1,721,558 research outputs found
The use of statins in optimising reduction of cardiovascular risk : focus on fluvastatin
No full textPatients with widely differing degrees of cardiovascular risk can derive benefit from effective lipid-lowering therapy with statins, including patients with normal or low cholesterol levels. Clinical trials with fluvastatin have shown that it is effective in patients across a broad spectrum of cardiovascular risk. The lipid-lowering effects of fluvastatin are smaller than some statins, but major clinical outcome studies have consistently demonstrated morbidity and mortality benefits with reductions of low-density lipoprotein cholesterol of <30%. As treatment with statins is generally life-long and patients often receive multiple concomitant medications, optimal statin therapy should be well tolerated and serious consideration should be given to the avoidance of drug interactions. Although serious side-effects of statins are very rare, it is important that fluvastatin is less susceptible to drug interactions than other statins, because serious side-effects of statin therapy are generally associated with concomitant medications affecting statin metabolism. In addition, an extended-release formulation of fluvastatin has been developed to provide liver selectivity with a sustained exposure to the drug, thus improving its efficacy, and safety and tolerability profiles
The safety of HMG-CoA reductase inhibitors in special populations at high cardiovascular risk
No full textControlled clinical studies and clinical experience over many years have proven that virtually all patients benefit from lipid-lowering therapy with statins, even those with normal LDL cholesterol levels. Several recent large outcome trials have further demonstrated the clinical benefits and safety of statins in patients with a wide-range of high risks for cardiovascular disease. Those patients at highest absolute cardiovascular risk generally have the most to gain from statin therapy. A variety of statins are available to lower plasma lipids to guideline levels, but all differ in their pharmacokinetic properties, drug interaction profiles, and risk of myotoxicity. This has been highlighted by the withdrawal of cerivastatin from the market as a result of serious safety concerns. This review examines the safety and effectiveness of statins in special populations at high risk of cardiovascular disease-patients with coronary heart disease, dyslipidaemia, diabetes, hypertension, nephrotic disease, HIV, organ transplant patients and the elderly-with a focus on clinically relevant differences in the properties of individual statins that may influence the risk of drug interactions and side effect
Inhibition of cholesterol biosynthesis beyond HMG-CoA reductase: perspective and advantages
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Fluvastatin: effects beyond cholesterol lowering
No full textCoronary heart disease (CHD) remains a major therapeutic challenge in the Western world, and strategies aimed at cholesterol lowering form the mainstay of treatment. Fluvastatin is an established 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ("statin") for the treatment of hypercholesterolemia. Its efficacy and safety have been established in numerous clinical trials. Emerging evidence now indicates that treatment with fluvastatin slows the progression of atherosclerotic CHD and reduces the incidence of cardiovascular morbimortality in the secondary prevention setting. This effect of fluvastatin cannot be explained by cholesterol lowering alone; nonlipid-related mechanisms (so-called "pleiotropic effects") undoubtedly contribute to a certain extent, and are probably linked to modulation of the mevalonate pathway. This review discusses the experimental evidence regarding the antiatherosclerotic and antithrombotic effects of fluvastatin that may contribute to its beneficial action on disease progression and clinical events. Such effects include decreased expression of adhesion molecules in monocytes and leucocyte-endothelium adherence responses, immunomodulation, prevention of low-density lipoprotein oxidation, inhibition of cholesterol esterification and accumulation, along with effects on smooth muscle cell proliferation and migration. Pleiotropic actions aimed at plaque stabilization (eg, decreased secretion of matrix metalloproteinases by macrophages), together with effects on platelet activity, tissue factor expression, and endothelial function, may contribute to an antithrombotic effect of fluvastatin. Taken together, the results of these studies indicate that the effects of fluvastatin, at therapeutic doses, may extend beyond cholesterol lowering
Biomarkers for atherosclerosis: pathophysiological role and pharmacological modulation
