a statin (simvastatin, atorvastatin, lovastatin, or pravastatin) was more effective than statin monotherapy in lowering LDL-cholesterol and improving other lipid parameters. Moreover, coadministration of ezetimibe with a statin allowed a greater percentage of patients to achieve treatment goals established in NCEP guidelines. The safety and side-effect profile of ezetimibe plus statin coadministration therapy was generally comparable with that of statin monotherapy. These studies establish ezetimibe as an effective lipid-lowering agent, which will likely be useful in the management of a broad range of patients with hypercholesterolemia. Ezetimibe can be used in conjunction with a statin at the beginning of therapy, or it can be added if patients do not achieve their LDL-cholesterol goal with statins alone.

Anticholesteremic Agents↗
PubMed2002

Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia.

OBJECTIVES: The purpose of this study was to assess the efficacy and safety of ezetimibe administered with simvastatin in patients with primary hypercholesterolemia. BACKGROUND: Despite the availability of statins, many patients do not achieve lipid targets. Combination therapy with lipid-lowering agents that act via a complementary pathway may allow additional patients to achieve recommended cholesterol goals. METHODS: After dietary stabilization, a 2- to 12-week washout period, and a 4-week, single-blind, placebo lead-in period, patients with baseline low-density lipoprotein cholesterol (LDL-C) > or =145 mg/dl to < or =250 mg/dl and triglycerides (TG) < or =350 mg/dl were randomized to one of the following 10 groups administered daily for 12 consecutive weeks: ezetimibe 10 mg; simvastatin 10, 20, 40, or 80 mg; ezetimibe 10 mg plus simvastatin 10, 20, 40, or 80 mg; or placebo. The primary efficacy variable was percentage reduction from baseline to end point in direct LDL-C for the pooled ezetimibe plus simvastatin groups versus pooled simvastatin groups. RESULTS: Ezetimibe plus simvastatin significantly improved LDL-C (p < 0.01), high-density lipoprotein cholesterol (HDL-C) (p = 0.03), and TG (p < 0.01) compared with simvastatin alone. Ezetimibe plus simvastatin (pooled doses) provided an incremental 13.8% LDL-C reduction, 2.4% HDL-C increase, and 7.5% TG reduction compared with pooled simvastatin alone. Coadministration of ezetimibe and simvastatin provided LDL-C reductions of 44% to 57%, TG reductions of 20% to 28%, and HDL-C increases of 8% to 11%, depending on the simvastatin dose. Ezetimibe 10 mg plus simvastatin 10 mg and simvastatin 80 mg alone each provided a 44% LDL-C reduction. The coadministration of ezetimibe with simvastatin was well tolerated, with a safety profile similar to those of simvastatin and of placebo. CONCLUSIONS: When coadministered with simvastatin, ezetimibe provided significant incremental reductions in LDL-C and TG, as well as increases in HDL-C. Coadministration of ezetimibe with simvastatin was well tolerated and comparable to statin alone.

Adult↗
PubMed2002

Combination therapy for dyslipidemia: safety and regulatory considerations.

The use of combination therapy is an effective way to manage dyslipidemia in patients with coronary artery disease (CAD). However, combination therapy is not a frequently used strategy in the treatment of CAD. Aggressive lipid-altering therapy often requires the use of combination therapy involving statins in conjunction with niacin, fibric-acid derivatives, ezetimibe, or bile acid resins. Yet, safety concerns regarding the combination of statins with other lipid-altering drugs and patient acceptance of combination therapy have influenced its application in the treatment of CAD. This article discusses several safety and regulatory considerations for the use of combination therapy for dyslipidemia.

Algorithms↗
PubMed2002

A look to the future: new treatment guidelines and a perspective on statins.

New National Cholesterol Education Program treatment guidelines incorporate a global measure of coronary heart disease (CHD) that alters risk categorization in primary prevention by identifying individuals with CHD risk equivalence on the basis of estimated absolute CHD risk. Increasing recognition of the association of on-treatment non-high-density lipoprotein (HDL) cholesterol levels with risk of CHD events is also reflected in the new guidelines by incorporation of secondary non-HDL cholesterol goals. The increased complexity of the guidelines and the likelihood of more individuals being assigned to higher risk groups with lower low-density lipoprotein (LDL) cholesterol goals is of some concern, because most patients receiving lipid-lowering therapy do not achieve current guideline LDL cholesterol goals. Increased potency of LDL cholesterol-lowering drugs would be of value in enabling more patients to achieve goals.

Cholesterol, HDL↗
PubMed2002

Strategies to improve Adult Treatment Panel III guideline adherence and patient compliance.

The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III report outlines the management of hypercholesterolemia through guidelines. These guidelines call for more aggressive diagnosis and treatment of hypercholesterolemia, which will substantially increase the number of individuals in the United States considered to be at risk for heart disease and will expand the number who will receive dietary and drug treatment. The new features of ATP III add complexity to the guidelines, which will impact adherence as well as add challenges to the management of hypercholesterolemia. Following key recommendations and incorporating essential elements of adherence can improve implementation of the NCEP ATP III guidelines. The use of global risk scoring aids, including the Palm Pilot cholesterol risk calculators, can improve guideline adherence and provide education and motivation to patients to maintain compliance.

Adult↗
PubMed2002

A multiple-dose pharmacodynamic, safety, and pharmacokinetic comparison of extended- and immediate-release formulations of lovastatin.

