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Statin intolerance

Vesa M Olkkonen, Juha Sinisalo, Matti Jauhiainen
Remarkably good results have been achieved in the treatment of atherosclerotic cardiovascular diseases (CVD) by using statin, ezetimibe, antihypertensive, antithrombotic, and PCSK9 inhibitor therapies and their proper combinations. However, despite this success, the remaining CVD risk is still high. To target this residual risk and to treat patients who are statin-intolerant or have an exceptionally high CVD risk for instance due to familial hypercholesterolemia (FH), new therapies are intensively sought. One pathway of drug development is targeting the circulating triglyceride-rich lipoproteins (TRL) and their lipolytic remnants, which, according to the current view, confer a major CVD risk...
March 8, 2018: Atherosclerosis
Elisa Covolo, Claudio Bilato
Hyperlipidemia is a major risk factor for cardiovascular morbidity and mortality. Treatment strategies include both lifestyle modification and pharmacological therapy. Statins are among the most effective agents to achieve optimal LDL-cholesterol levels, but, not infrequently, patients suffer from myalgia or other side effects. The proven or perceived intolerance to statins requires, therefore, alternative lipid-lowering strategies. In recent years, nutraceuticals have become extensively accepted, and a growing number of molecules with hypothetical cholesterol-lowering activity have been proposed, sometimes with no scientific evidence and/or no methodological accuracy, based only on the belief that these agents are "natural" and do not show side effects...
February 2018: Giornale Italiano di Cardiologia
Charles J Glueck, Alan Brown, Anne C Goldberg, James M McKenney, Louis Kantaros, John Stewart, Joseph Elassal, Andrew Koren
BACKGROUND: The alirocumab expanded use program provided open-label access to alirocumab before its commercial availability to patients with severe hypercholesterolemia not controlled with maximally tolerated doses of standard-of-care lipid-lowering therapy. OBJECTIVE: To describe the safety and lipid-lowering efficacy of alirocumab in high-risk patients who were likely to be early users of proprotein convertase subtilisin/kexin type 9 inhibitors after approval...
February 7, 2018: Journal of Clinical Lipidology
Barbara S Wiggins, Jeffrey Senfield, Helina Kassahun, Armando Lira, Ransi Somaratne
PURPOSE OF REVIEW: To review the efficacy, safety, pharmacology, and pharmacokinetics of evolocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. RECENT FINDINGS: PCSK9 inhibitors are a class of lipid-lowering agents that significantly reduce low-density lipoprotein cholesterol (LDL-C) levels in patients with atherosclerotic cardiovascular disease and hyperlipidemia. Evolocumab is a monoclonal antibody that inhibits PCSK9 and has been evaluated in phase II and III studies as monotherapy, in combination with statins and other lipid-lowering therapies, in patients who are statin intolerant, and in patients with heterozygous and homozygous familial hypercholesterolemia...
March 6, 2018: Current Atherosclerosis Reports
Bianca Scolaro, Marina S Nogueira, Aline Paiva, Adriana Bertolami, Lucia P Barroso, Tomas Vaisar, Sean P Heffron, Edward A Fisher, Inar A Castro
OBJECTIVE: Statin intolerance, whether real or perceived, is a growing issue in clinical practice. Our aim was to evaluate the effects of reduced-dose statin therapy complemented with nutraceuticals. METHODS: First phase: Initially, 53 type 2 diabetic statin-treated patients received a supplementation with fish oil (1.7 g EPA + DHA/day), chocolate containing plant sterols (2.2 g/day), and green tea (two sachets/day) for 6 weeks. Second phase: "Good responders" to supplementation were identified after multivariate analysis (n = 10), and recruited for a pilot protocol of statin dose reduction...
February 20, 2018: Molecular Metabolism
Arrigo Francesco Giuseppe Cicero
The extracts of red yeast rice represent a nutraceutical with proven cholesterol lowering effect. Its efficacy is proportional to the concentration on monacolin K in the extract that could reach the amount of 10 mg per daily dose. The daily assumption of monacolin K could then reduce LDL-cholesterol plasma levels by 15-25% in 6-8 weeks. The LDL-cholesterol reduction is associated with a proportional reduction in total cholesterolemia, non-HDL cholesterolemia, plasma apolipoprotein B, high-sensitivity C-reactive protein, and matrix metalloproteinases 2 and 9...