No full textIn an attempt to improve global cardiovascular risk prediction, considerable effort has been made in the discovery and characterization of soluble biomarkers which can go beyond the measure of total and LDL cholesterol levels. In particular, circulating molecules related to chronic inflammation have emerged as potential biomarkers for atherosclerosis. Evidence, obtained from in-vitro and in-vivo experimental models, has also documented that the majority of biomarkers play a pathological role in atherogenesis. Epidemiological and clinical studies have shown strong and consistent relationships between markers of inflammation and risk for cardiovascular disease events. Biomarkers not only provide new important diagnostic and prognostic information, but may be useful to determine the pathological role of inflammatory circulating molecules in the development of atherosclerotic lesions. Moreover, biological markers may serve to identify new patients at risk of cardiovascular disease, to monitor the efficacy of antiatherosclerotic treatments, and to
develop new pharmacological tools for the treatment of atherosclerosis. Multiple screening of different biomarkers may therefore improve the assessment of risk, diagnosis, and prognosis for cardiovascular disease. In addition, soluble biomarkers have been shown to be modulated by hypolipidemic drugs and to be potentially useful in determining the clinical benefits of pharmacological therapies that do not alter serum lipid levels
Reversible and non-reversible cardiovascular risk in patients treated with lipid-lowering therapy: analysis of SEAS and JUPITER trials
No full textA number of clinical trials have confirmed that statin treatment and, more generally, LDL-lowering treatment, are able to reduce CHD and CVD events in a wide range of clinical conditions associated with increased cardiovascular risk. However, the most recent trials have also identified patient groups in which lipid-lowering treatment shows a more limited preventive potential due to the "non-reversibility" of part of the cardiovascular risk, which dilutes the observed treatment effect by events that are not directly a consequence of atherosclerosis. The use of lipid-lowering therapy in these patients should be driven not only by their absolute risk, as suggested by the most recent American and European guidelines, but also by their overall clinical setting and by the evidence of benefit obtained in controlled trials in comparable populations
Drug-drug interaction with statins
No full text3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors (the so-called statins: atorvastatin, fluvastatin, pravastatin, lovastatin, rosuvastatin and simvastatin) are a well-established class of drugs in the treatment of hypercholesterolemia. Statin monotherapy is generally well tolerated, with a low frequency of adverse events. The most important adverse effects associated with statins are myopathy and an asymptomatic increase in hepatic transaminases, both of which occur infrequently. Since statins are prescribed on a long-term basis, possible interactions with other drugs deserve particular attention, as many patients will typically receive pharmacological therapy for concomitant conditions during the course of statin treatment. Moreover, a combination of therapy between statins and other classes of lipid-lowering agents (e.g., ezetimibe, fibrates, resins and nicotinic acid) is recommended for some patients by current guidelines. Therefore, the potential for drug-drug interactions emerges as a relevant factor in determining the safety profile of statins. This review summarizes the pharmacokinetic properties of statins and emphasizes their clinically relevant drug interactions
Could changes in adiponectin drive the effect of statins on the risk of new-onset diabetes? The case of pitavastatin
No full textStatins represent the elective lipid-lowering strategy in hyperlipidemic and high cardiovascular-risk patients. Despite excellent safety and tolerability, reversible muscle-related and dose-dependent adverse events may decrease a patient’s compliance. Large meta-analyses, posthoc
and genetic studies showed that statins might increase the risk of new-onset diabetes (NOD), particularly in insulin-resistant, obese, old patients. Race, gender, concomitant medication, dose and treatment duration may also contribute to this effect. Based on this evidence, to
warn against the possibility of statin-induced NOD or worsening glycemic control in patients with already established diabetes, FDA and EMA changed the labels of all the available statins in the USA and Europe. Recent meta-analyses and retrospective studies demonstrated that
statins’ diabetogenicity is a dose-related class effect, but the mechanism(s) is not understood. Among statins, only pravastatin and pitavastatin do not deteriorate glycemic parameters in patients with and without type 2 diabetes mellitus. Interestingly, available data, obtained in smallscale,
retrospective or single-center clinical studies, document that pitavastatin, while ameliorating lipid profile, seems protective against NOD. Beyond differences in pharmacokinetics between pitavastatin and the other statins (higher oral bioavailability, lower hepatic uptake),
its consistent increases in plasma adiponectin documented in clinical studies may be causally connected with its effect on glucose metabolism. Adiponectin is a protein with antiatherosclerotic, anti-inflammatory and antidiabetogenic properties exerted on liver, skeletal muscle, adipose
tissue and pancreatic beta cells. Further studies are required to confirm this unique property of pitavastatin and to understand the mechanism(s) leading to this effect
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