BACKGROUND: Because lovastatin is efficiently extracted by the liver and because its administration in divided doses is associated with increased efficacy, an extended-release (ER) formulation may have the potential for a dose-sparing advantage relative to the immediate-release (IR) formulation in the treatment of hypercholesterolemia. OBJECTIVE: This study compared the short-term pharmacodynamics, safety, and pharmacokinetics of multiple doses of lovastatin ER with those of lovastatin IR in patients with fasting low-density lipoprotein cholesterol (LDL-C) levels between 130 and 250 mg/dL and fasting triglyceride levels < 350 mg/dL. METHODS: The study had a randomized, single-blind, positive-controlled, 2-way crossover design, with a 4-week diet/placebo run-in period and two 4-week active-treatment periods. During period 1, patients received either lovastatin ER or lovastatin IR (both 40 mg OD). After 4 weeks of the initial study treatment and a 2-week washout period, patients were switched to the alternate treatment (period 2). Pharmacodynamic parameters (LDL-C, high-density lipoprotein cholesterol, total cholesterol, and triglyceride levels) were evaluated by combining data from weeks 3 and 4 of treatment. In a pharmacokinetic substudy, maximum plasma concentrations (C(max)) and area under the plasma concentration-time curve from zero to 24 hours (AUC(024)) were determined for lovastatin, lovastatin acid, and total and active inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase on days 1 and 28 of active treatment. The geometric mean ratio of AUC(0-24) (lovastatin ER/lovastatin IR) was also calculated for each of these substances. RESULTS: Of 76 patients who entered the run-in period, 26 (12 men, 14 women; mean age, 56.2 years) were randomized to receive active treatment and 24 were included in the efficacy analysis; 13 patients were included in the pharmacokinetic substudy, 12 of whom had complete pharmacokinetic data. Compared with lovastatin IR, lovastatin ER produced a 3.9% greater reduction in LDL-C (P = 0.044). Changes in other lipid parameters were not statistically significant. In the pharmacokinetic substudy, C(max) values for lovastatin, lovastatin acid, and in hibitors of HMG-CoA reductase were lower at day 28 with lovastatin ER than with lovastatin IR. The AUC(0-24) ratio for lovastatin was 1.91 (90% CI, 1.77 - 3.35), reflecting higher bioavailability of the prodrug with lovastatin ER; in contrast, the ratios for lovastatin acid and active and total inhibitors of HMG-CoA reductase were < 1. CONCLUSIONS: In this short-term study in a small number of patients, lovastatin ER 40 mg produced significantly greater LDL-C lowering than did an equal dose of lovastatin IR, with a relatively low C(max) and comparable systemic exposure to lovastatin acid and active and total inhibitors of HMG-CoA reductase. Lovastatin ER was well tolerated, with no discontinuations due to adverse events.

Adult↗
PubMed2002

Consumption of diacylglycerol oil as part of a reduced-energy diet enhances loss of body weight and fat in comparison with consumption of a triacylglycerol control oil.

BACKGROUND: Diacylglycerol is a natural component of edible oils that has metabolic characteristics that are distinct from those of triacylglycerol. OBJECTIVE: We assessed the efficacy of an oil containing mainly 1,3-diacylglycerol in reducing body weight and fat mass when incorporated into a reduced-energy diet. DESIGN: The study was a randomized, double-blind, parallel intervention trial that was conducted at an outpatient clinical research center. The subjects (n = 131) were overweight or obese men (waist circumference > or = 90 cm) and women (waist circumference > or = 87 cm). Food products (muffins, crackers, soup, cookies, and granola bars) containing diacylglycerol or triacylglycerol oil and having the same fatty acid composition were incorporated into a reduced-energy diet (2100-3350-kJ/d deficit) for 24 wk. Percentages of change in body weight, fat mass, and intraabdominal fat area were assessed. RESULTS: In an intention-to-treat analysis, body weight and fat mass decreased significantly more in the diacylglycerol group than in the triacylglycerol group (P = 0.025 and 0.037, respectively). By the end of the trial, mean body weight had decreased 3.6% and 2.5% in the diacylglycerol and triacylglycerol groups, respectively. Fat mass decreased 8.3% and 5.6% in the diacylglycerol and triacylglycerol groups, respectively. CONCLUSION: Foods containing diacylglycerol oil promoted weight loss and body fat reduction and may be useful as an adjunct to diet therapy in the management of obesity.

Abdomen↗
PubMed2002

Rosuvastatin: a highly efficacious statin for the treatment of dyslipidaemia.

Rosuvastatin is a synthetic enantiomer that is hepatoselective, relatively hydrophilic and has minimal metabolism via the cytochrome P450 3A4 system (similar to pravastatin). Rosuvastatin, like atorvastatin, has a plasma half-life of about 20 h and is a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The majority of HMG-CoA reductase inhibitory activity in plasma is associated with the parent rosuvastatin compound. In a Phase II study, rosuvastatin across a dose range of 1- 80 mg lowered low-density lipoprotein cholesterol (LDL-C) by 34 - 65%. Phase III trials have demonstrated greater reductions in LDL-C for rosuvastatin compared to atorvastatin as well as greater increases in high-density lipoprotein cholesterol (HDL-C). The drug appears to be well tolerated at all doses up to 80 mg/day. A starting dose of 10 mg will reduce LDL-C by approximately 50%, which should adequately treat most patients to within the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) goals.

Clinical Trials as Topic↗