February 2018: Recenti Progressi in Medicina
Baris Gencer, David Nanchen, Tinh-Hai Collet, Nicolas Rodondi, François Mach
PCSK9 (proprotein convertase subtilisin kexin 9) monoclonal antibodies (mAb) are new therapeutic agents to lower efficiently LDL-cholesterol levels. New data from large clinical trials suggest that the addition of PCSK9 mAb to statins can reduce the incidence of major adverse cardiovascular events in very high risk patients. Alirocumab and evolocumab are two agents available in Switzerland with specific limitations for reimbursement. PCSK9 mAb should be considered in patients with clinical atherosclerotic cardiovascular disease (ASCVD), as well as in patients with familial hypercholesterolemia without ASCVD who have substantially high LDL-cholesterol levels despite the use of statin at maximally tolerated dose with or without ezetimibe, or intolerance to appropriate doses of several statins...
February 28, 2018: Revue Médicale Suisse
Teresa N Harrison, Jin-Wen Y Hsu, Robert S Rosenson, Emily B Levitan, Paul Muntner, T Craig Cheetham, Rong Wei, Ronald D Scott, Kristi Reynolds
PURPOSE: A substantial percentage of patients report intolerance or side effects of statin treatment leading to treatment changes or discontinuation. The purpose of this study was to examine statin therapy changes and subsequent effects on low-density lipoprotein cholesterol (LDL-C) among patients with statin intolerance (SI). METHODS: We identified 45,037 adults from Kaiser Permanente Southern California with SI documented between 2006 and 2012. Changes in statin therapy in the year before and after the SI index date were examined...
February 2018: Cardiovascular Drugs and Therapy
Gregory S Pokrywka
Elevated low-density lipoprotein cholesterol (LDL-C) plays a major role in the development of atherosclerotic cardiovascular disease. Statins are the first-line treatment to lower LDL-C in patients with hypercholesterolemia; however, some high cardiovascular risk patients may have inadequate responses to statin therapy or are intolerant to statins, and may need additional and/or alternative non-statin therapies to further reduce their LDL-C levels. Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of circulating LDL-C levels, have received considerable attention as promising non-statin therapeutic options for the management of hypercholesterolemia...
February 23, 2018: Postgraduate Medicine
Soon Jun Hong, Han Saem Jeong, Jeong Cheon Ahn, Dong-Hun Cha, Kyung Heon Won, Weon Kim, Sang Kyoon Cho, Seok-Yeon Kim, Byung-Su Yoo, Ki Chul Sung, Seung-Woon Rha, Joon-Han Shin, Kyoo Rok Han, Wook Sung Chung, Min Su Hyon, Han Cheol Lee, Jang-Ho Bae, Moo-Yong Rhee, Jun Kwan, Dong Woon Jeon, Ki Dong Yoo, Hyo-Soo Kim
PURPOSE: Combination therapy with ezetimibe and statins is recommended in cases of statin intolerance or insufficiency. The objective of this study was to compare the efficacy and safety of combination therapy with ezetimibe and rosuvastatin versus those of rosuvastatin monotherapy in patients with hypercholesterolemia. METHODS: I-ROSETTE (Ildong ROSuvastatin & ezETimibe for hypercholesTElolemia) was an 8-week, double-blind, multicenter, Phase III randomized controlled trial conducted at 20 hospitals in the Republic of Korea...
February 2, 2018: Clinical Therapeutics
Krzysztof Chlebus, Barbara Cybulska, Marcin Gruchała, Anna Smaga, Katarzyna Wróbel, Bogdan Wojtyniak, Marcin Pajkowski, Piotr Jankowski, Tomasz Zdrojewski
BACKGROUND: Familial hypercholesterolaemia (FH) is the most common genetic disease leading to premature atherosclerosis. AIM: The aim of the study was to evaluate the prevalence, diagnosis, and treatment of FH in outpatient practice in Poland. METHODS: The study included a representative sample of 147 primary care physicians, cardiologists, and diabetologists caring for 2812 adult patients with hypercholesterolaemia and low-density lipoprotein cholesterol (LDL-C) level >1...
February 5, 2018: Kardiologia Polska
Thomas F Whayne
The clinical importance and benefit of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors appears well established for the high-risk cardiovascular (CV) patient. This applies especially to the statin-intolerant patient or the patient who does not attain an appropriate low-density lipoprotein cholesterol (LDL-C) target. Therefore, the barriers to appropriate clinical use of the PCSK9 inhibitors involve cost and not the documented CV benefit or LDL-C lowering. Multiple roadblocks affect many high-risk CV patients in arranging approval of a PCSK9 inhibitor...
February 2, 2018: Drugs
Elisa Waldmann, Charlotte Bamberger, Klaus G Parhofer
No abstract text is available yet for this article.
August 2017: Atherosclerosis
Natalie C Ward, Jing Pang, Jacqueline D M Ryan, Gerald F Watts
There is considerable evidence for the role of low-density lipoprotein cholesterol (LDL-C) in the development of atherosclerotic cardiovascular disease. Although statin therapy remains the most frequency prescribed medication to reduce LDL-C and lower risk of cardiovascular disease, a considerable number of patients develop muscle-related side affects. This review summarizes recent literature supporting the role of nutraceuticals as LDL-C-lowering therapy in statin-intolerant patients, with evidence from our own clinical practices...
