Effects of raloxifene and low-dose simvastatin coadministration on plasma lipids in postmenopausal women with primary hypercholesterolemia.

Abstract Raloxifene and low-dose simvastatin can each reduce low-density lipoprotein (LDL) cholesterol without affecting high-density lipoprotein (HDL) cholesterol and triglycerides. The objective of this double-blind, 12-week study is to determine whether raloxifene and simvastatin coadministration gives added benefit beyond either monotherapy in affecting fasting lipoproteins and apolipoproteins. Ninety-five postmenopausal women with moderately elevated LDL cholesterol (mean, 146 mg/dL) were randomized to placebo, raloxifene 60 mg/d, simvastatin 10 mg/d, or raloxifene 60 mg/d coadministered with simvastatin 10 mg/d.

Lipid responses to a dietary docosahexaenoic acid supplement in men and women with below average levels of high density lipoprotein cholesterol.

Objective: To assess fasting lipid responses to a docosahexaenoic acid (DHA) supplement in men and women with below-average levels of high-density lipoprotein (HDL) cholesterol.

Methods: This randomized, double-blind, controlled clinical trial included 57 subjects, 21-80 years of age, with fasting HDL cholesterol concentrations < or =44 mg/dL (men) and < or =54 mg/dL (women), but > or =35 mg/dL. Subjects were randomly assigned to receive either 1.

Simvastatin plus ezetimibe: combination therapy for the management of dyslipidaemia.

Hyperlipidaemia is a pivotal risk factor for the development of atherosclerotic disease. A large number of studies have demonstrated that the treatment of abnormalities in lipoprotein levels reduces the risk for myocardial infarction, peripheral vascular disease, carotid artery disease, stroke, and cardiovascular mortality. Despite the development of multiple drug classes to treat dyslipidaemias and the promulgation of clearly defined guidelines for the management of lipid disorders, dyslipidaemia tends to be undertreated in the majority of patients at risk for cardiovascular disease.

Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin.

There is an increasing trend among physicians to use 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in combination with other antilipidemic agents. The complementary lipid-altering effects of statins and fibric acid derivatives (fibrates) have led to an increasing use of statin/fibrate combination therapy, particularly for patients who have mixed dyslipidemia. Clinical experience indicates that there may be an increased risk of myotoxicity associated with statin/fibrate combination therapy.

Comparative effects of lipid-lowering therapies.

The pharmacologic regulation of lipid metabolism in patients with dyslipidemia is unequivocally associated with significant reductions in risk for cardiovascular morbidity and mortality. A number of therapeutic drug classes have been developed in an effort to ever more precisely and intensively modulate lipid metabolism. Statins, fibrates, ezetimibe, and niacin exert their effects via different mechanisms and afford physicians the opportunity to beneficially impact multiple pathways in patients.

Rosuvastatin safety: lessons from the FDA review and post-approval surveillance.

Rosuvastatin is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Although highly efficacious, this new statin has generated considerable controversy regarding its safety. Rosuvastatin was approved for clinical use based on the largest pre-approval database for all statins prior to commercial use.

Evidence for altered positional specificity of LCAT in vivo: studies with docosahexaenoic acid feeding in humans.

The percentage of saturated cholesteryl esters (CEs) synthesized by human LCAT is several times higher than expected from the sn-2 acyl composition of plasma phosphatidylcholine (PC), whereas the synthesis of 20:4 CE and 22:6 CE is much lower than expected. To explain these discrepancies, we proposed that LCAT transfers some saturated fatty acids from the sn-1 position of PC species that contain 20:4 or 22:6 at sn-2. The present studies provide in vivo evidence for this hypothesis.

Efficacy and safety of ezetimibe coadministered with statins: randomised, placebo-controlled, blinded experience in 2382 patients with primary hypercholesterolemia.

We assessed pooled safety and lipid-regulating efficacy data from four similarly designed trials of ezetimibe coadministered with statins in 2382 patients with primary hypercholesterolemia. Patients were randomised to one of the following double-blind treatments for 12 weeks: placebo; ezetimibe 10 mg; statin; or statin + ezetimibe. Statin doses tested were 10, 20, 40 mg/day (atorvastatin, simvastatin, pravastatin or lovastatin) or 80 mg/day (atorvastatin, simvastatin).

Treating dyslipidemia in high-risk patients: case reviews and discussion.

