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statin myopathy

Maha Saber-Ayad, Shaista Manzoor, Ahmed El-Serafy, Ibrahim Mahmoud, Salah Abusnana, Nabil Sulaiman
BACKGROUND: Statin-induced myopathy has been linked to the C allele of a single nucleotide polymorphism (SNP) (rs4149056) of SLCO1B1 gene. This effect is more significant, but not restricted to simvastatin. Many studies have included European, American, African and Southeast Asian ancestries, but few were carried out on Middle Eastern population. AIM: To detect the prevalence of SLCO1B1 rs4149056 (521T>C) in Emirati population. METHOD: We recruited 282 Emiratis through the UAE National Diabetes and Lifestyle Project...
March 10, 2018: Diabetes Research and Clinical Practice
David Hilton-Jones
Statins are the Marmite ('You either love it or hate it!') of the drug world, both in terms of therapeutic benefit and risk of side effects. Proponents think that they are potential life-savers, opponents that their main benefit is lining the pockets of pharma. Some consider side effects to be a major issue, outweighing any therapeutic benefit, others that they are rare and essentially innocuous. Statin-induced myalgia is relatively common but often mild and for most people does not limit treatment. In others, reducing the dose or changing the preparation may help...
March 1, 2018: Practical Neurology
Payam Mohassel, Andrew L Mammen
Anti-HMGCR myopathy was first recognized and characterized in patients with a history of statin exposure and immune-mediated necrotizing myopathy. After the discovery of anti-HMGCR autoantibodies, several international groups identified and characterized more patients, expanding the phenotypic spectrum of this disease to include pediatric patients and young adults without statin exposure and those with a chronic myopathy resembling limb-girdle muscular dystrophy. We provide a summary of clinical findings, pathologic features, muscle imaging, and immunogenetic risk factors of the disease...
2018: Journal of Neuromuscular Diseases
Albert Selva-O'Callaghan, Marcelo Alvarado-Cardenas, Iago Pinal-Fernández, Ernesto Trallero-Araguás, José Cesar Milisenda, María Ángeles Martínez, Ana Marín, Moisés Labrador-Horrillo, Cándido Juárez, Josep María Grau-Junyent
Musculoskeletal manifestations are well-recognized side effects of treatment with statins. New advances in this field have appeared in recent years. This review focuses on the diagnosis of these conditions and their underlying pathogenesis, in particular immune-mediated necrotizing myopathy. Areas covered: Clinical phenotypes including rhabdomyolysis, myalgia and/or mild hyperCKemia, self-limited toxin statin myopathy, and immune-mediated necrotizing myopathy are herein described. Therapeutic recommendations and a diagnostic algorithm in statin-associated myopathy are also proposed...
March 2018: Expert Review of Clinical Immunology
Ariane Barbacki, Sabrina A Fallavollita, Jason Karamchandani, Marie Hudson
No abstract text is available yet for this article.
February 20, 2018: Annals of Internal Medicine
Yaqin Wang, Yingying Tian, Peiyu Lv, Lulu Chen, Wei Luo, Xian Jing, Hui Li, Zhirong Tan, Yicheng Wang, Honghao Zhou, Dong-Sheng Ouyang
The pharmacokinetics of statins show substantial inter-subject variability. Increasing systemic exposure of statins may lead to adverse drug reactions such as myopathy. The variation in statin pharmacokinetics is partly explained by genetic factors. OATP1B1, coded by SLCO1B1 transports a large number of therapeutic drugs, such as atorvastatin. Here we investigated the effect of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and its metabolites. Two pharmacokinetic studies were conducted in Chinese Han volunteers and 132 volunteers were enrolled in our study as 72 in trial 1 and 60 in trial 2...
June 1, 2017: Die Pharmazie
Kushan Karunaratne, Dimitri Amiras, Matthew C Pickering, Monika Hofer, Stuart Viegas
Statins lower serum cholesterol concentrations by inhibiting the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Muscle side effects are relatively common and include asymptomatic elevation of serum creatine kinase (CK), myalgia, proximal muscle weakness and rhabdomyolysis. More recently, a subset of cases of immune-mediated necrotising myopathy has been found to have antibodies against HMGCR. It is often an aggressive and debilitating myopathy and has a complex pathogenesis characterised by fibre necrosis, usually with minimal associated inflammation...