January 2018: Clinical Cardiology
Donatella Zodda, Rosario Giammona, Silvia Schifilliti
Prevention and treatment of dyslipidemia should be considered as an integral part of individual cardiovascular prevention interventions, which should be addressed primarily to those at higher risk who benefit most. To date, statins remain the first-choice therapy, as they have been shown to reduce the risk of major vascular events by lowering low-density lipoprotein cholesterol (LDL-C). However, due to adherence to statin therapy or statin resistance, many patients do not reach LDL-C target levels. Ezetimibe, fibrates, and nicotinic acid represent the second-choice drugs to be used in combination with statins if lipid targets cannot be reached...
January 21, 2018: Pharmacy (Basel, Switzerland)
Francesco Di Pierro, Pietro Putignano, Nicola Villanova
BACKGROUND: Berberine, an alkaloid with both glucose- and cholesterol-lowering action, is also characterized by an anti-diarrheal effect. Consequently, berberine-based therapies are recommended for diabetic patients with irritable bowel syndrome (IBS) or gut discomfort caused by metformin. AIM: As the anti-glycemic and cholesterol-lowering action of berberine is improved by co-administration with P-glycoprotein inhibitors and naturally derived statins, we have analyzed the effect of the food supplement Berberol®K (hereafter referred to as BSM) containing, berberine, silymarin, and a highly standardized red yeast rice containing monacolins K and KA in the ratio 1:1 but no secondary monacolins, dehydromonacolins, or citrinin (Monakopure™-K20)...
January 16, 2018: Acta Bio-medica: Atenei Parmensis
Julie Rask Larsen, Lorena Dima, Christoph U Correll, Peter Manu
The metabolic syndrome includes a constellation of several well-established risk factors, which need to be aggressively treated in order to prevent overt type 2 diabetes and cardiovascular disease. While recent guidelines for the treatment of individual components of the metabolic syndrome focus on cardiovascular benefits as resulted from clinical trials, specific recent recommendations on the pharmacological management of metabolic syndrome are lacking. The objective of present paper was to review the therapeutic options for metabolic syndrome and its components, the available evidence related to their cardiovascular benefits, and to evaluate the extent to which they should influence the guidelines for clinical practice...
January 31, 2018: Expert Review of Clinical Pharmacology
Binbin Sun, Zeyu Zhong, Fan Wang, Jiong Xu, Feng Xu, Weimin Kong, Zhaoli Ling, Nan Shu, Ying Li, Tong Wu, Mian Zhang, Liang Zhu, Xiaodong Liu, Li Liu
Skeletal muscle accounts for approximately 75% of glucose disposal in body and statins impair glucose metabolism. We aimed to investigate the effect of atorvastatin on glucose metabolism in C2C12 cells. Glucose metabolism and expression of glucose transporter 4 (GLUT4) and hexokinase II (HXKII) were measured following incubation with atorvastatin or pravastatin. Roles of cholesterol in atorvastatin-induced glucose metabolism impairment were investigated via adding cholesterol or mevalonic acid and confirmed by cholesterol depletion with methyl-β-cyclodextrin...
January 12, 2018: Biochemical Pharmacology
Peter P Toth, Angelo Maria Patti, Rosaria Vincenza Giglio, Dragana Nikolic, Giuseppa Castellino, Manfredi Rizzo, Maciej Banach
Statin therapy is generally well tolerated and very effective in the prevention and treatment of cardiovascular disease, regardless of cholesterol levels; however, it can be associated with various adverse events (myalgia, myopathy, rhabdomyolysis, and diabetes mellitus, among others). Patients frequently discontinue statin therapy without medical advice because of perceived side effects and consequently increase their risk for cardiovascular events. In patients with statin intolerance, it may be advisable to change the dose, switch to a different statin, or try an alternate-day regimen...
January 9, 2018: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
Filip M Szymański, Anna E Płatek, Anna Ryś, Karolina Semczuk-Kaczmarek, Bartosz Krzowski, Katarzyna Wróbel, Krzysztof J Filipiak
BACKGROUND: Dyslipidemia, especially elevated low-density lipoprotein (LDL) cholesterol is one of the most important cardiovascular risk factors. Treatment of dyslipidemia and prevention of cardiovascular disease with lipid-lowering drugs is one of the key issues in reducing cardiovascular mortality. Nevertheless, underutilization of statins and lipid-lowering drugs is still a problem globally. AIM: The present study aimed to describe the utilization of lipid-lowering drugs in groups of patients with indications for statin treatment and elevated LDL cholesterol...
January 9, 2018: Kardiologia Polska
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