The inclusion of coronary heart disease (CHD) risk equivalents in the highest CHD risk category, in addition to the lowest low-density lipoprotein cholesterol (LDL-C) targets, has dramatically increased the number of persons eligible for highly effective risk reduction and lipid-lowering treatment. Two such high-risk groups are persons with diabetes and those with metabolic syndrome. These patients typically have a number of lipid and nonlipid risk factors that require aggressive intervention.

Reducing cardiovascular risk: trends in risk, risk assessment, and cholesterol management.

The rate of decrease in coronary heart disease (CHD) mortality in the United States has slowed, probably in association with the aging of the population and the increasing rates of obesity, metabolic syndrome, and diabetes. Worldwide, guidelines for reducing risk of CHD and lowering lipid levels must continue to evolve to reflect disease and risk factor trends that reflect improvements in the knowledge of individual risk factors and the effects of clustered risk factors in specific patients. According to current guidelines used in the United States, Europe, and Canada for risk assessment and risk reduction, the trend is moving away from simple measurement of cholesterol and toward a more global risk assessment.

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.

Combination therapy in the management of complex dyslipidemias.

Purpose Of Review: Patients with dyslipidemias continue to be undertreated in both the primary and secondary prevention settings. Many patients have therapeutic needs that exceed simple reductions in low-density lipoprotein levels using statins. This review discusses the need for comprehensive management of all abnormalities in a given patient's lipoprotein profile and for the use of combinations of anti-lipidemic medications, when indicated.

Effect of contrast enhancement on measurement of carotid artery intimal medial thickness.

Previous studies have used standard B-mode ultrasound to quantify the aggregate mean intimal medial thickness (IMT) of the near and far wall of the common carotid artery (CCA). Many investigators have had difficulty in accurately evaluating the near wall IMT secondary to difficulty in discerning the vessel lumen and intima. The purpose of this study is to determine the effect of contrast enhanced ultrasound on IMT measurement when compared with non-enhanced images.

Therapeutic interventions targeted at the augmentation of reverse cholesterol transport.

Purpose Of Review: Serum high-density lipoproteins (HDLs) and reverse cholesterol transport (RCT) are important therapeutic targets in the management of atherosclerotic disease. This review summarizes the pathway of RCT and the currently available means by which investigators are attempting to modulate HDL levels and increase rates of RCT.

Recent Findings: Low levels of HDL are commonly encountered in patients with atherosclerotic disease.

Emerging therapeutic strategies for the management of dyslipidemia in patients with the metabolic syndrome.

The benefits of lipid-lowering therapy in significantly reducing cardiovascular events has been established in many at-risk populations. However, patients with the metabolic syndrome (MS) pose a challenge for clinical management. A high degree of residual risk exists in patients with the MS or diabetes mellitus, and this is of growing importance because of the increasing prevalence of obesity and its associated comorbidities in the world.

Stereoselective synthesis of d-desosamine and related glycals via tungsten-catalyzed alkynol cycloisomerization.

Stereoselective synthesis of d-desosamine diacetate ester (iii, R = Ac) was achieved from the glycal (ii). generated by tungsten carbonyl-catalyzed cycloisomerization of the corresponding amino-alkynol (i). A wide variety of N-substituents (R, R') are compatible with the cycloisomerization, provided that at least one R or R' is an acyl derivative.

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.

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.

Biologic therapies for dyslipidemia.

Biologic therapies involve the utilization of proteins, DNA, antibodies, or other substances derived or synthesized from living tissue for therapeutic effects. There are several biologic therapies in clinical development for the prevention and treatment of atherosclerosis. The most advanced in human trials are apolipoprotein mimetics, which include apolipoprotein A-1 Milano and phospholipid complexes.

Differential effects of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I are consistent across hypercholesterolemic patient subgroups.

Background: In addition to lowering plasma levels of low-density lipoprotein cholesterol (LDL-C), statins also raise high-density lipoprotein cholesterol (HDL-C).

Hypothesis: Recent studies have shown that treatment with simvastatin results in larger increases in HDL-C than those seen with atorvastatin. The results of three clinical studies are analyzed, comparing the effects of simvastatin and atorvastatin on HDL-C and apolipoprotein A-I (apo A-I) in the total cohort and in several subgroups of hypercholesterolemic patients.

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).

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.