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Management of patients with statin intolerance.
Fischer, S, Julius, U
Atherosclerosis. Supplements. 2017;:33-37
Abstract
In recent years statins have become an established option in lipid-lowering pharmacotherapy despite the fact that statin intolerance is fairly common. When muscle pains and/or an elevation of the creatine kinase appear, the dose must be lowered in patients with slight symptoms or stopped altogether if the symptoms are more severe. When the symptoms are alleviated and creatine kinase is normalized, re-exposition can be considered. If symptoms recur, treatment with another statin should be attempted - in these cases pravastatin or fluvastatin are recommended, although they are less effective in reducing LDL cholesterol. As a rule, at least 3 statins should be tested. In some patients an intake of atorvastatin or rosuvastatin twice weekly may be tolerated and effective. Alternative drugs for patients who cannot tolerate any of the statins are ezetimibe and/or bile acid sequestrants. If LDL cholesterol targets are not reached, PCSK9 inhibitors may be used. In high-risk patients with multiple cardio-vascular events and sub-optimal LDL cholesterol despite lipid-lowering drug therapy a lipoprotein apheresis should be started. In this context, we present the history of a patient, who also had high lipoprotein(a) levels, for whom lipoprotein apheresis therapy was indicated.
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Balancing Low-density Lipoprotein Cholesterol Reduction and Hepatotoxicity With Lomitapide Mesylate and Mipomersen in Patients With Homozygous Familial Hypercholesterolemia.
Won, JI, Zhang, J, Tecson, KM, McCullough, PA
Reviews in cardiovascular medicine. 2017;(1):21-28
Abstract
Homozygous familial hypercholesterolemia (HoFH) is an autosomal codominant disorder manifested by high concentrations of total cholesterol and low-density lipoprotein (LDL) cholesterol, and premature cardiovascular disease. Despite conventional lipid-lowering therapy, LDL cholesterol levels remain elevated in patients with HoFH; these patients are considered to be at high risk for cardiovascular events. In 2012-2013, two drugs with novel mechanisms of action were approved by the US Food and Drug Administration for the treatment of HoFH: lomitapide mesylate and mipomersen. Both of these treatments reduce total cholesterol, LDL cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, lipoprotein a, and triglyceride levels. This review describes the clinical tradeoffs in efficacy and hepatotoxicity of these drugs in two cases of HoFH.
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Timely diagnosis of sitosterolemia by next generation sequencing in two children with severe hypercholesterolemia.
Buonuomo, PS, Iughetti, L, Pisciotta, L, Rabacchi, C, Papadia, F, Bruzzi, P, Tummolo, A, Bartuli, A, Cortese, C, Bertolini, S, et al
Atherosclerosis. 2017;:71-77
Abstract
BACKGROUND AND AIMS Severe hypercholesterolemia associated or not with xanthomas in a child may suggest the diagnosis of homozygous autosomal dominant hypercholesterolemia (ADH), autosomal recessive hypercholesterolemia (ARH) or sitosterolemia, depending on the transmission of hypercholesterolemia in the patient's family. Sitosterolemia is a recessive disorder characterized by high plasma levels of cholesterol and plant sterols due to mutations in the ABCG5 or the ABCG8 gene, leading to a loss of function of the ATP-binding cassette (ABC) heterodimer transporter G5-G8. METHODS We aimed to perform the molecular characterization of two children with severe primary hypercholesterolemia. RESULTS Case #1 was a 2 year-old girl with high LDL-cholesterol (690 mg/dl) and tuberous and intertriginous xanthomas. Case #2 was a 7 year-old boy with elevated LDL-C (432 mg/dl) but no xanthomas. In both cases, at least one parent had elevated LDL-cholesterol levels. For the molecular diagnosis, we applied targeted next generation sequencing (NGS), which unexpectedly revealed that both patients were compound heterozygous for nonsense mutations: Case #1 in ABCG5 gene [p.(Gln251*)/p.(Arg446*)] and Case #2 in ABCG8 gene [p.(Ser107*)/p.(Trp361*)]. Both children had extremely high serum sitosterol and campesterol levels, thus confirming the diagnosis of sisterolemia. A low-fat/low-sterol diet was promptly adopted with and without the addition of ezetimibe for Case #1 and Case #2, respectively. In both patients, serum total and LDL-cholesterol decreased dramatically in two months and progressively normalized. CONCLUSIONS Targeted NGS allows the rapid diagnosis of sitosterolemia in children with severe hypercholesterolemia, even though their family history does not unequivocally suggest a recessive transmission of hypercholesterolemia. A timely diagnosis is crucial to avoid delays in treatment.
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Managing homozygous familial hypercholesterolaemia from cradle to grave.
Thompson, GR
Atherosclerosis. Supplements. 2015;:16-20
Abstract
OBJECTIVE To describe the phenotypic and genotypic features and management of clinically homozygous familial hypercholesterolaemia (FH). METHODS An analysis of current knowledge based on personal experience and published evidence. RESULTS Atherosclerotic involvement of the aortic root is common in homozygous FH and can cause death before age 5. Receptor negative patients are at greatest risk, irrespective of whether they have identical mutations (homozygous) or dissimilar mutations (compound heterozygous). CONCLUSIONS Lipoprotein apheresis combined with high dose statin and ezetimibe slows but does not arrest progression of atherosclerosis. Adjunctive use of novel compounds such as lomitapide and evolocumab should facilitate achieving the latter objective by enhancing the reduction in LDL cholesterol.
