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Biomedical subjects

Michael H Davidson

Publications and source records attributed to Michael H Davidson.

78 records · Page 5Linked to original sources
PubMed2002

Controversy surrounding the safety of cerivastatin.

The noted myotoxicity and subsequent withdrawal of cerivastatin from the worldwide market in August 2001 has demonstrated that the safety of statins is not a class effect. The total rhabdomyolysis rate for cerivastatin was 16 - 80 times more frequent than with other statins without providing additional efficacy. Cerivastatin has a pharmacokinetic profile (high potency, bioavailability, lipophilicity and renal excretion) that is different from other statins, which may explain the high myotoxicity rate. The cerivastatin experience has also provided insights into high-risk populations (i.e., the elderly, women, those with renal impairment, co-administration of interacting drugs) that are more prone to statin-induced myopathy. Ultimately, the lessons learned from this experience may significantly improve the safety of statin use in the future.

Aged↗
PubMed2002

Management of hypercholesterolaemia in postmenopausal women.

Increased rates of coronary heart disease (CHD) occur with advancing age in both sexes, although CHD rates in women lag behind those of men by about 10 years. There is a sharp increase in CHD rate among women after approximately 50 years of age. The reasons for this are not completely understood and are undoubtedly multifactorial. Cross-sectional data from large-scale population studies suggest that around the time of the menopause, low-density lipoprotein (LDL)-cholesterol levels increase by approximately 15 to 25%. Because this increase is larger than that observed in men over the same age span and closely approximates that observed in women after oophorectomy, it is likely that reduced circulating estrogen levels associated with menopause play a role in the adverse changes in both blood lipid levels and CHD incidence. There is clear evidence that treating hypercholesterolemia reduces cardiovascular risk in women, as well as in men. In the US National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines, diet and other lifestyle changes are recommended as first-line therapy. If the treatment goals cannot be achieved through non-pharmacological measures, drug therapy should be added. Of the available lipid-lowering agents, HMG CoA reductase inhibitors (statins) are the clear choice to decrease LDL-cholesterol levels. However the favourable effects of statins on high-density lipoprotein (HDL)-cholesterol and triglyceride levels are more modest, and statins are not known to decrease lipoprotein (a) [Lp(a)] levels. Estrogen or hormone replacement therapy (ERT/HRT) and nicotinic acid improve LDL- and HDL-cholesterol levels and also decrease Lp(a) levels. However, ERT/HRT is no longer recommended as first-line therapy for decreasing CHD risk. Nicotinic acid is particularly useful for decreasing triglyceride levels (as are fibrates) and raising HDL-cholesterol levels. Bile-acid sequestrants reduce LDL-cholesterol and slightly increase HDL-cholesterol levels. Both bile acid sequestrants and ERT/HRT tend to raise triglyceride levels, therefore they should be used cautiously in women with hypertriglyceridaemia. Treatment should be individualised for each patient. It is important to evaluate the primary form of dyslipidaemia, other CHD risk factors, comorbidities, and the extent of lipid improvement needed in order to reach treatment goals. The effects of each type of therapy and potential adverse effects should also be considered.

Aged↗
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↗
PubMedDate not supplied

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. When used alone or in combination, these drugs decrease risk for the development and progression of atherosclerotic disease. There are strong clinical trial data to support of the use of lipid-lowering therapies in the settings of both primary and secondary prevention. This article (1) discusses the mechanisms of action of antilipidemic medications, (2) reviews dosing regimens and the pharmacokinetic differences among drugs of the same class, (3) assesses risk for drug interactions, and (4) reviews the clinical trial evidence used to support the use of particular antilipidemic medications in specific physiologic settings. The incidence of dyslipidemia is rising worldwide. This trend portends an ever-growing need for the aggressive and judicious use of different antilipidemic medication(s) in patients at risk for all forms of atherosclerotic vascular disease.

Clinical Trials as Topic↗
PubMedDate not supplied

Cholesterol-lowering drugs bring benefits to high-risk populations even when LDL is normal.

The Heart Protection Study (HPS) results were presented shortly after the National Cholesterol Education Program released the third report of clinical practice guidelines for the evaluation and management of elevated cholesterol in adults. Both the guidelines and the HPS results support an aggressive approach to managing high-risk individuals. The HPS showed that cardiovascular events and mortality were reduced in high-risk patients taking simvastatin regardless of baseline low-density lipoprotein (LDL) cholesterol levels. Some of these patients would not have met criteria for drug treatment according to the guidelines. The conclusion was that all high-risk patients with LDL > or = 100 mg/dL should be treated with drug therapy with the goal of reducing LDL to < 100 mg/dL.

Anticholesteremic Agents↗