Biomedical subjects

Harold Bays

Publications and source records attributed to Harold Bays.

5 recordsLinked to original sources

PubMed2003

Effects of simvastatin, an HMG-CoA reductase inhibitor, in patients with hypertriglyceridemia.

BACKGROUND: Patients with elevated levels of serum triglycerides (TG) often have other associated lipid abnormalities (e.g., low levels of high-density lipoprotein cholesterol [HDL-C]) and are at increased risk of developing coronary heart disease. Although the therapeutic benefits of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in hypercholesterolemic patients have been well established, less is known about the effects of statins in patient populations with hypertriglyceridemia. HYPOTHESIS: The purpose of this study was to evaluate the lipoprotein-altering efficacy of simvastatin in hypertriglyceridemic patients. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. In all, 195 patients with fasting serum triglyceride levels between 300 and 900 mg/dl received once daily doses of placebo or simvastatin 20, 40, or 80 mg for 6 weeks. RESULTS: Compared with placebo, simvastatin treatment across all doses resulted in significant reductions (p < 0.05 - < 0.001) in serum levels of triglycerides (-20 to -31% decrease) and TG-rich lipoprotein particles. Significant (p < 0.001) reductions were also seen in low-density lipoprotein cholesterol (-25 to -35%) and non-HDL-C (-26 to -40%). Levels of HDL-C were increased (7-11%) in the simvastatin groups compared with placebo (p < 0.05 - < 0.001). CONCLUSION: The results of this study demonstrate the beneficial effects of simvastatin in patients with hypertriglyceridemia.

Adult↗

PubMed2003

Colesevelam HCl: a non-systemic lipid-altering drug.

Colesevelam HCl (WelChol, Sankyo Pharmaceuticals Inc.) is a bile acid sequestrant polymer, which has been shown to significantly lower low density lipoprotein cholesterol and favourably affect high-density lipoprotein cholesterol blood levels in monotherapy and in combination with statins (HMG-CoA reductase inhibitors). Although it is similar to other bile acid sequestrants in that it binds bile acids and is non-systemic, colesevelam HCl differs in that it has a unique polymer structure that allows for greater tolerability with less potential drug interactions than with resins. Currently, statins are the most commonly prescribed lipid-altering drugs. However, it is not uncommon that patients demonstrate true or perceived intolerances to statin therapy, that are often dose-related and may include elevations in liver or muscle enzyme blood levels, or myalgias or muscle weakness without muscle enzyme elevation. In rare circumstances, myopathy and even rhabdomyolysis can occur with statins. In addition, many statins also have important potential drug interactions. Finally, statin monotherapy is often not sufficient in achieving lipid treatment goals in many severely dyslipidaemic patients and the availability of colesevelam HCl provides a lipid-altering treatment addition to other lipid-altering drugs. From a clinical perspective, such combination therapy is often required to achieve treatment goals [1] in patients with more complicated or severe dyslipidaemia. Colesevelam HCl may also be an alternative in monotherapy for many patients with mild-to-moderate hypercholesterolaemia, as well as in some patients at potential risk from systemic exposure to alternative lipid-altering drugs (such as young children and fertile women).

Allylamine↗

PubMed2002

Existing and investigational combination drug therapy for high-density lipoprotein cholesterol.

For the past 3 to 4 decades, clinical outcomes trials have shown that drugs that favorably alter serum lipid levels reduce the risk of coronary artery disease (CAD) events. However, despite these successes, the reduction in serum low-density lipoprotein (LDL) cholesterol levels with monotherapy lipid-altering drugs does not "cure" CAD to the same degree that antibiotics "cure" many infections, nor do they "prevent" CAD in the same way that childhood immunizations "prevent" the onset of such conditions as measles, mumps, and rubella. Clinical outcome trials of monotherapy lipid-altering drugs have demonstrated a reduction in the relative risk of CAD in only a minority of patients. Thus, although safe and very effective in lowering serum LDL cholesterol levels, drugs that predominantly lower cholesterol do not "cure" atherosclerotic disease, nor have they been shown to "prevent" most CAD events in numerous clinical outcome trials. The reason for the suboptimal CAD outcomes benefits of monotherapy lipid-altering drugs is likely because atherosclerosis is a complex pathologic process with many important risk factors involved in the initiation and progression of atherosclerotic lesions and involved in the onset of the CAD event itself. An elevated serum LDL cholesterol level is an important CAD risk factor, but it is not the only lipid risk factor. A decreased serum high-density lipoprotein (HDL) cholesterol level is another important risk factor for CAD. Combination therapy through existing drugs (or possibly, in the future, through investigational lipid-altering drugs) may not only improve LDL cholesterol but also improve serum HDL cholesterol levels. This more global, multidimensional approach to lipid-altering drug treatment may provide the best chance to prevent CAD.

Anticholesteremic Agents↗

PubMed2002

Ezetimibe.

Ezetimibe is a cholesterol absorption inhibitor that significantly lowers low- density lipoprotein cholesterol (LDL-C), and favourably affects triglyceride and high-density lipoprotein cholesterol blood levels in monotherapy and in combination with statins. Hepatic and extrahepatic (peripheral) cholesterol synthesis are well-known sources of cholesterol found in LDL-C. However, the emergence of ezetimibe has highlighted intestinal cholesterol absorption as an additional, important source of cholesterol in LDL-C, and has better illuminated how genetic factors, dietary content, pharmaceutical agents, and nuclear receptor activation (such as liver X receptors) all influence the relative contribution of these important cholesterol sources to LDL-C. In fact, investigations into ezetimibe have sometimes challenged existing scientific dogma, has prompted reconsideration of older data, and has helped create 'new' paradigms in cholesterol metabolism. Thus, ezetimibe's efficacy, excellent tolerability, and safety has not only expanded potential treatment options for dyslipidaemic patients, but also has promoted exploration of new frontiers of lipid research towards a better understanding of cholesterol metabolism.

Animals↗

PubMed2002

Anti-obesity drug development.

Obesity accelerates morbidity and mortality and has been described by the World Health Organization (WHO) as an epidemic in many industrialised nations [101,102]. Diet, exercise and lifestyle recommendations have proven to be mostly ineffective in adequately preventing or treating the progression of this public health disease. Existing drug treatment is limited by the scarce number of safe and well-tolerated drugs with proven long-term efficacy in maintaining weight loss. Numerous anti-obesity drugs in development have promise. Yet, despite that obesity is the single most common nutritional problem in many developed nations and despite the devastating health consequences of this unchecked epidemic, investigational anti-obesity drugs face unique and significant challenges due to past and current experiences with anti-obesity drugs. It is anticipated that new anti-obesity drugs for this serious, multifaceted metabolic disease will become as safe and effective and as medically accepted as the treatment of other metabolic disorders such as hypertension, dyslipidaemia or Type 2 diabetes mellitus. This may be particularly important, given that these metabolic disorders may be largely due to or exacerbated by obesity itself.

Animals↗