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Lomitapide for the management of homozygous familial hypercholesterolemia.
deGoma, EM
Reviews in cardiovascular medicine. 2014;(2):109-18
Abstract
Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder of low-density lipoprotein cholesterol (LDL-C) metabolism resulting in extremely elevated serum levels of LDL-C and premature atherosclerotic cardiovascular disease. Treatment typically involves multiple pharmacologic agents, as well as mechanical filtration using weekly or biweekly LDL apheresis. Despite combination lipid-lowering therapy, LDL-C levels and cardiovascular morbidity and mortality remain unacceptably high in HoFH patients. The European Commission and the US Food and Drug Administration approved the use of lomitapide, a novel medication designed to address this significant unmet need. Lomitapide is an orally administered inhibitor of microsomal triglyceride transfer protein that is indicated as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available for the reduction of LDL-C, total cholesterol, apolipoprotein B, and non-high-density lipoprotein cholesterol in adult patients with HoFH. The risks of transaminase elevations, hepatic steatosis, and gastrointestinal side effects, and the potential for drug interactions, require vigilant examination of the clinical and laboratory data and patient counseling prior to initiation of lomitapide, as well as regular monitoring during follow-up care. This article highlights important practical considerations for the use of lomitapide in the context of the evaluation and management of a HoFH patient case.
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The use of statins in people at risk of developing diabetes mellitus: evidence and guidance for clinical practice.
Sattar, NA, Ginsberg, H, Ray, K, Chapman, MJ, Arca, M, Averna, M, Betteridge, DJ, Bhatnagar, D, Bilianou, E, Carmena, R, et al
Atherosclerosis. Supplements. 2014;(1):1-15
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Abstract
Reducing low-density lipoprotein cholesterol (LDL-C) levels using statins is associated with significant reductions in cardiovascular (CV) events in a wide range of patient populations. Although statins are generally considered to be safe, recent studies suggest they are associated with an increased risk of developing Type 2 diabetes (T2D). This led the US Food and Drug Administration (FDA) to change their labelling requirements for statins to include a warning about the possibility of increased blood sugar and HbA1c levels and the European Medicines Agency (EMA) to issue guidance on a small increased risk of T2D with the statin class. This review examines the evidence leading to these claims and provides practical guidance for primary care physicians on the use of statins in people with or at risk of developing T2D. Overall, evidence suggests that the benefits of statins for the reduction of CV risk far outweigh the risk of developing T2D, especially in individuals with higher CV risk. To reduce the risk of developing T2D, physicians should assess all patients for T2D risk prior to starting statin therapy, educate patients about their risks, and encourage risk-reduction through lifestyle changes. Whether some statins are more diabetogenic than others requires further study. Statin-treated patients at high risk of developing T2D should regularly be monitored for changes in blood glucose or HbA1c levels, and the risk of conversion from pre-diabetes to T2D should be reduced by intensifying lifestyle changes. Should a patient develop T2D during statin treatment, physicians should continue with statin therapy and manage T2D in accordance with relevant national guidelines.
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Intervention in shift scheduling and changes in biomarkers of heart disease in hospital wards.
Bøggild, H, Jeppesen, HJ
Scandinavian journal of work, environment & health. 2001;(2):87-96
Abstract
OBJECTIVES The effect of introducing regularity, few consecutive night shifts, more weekends off, and only 2 different types of shifts (day-evening or day-night) into shift scheduling on biomarkers of heart disease was studied. METHODS Ergonomic shift criteria were introduced in a quasi-experimental controlled intervention in 4 hospital wards. Six wards participated as controls. Altogether 101 nurses and nurses' aides were followed for 6 months with measurements of cholesterol and triglycerides. The intervention led to more regular schedules and more staff having 2 shifts in 2 of the intervention wards 1 year after the intervention. The schedules among the controls became less regular and less predictable. The number of consecutive night shifts remained unchanged. RESULTS After 6 months the high-density lipoprotein (HDL) cholesterol level had increased in the intervention group, and the total cholesterol and low-density lipoprotein (LDL) cholesterol levels and the total:HDL cholesterol ratio had decreased. Regardless of the intervention, changes in regularity were associated with the triglyceride and HDL cholesterol levels and also with the total:HDL cholesterol ratio. More ergonomic changes were associated with lower LDL cholesterol levels, a lower total:HDL cholesterol ratio, and higher HDL cholesterol levels. CONCLUSIONS Increased ergonomic scheduling was possible. Lipids and lipoproteins changed as predicted, both when the changes were assessed in respect to the changes in schedules that resulted from the intervention and the changes that occurred regardless of the intervention. The study suggests that scheduling based on ergonomic criteria is a possible means for reducing the risk of heart disease among shift workers.