Statin trials in progress: unanswered questions.

Five years ago, many critics questioned the value of lipid-lowering therapy. Today, the clinical benefits of statins are well documented, but the challenge remains to fully implement these benefits across the wide spectrum of the at-risk population, and continue to advance our understanding regarding the potential for the benefits of statins across an even broader range of select patient populations.

Does differing metabolism by cytochrome p450 have clinical importance?

The cytochrome P450 (CYP) is a group of enzymes that oxidatively modify drugs to a more water-soluble form for renal excretion. Nearly 50% of all clinically used medications and endogenous steroids are metabolized by the CYP enzyme 3A4, which explains why many of the important potential drug interactions involved this enzyme. Despite an excellent safety record, CYP 3A4 statins (lovastatin, simvastatin, atorvastatin) taken concomitantly with a potent CYP 3A4 inhibitor may increase the risk for adverse events (myopathy, rhabdomyolysis).

Effects of continuous estrogen and estrogen-progestin replacement regimens on cardiovascular risk markers in postmenopausal women.

Objective: To evaluate the influence of 2 continuous combined estrogen-progestin replacement products, compared with unopposed estrogen and placebo, on cardiovascular risk markers in postmenopausal women in a randomized, double-blind, placebo-controlled trial.

Methods: Two hundred seventy healthy postmenopausal women were randomly assigned to 1 of 4 treatment groups: placebo, unopposed 17-beta estradiol (1 mg), 1 mg of 17-beta estradiol with 0.25 mg of norethindrone acetate, or 1 mg of 17-beta estradiol with 0.

Colesevelam hydrochloride: a non-absorbed, polymeric cholesterol-lowering agent.

Colesevelam hydrochloride (formerly known as Cholestagel((R)) and re-named WelCholtrade mark, GelTex Pharmaceuticals, Inc. and Sankyo Parke-Davis) is a new, polymeric, high potency, water-absorbing hydrogel. It has been shown to be a safe and effective cholesterol-lowering agent with a non-systemic mechanism of action, good tolerability and minimal side effects.

Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers.

Objectives: To evaluate the safety and pharmacokinetics of 3-acetyl-7-oxo-DHEA (3beta-acetoxyandrost-5-ene-7,17-dione) given orally.

Design: A randomized, double blind, placebo-controlled, escalating dose study.

Setting: The Chicago Center for Clinical Research.

High-molecular-weight hydroxypropylmethylcellulose taken with or between meals is hypocholesterolemic in adult men.

Hydroxypropylmethylcellulose (HPMC) is a food gum that shares certain characteristics, such as high viscosity, with soluble fibers. In this trial, the safety and cholesterol-lowering efficacy of HPMC consumed with and between meals was evaluated in free-living male volunteers with mild-to-moderate hypercholesterolemia. After a 14-d baseline period, men (n = 51) with LDL cholesterol between 3.

Association between elevated plasma fibrinogen and the small, dense low-density lipoprotein phenotype among postmenopausal women.

A predominance of small, dense low-density lipoprotein (LDL) particles (subclass pattern B) has been associated with a 2- to threefold increase in coronary heart disease risk. Recently, it has been reported that LDL subclass pattern B is associated with hyperfibrinogenemia, which is also a coronary heart disease risk factor. The present study examined the relation between hyperfibrinogenemia and LDL subclass pattern in 258 postmenopausal women.

Low-density lipoprotein subclass distribution pattern and adiposity-associated dyslipidemia in postmenopausal women.

Objective: A predominance of small, dense low-density lipoprotein (LDL) particles (subclass pattern B) is associated with increased risk for coronary heart disease and is characterized by elevated triglycerides and depressed high-density lipoprotein (HDL) cholesterol concentrations. The present analysis was undertaken to assess the impact of LDL subclass distribution pattern and adiposity on serum lipids in postmenopausal women.

Methods: Anthropometric measurements and fasting lipid data were obtained from 254 postmenopausal women 70 years of age or younger, not receiving sex hormone replacement, who were participating in a clinical trial designed to assess the influence of hormone replacement regimens on coronary heart disease risk markers.

Cholesterol lowering with high-viscosity hydroxypropylmethylcellulose.

Hydroxypropylmethylcellulose (HPMC) is a food gum having several structural and functional properties in common with hypocholesterolemic soluble fibers. The safety and cholestero-lowering efficacy of HPMC, incorporated into a National Cholesterol Education Program Step I diet, was compared with placebo in patients with mild to moderate hypercholesterolemia. After an 8-week National Cholesterol Education Program Step I dietary lead-in phase, 160 patients with low-density lipoprotein (LDL) cholesterol between 130 and 200 mg/dl and triglycerides <300 mg/dl were randomized to placebo, 2.

Colesevelam hydrochloride (cholestagel): a new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects.

Objectives: To compare colesevelam hydrochloride (Cholestagel), a nonabsorbed hydrogel with bile acid-sequestering properties, with placebo for its lipid-lowering efficacy, its effects on laboratory and clinical safety parameters, and the incidence of adverse events.

Methods: Following diet and placebo lead-in periods, placebo or colesevelam was administered at 4 dosages (1.5, 2.

Effects of dietary inulin on serum lipids.

Inulin is a carbohydrate belonging to a class of compounds known as fructans. Because inulin is resistant to digestion in the upper gastrointestional tract it reaches the large intestine essentially intact, where it is fermented by indigenous bacteria. Thus, it may be classified as a soluble dietary fiber.

Comparison of the effects of lean red meat vs lean white meat on serum lipid levels among free-living persons with hypercholesterolemia: a long-term, randomized clinical trial.

