International journal of clinical practice. Supplement最新文献

The primary objective in the management of a chronic disease is to maximise therapeutic effectiveness, according to the general consensus among specialists. Recent market research has confirmed that a treatment's effectiveness is the primary consideration for neurologists' choice of therapy for multiple sclerosis (MS). Of the available disease-modifying therapies, interferon (IFN) beta appears to be consistently more efficacious than glatiramer acetate. High doses of therapy, and frequent administration of IFN beta should be used to provide maximal effects. This has been supported by a recent Class I comparative trial of two commercial preparations of IFN beta-1a. Preliminary results indicated significantly greater efficacy for IFN beta-1a (Rebif, Serono) 44 microg administered subcutaneously three times weekly (t.i.w.), over IFN beta-1 (Avonex, Biogen) 30 microg administered intramuscularly once weekly IFN beta-1a, 44 microg t.i.w., provides maximal efficacy for patients with relapsing forms of MS.

Coronary heart disease (CHD) is the leading cause of death in patients with type 2 diabetes. The hyperglycaemia that characterises this disease is often accompanied by a cluster of other risk factors, such as dyslipidaemia and hypertension, and effective management of the patient with diabetes requires treatment directed at correcting all of the abnormalities that increase cardiovascular risk. Approximately 90% of patients with diabetes have type 2 disease, and dyslipidaemia in these patients is characterised by elevated plasma triglycerides and very-low-density lipoproteins (VLDL), by reduced high-density lipoprotein cholesterol (HDL-C), and by a shift in LDL distribution towards small, dense particles. All of these lipid abnormalities are important risk factors for CHD. Retrospective subgroup analysis and prospective studies have shown that lipid-lowering therapy can slow the progression of atherosclerosis and reduce the risk for cardiovascular events in patients with diabetes, and both the National Cholesterol Education Program Adult Treatment Panel III and American Diabetes Association have established aggressive treatment goals for lipid-lowering therapy in these patients. All of the major medications used to treat hyperlipidaemia in other populations (niacin, fibrates, bile acid sequestrants and statins) have been used effectively to improve the plasma lipid profile in patients with diabetes. Statins are generally accepted as first-line treatment for these patients, although fibrates also have an important role in patients with pronounced hypertriglyceridaemia. Statins significantly reduce low-density lipoprotein cholesterol (LDL-C) in a broad range of patients. These agents also have substantial effects on plasma triglycerides and, in patients with hypertriglyceridaemia, lower very-low-density lipoprotein cholesterol (VLDL-C) to approximately the same extent as LDL-C. In this regard, the new agent rosuvastatin has been shown, in recent trials, to produce greater decreases in these lipoproteins than currently marketed compounds. Aggressive use of agents that attack the lipid abnormalities characteristic of patients with type 2 diabetes has the potential to significantly reduce CHD risk in these individuals.

Evidence that lowering low-density cholesterol (LDL-C) reduces coronary events and mortality is now overwhelming and is reflected in treatment guidelines from around the world. The Joint European Guidelines recommend an LDL-C goal of <3.0 mmol/l in high-risk subjects. The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP)-III guidelines suggest an even more aggressive approach in high-risk individuals, with a recommended LDL-C goal of <2.6 mmol/l. Large numbers of high-risk patients are still not achieving the more conservative goals recommended in the Joint European Guidelines, let alone the more aggressive LDL-C target recommended in the new NCEPATP-III guidelines. The recognition in the NCEP ATP-III guidelines that a high-density lipoprotein cholesterol (HDL-C) level <1.0 mmol/l represents an important risk factor highlights the emergence of HDL-C as a key player in the genesis of coronary heart disease (CHD) and as a potential target for therapy. This may be especially important in people with insulin resistance with or without type 2 diabetes. There is evidence from the Helsinki Heart Study and the more recent Veterans Affairs HDL Intervention Trial (VA-HIT), both of which used gemfibrozil as the active agent, that the observed reduction in coronary events was correlated with the magnitude of the increase in HDL-C. The challenge for future management of high-risk individuals will be not only to reduce the level of LDL-C to below 2.6 mmol/l but also to increase HDL-C to levels above 1.0 mmol/l.

Individuals without overt coronary heart disease (CHD) may nevertheless be at significant risk for future CHD events based on lipid and other risk factors. Recognition of this fact is reflected in the inclusion of measures of global risk in current CHD prevention guidelines. Given the fact that many patients in the primary prevention setting fail to achieve target lipid levels, simplicity of treatment can be considered to be of great importance. Drug treatment that can improve achievement of low-density lipoprotein cholesterol (LDL-C) targets and produce beneficial effects on other lipid risk factors at starting doses would be of considerable utility in this setting. A new statin, rosuvastatin, has been shown to produce greater reductions in LDL-C and to permit more patients to reach target levels than currently available statins, and has also demonstrated favorable effects on other lipid variables. Rosuvastatin may thus be a prime candidate for use in clinical practice to achieve the lipid goals recommended in guidelines for primary prevention of CHD.

Familial hypercholesterolaemia (FH) is a hereditary metabolic disorder characterised by defects in the low-density lipoprotein (LDL) receptor, elevated LDL cholesterol (LDL-C) levels and an extremely high risk for premature cardiovascular disease. Heterozygous FH occurs in about one of every 500 individuals in the United States and Europe. The high prevalence of FH and associated morbidity and mortality strongly support aggressive screening and treatment. There are two major barriers to effective management of FH: 1) the failure to screen for this disease in people who may be at increased risk for it; and 2) the inability of most available therapies to enable achievement of LDL-C goals. More aggressive screening, coupled with new genetic screening techniques, and more powerful 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have the potential to overcome these limitations. Automated genetic assays are now available for detection of common LDL receptor mutations in individuals at risk for FH, and they have been used effectively to identify patients with this condition. Recent clinical trial results with the new synthetic statin rosuvastatin (Crestor; AstraZeneca, Alderley Park, Macclesfield, Cheshire, UK; licensed from Shionogi & Co, Ltd, Osaka, Japan) in patients with heterozygous FH have shown that it decreased LDL-C by 58% and increased high-density lipoprotein cholesterol (HDL-C) by 12%. Rosuvastatin was significantly superior to high-dose atorvastatin in improving these lipid parameters as well as total cholesterol, apolipoprotein (apo) B, apo A-I, and the LDL-C/HDL-C ratio. Thus, new screening tools and medical therapies have the potential to significantly improve management and reduce cardiovascular disease risk for patients with FH.