Background: Patients with hypercholesterolemia are often counseled to limit or eliminate intake of red meats, despite evidence that lean red meats (LRMs) are not hypercholesterolemic in comparison with lean white meats (LWMs). The objective of this study was to evaluate the long-term effects on serum lipids of incorporating LRM (beef, veal, and pork) vs LWM (poultry and fish) into a National Cholesterol Education Program (NCEP) Step I diet in free-living individuals with hypercholesterolemia.

Methods: Subjects included 191 men and women with a serum low-density lipoprotein cholesterol level of 3.

Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial.

Context: Orlistat, a gastrointestinal lipase inhibitor that reduces dietary fat absorption by approximately 30%, may promote weight loss and reduce cardiovascular risk factors.

Objective: To test the hypothesis that orlistat combined with dietary intervention is more effective than placebo plus diet for weight loss and maintenance over 2 years.

Design: Randomized, double-blind, placebo-controlled study conducted from October 1992 to October 1995.

Efficacy and safety of an over-the-counter transdermal nicotine patch as an aid for smoking cessation.

Objective: To evaluate the efficacy and safety of a transdermal nicotine patch as an aid for smoking cessation in an over-the-counter setting.

Design: Multicenter, double-blind, randomized, placebo-controlled trial of 6-week duration with 18 weeks of follow-up.

Setting: Four shopping mall precincts.

A low-viscosity soluble-fiber fruit juice supplement fails to lower cholesterol in hypercholesterolemic men and women.

This study was designed to determine whether a soluble dietary fiber supplement containing gum arabic and pectin in apple juice would lower serum lipids in 110 hypercholesterolemic men and women. Subjects were stabilized on an American Heart Association Phase I Diet for 8 wk. Those with elevated low density lipoprotein cholesterol levels, despite dietary modification, continued to follow the diet and were randomly assigned to receive 720 mL/d of apple juice containing 0 (control), 5, 9 or 15 g of gum arabic and pectin (4:1 ratio) for 12 wk, followed by a 6-wk apple juice-only washout phase.

Long-term effects of consuming foods containing psyllium seed husk on serum lipids in subjects with hypercholesterolemia.

The effects of consuming foods containing 0 (control), 3.4, 6.8, or 10.

Age-dependence of the relationship between adiposity and serum low density lipoprotein cholesterol in men.

Objective: The primary aim of this study was to evaluate the effects of age on the relationships between commonly used measures of adiposity [abdominal circumference (AC) and body mass index (BMI)] and serum lipids in men.

Methods: AC, height, weight, and a fasting serum lipid profile were measured in 194 male volunteers, aged 18 to 81 years, who were free of diabetes mellitus and had participated in one of several studies on metabolic cardiovascular risk factors in the authors' laboratory. Least squares linear regression and two-way analysis of variance were used to assess relationships between measures of adiposity and fasting serum lipid values in two age groups: 18 to 49 (n = 53) and 50 to 81 years (n = 141).

Separate and joint effects of marine oil and simvastatin in patients with combined hyperlipidemia.

Marine oil plus simvastatin is an effective therapy for improving serum triglycerides, non-high-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in patients with combined hyperlipidemia. Concurrent administration does not attenuate the individual effects of either marine oil or simvastatin on the serum lipid profile.

Effectiveness of atorvastatin for reducing low-density lipoprotein cholesterol to National Cholesterol Education Program treatment goals.

Atorvastatin is a highly efficacious hydroxymethylglutaryl-coenzyme A reductase inhibitor that has been shown to reduce low-density lipoprotein cholesterol by 40% to 60%. Monotherapy with atorvastatin (10 to 80 mg/day) is well-tolerated, convenient, and appears to be effective for achieving National Cholesterol Education Program treatment goals in most patients, regardless of risk status.

A comparison of estrogen replacement, pravastatin, and combined treatment for the management of hypercholesterolemia in postmenopausal women.

Objectives: To evaluate and compare the lipid-altering effects of conjugated estrogens and pravastatin, alone and in combination, in postmenopausal women with hypercholesterolemia.

Methods: This was a double-blind, randomized, placebo-controlled clinical trial with 4 parallel groups. Participants (N = 76) were randomly assigned to receive conjugated estrogens, 0.

Comparison of one-year efficacy and safety of atorvastatin versus lovastatin in primary hypercholesterolemia. Atorvastatin Study Group I.

This double-blind study to evaluate long-term efficacy and safety of atorvastatin was performed in 31 community- and university-based research centers in the USA to directly compare a new 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (reductase inhibitor) to an accepted drug of this class in patients with moderate hypercholesterolemia. Participants remained on a cholesterol-lowering diet throughout the study. One thousand forty-nine patients were randomized to receive atorvastatin 10 mg, lovastatin 20 mg, or placebo.

Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled trial.

Objective: The objective of this study was to evaluate the effects of daily dietary supplementation with 1.25 g or 2.5 g of docosahexaenoic (DHA), in the absence of eicosapentaenoic acid (EPA), on serum lipids and lipoproteins in persons with combined hyperlipidemia (CHL) [serum low-density lipoprotein cholesterol (LDL-C) 130 to 220 mg/dL and triglycerides 150 to 400 mg/dL].

The efficacy and six-week tolerability of simvastatin 80 and 160 mg/day.

The hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin is the most effective of the currently approved hypolipidemic drugs and has been shown to reduce mortality and coronary morbidity in patients with coronary artery disease. For these patients the United States National Cholesterol Education Program advocates reducing low-density lipoprotein (LDL) cholesterol to <100 mg/dl. However, in some patients this cannot be achieved using monotherapy with simvastatin 40 mg/day, the current maximal recommended dose.