February 8, 2018: Practical Neurology
Elizabeth De Wolf, Christopher De Wolf, Alan Richardson
There is considerable interest in redeploying drugs for use in combination with other oncology therapeutics. The single-agent activity of statins in ovarian cancer has been widely reported, however the drug concentration required to cause cell death is considerably higher than that achieved in patients receiving statin treatment for hypercholesterolemia. Unfortunately, statins can cause myopathy when administered in high doses. One solution to this is to identify drugs that could be used in combination with statins to reduce the dose required and those that may potentially reduce the incidence of adverse side effects...
February 2018: Oncology Letters
Zhixiong Zhong, Heming Wu, Bin Li, Cunren Li, Zhidong Liu, Min Yang, Qifeng Zhang, Wei Zhong, Pingsen Zhao
OBJECTIVE: Statins are the most widely used lipid-lowering drugs, which have a significant effect on the inhibition of cardiovascular disease. The efficacy and side effects of statins are associated with the polymorphisms of SLCO1B1 and APOE genes. The purpose of this study was to analyze the SLCO1B1 and APOE gene polymorphisms in the Hakka population of southern China. METHODS: A total of 3249 subjects including 2019 males and 1230 females participated in this study...
February 9, 2018: Journal of Clinical Laboratory Analysis
Baraa Alghalyini, Said El Shamieh, Ali Salami, Sophie Visvikis Siest, Hana M Fakhoury, Rajaa Fakhoury
Background Statin therapy used to lower cholesterol levels results in a substantial reduction in cardiovascular complications. Previous observations in different ethnic populations showed that rs2306283A>G, p.Asn130Asp and rs4149056T>C, p.Val174Ala in solute carrier organic anion transporter 1B1 (SLCO1B1) gene encoding the organic transporter protein may be responsible for statin uptake, thus explaining the majority of statin-associated symptoms. In addition to the genetic component, vitamin D (vit D) deficiency is common in Saudi Arabia and worldwide and may cause muscle dysfunction and ache...
February 8, 2018: Drug Metabolism and Personalized Therapy
Yanli Lu, Qingqing Hu, Lin Chen, Hong Zhang, Shibo Huang, Yuqing Xiong, Chunhua Xia
1. Deoxyschizandrin and schizandrin B have diverse pharmacological effects, including hepatoprotective activity. We aim to study their hepatic uptake and their effects on the hepatic uptake of other clinical drugs mediated by OATP1B1 and OATP1B3. 2. Deoxyschizandrin exhibited a high affinity for OATP1B1 with Km of 17.61 ± 0.43 μM but a low affinity for OATP1B3. Similarly, schizandrin B also showed a strong affinity for OATP1B1 with Km of 18.45 ± 1.23 μM but a weak affinity for OATP1B3. 3. Atorvastatin and rifampicin could inhibit the uptake of deoxyschizandrin and schizandrin B mediated by OATP1B1...
February 6, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Shiro Matsubara, Kota Bokuda, Yuri Asano, Ryo Morishima, Keizo Sugaya, Kazuhito Miyamoto, Reiji Koide, Takashi Komori, Shigeaki Suzuki, Ichizo Nishino
Immune-mediated necrotizing myopathy (IMNM) associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies occurs in patients both with and without history of statin-intake. The mechanisms of muscle fiber degeneration in this condition remain unknown. We studied pathological changes in muscle biopsies from three patients lacking history of statin-intake. Ultrastructural observations showed accumulation of degenerating mitochondria, glycogen granules and autophagic vacuoles, forming large composites in three cases, along with various nonspecific changes...
January 11, 2018: Neuromuscular Disorders: NMD
Simon B Dimmitt, Hans G Stampfer, John B Warren
Statin doses around estimated effective dose 50 (ED50) can reduce myocardial infarction by over 25% and mortality by around 10%. Being a competitive enzyme inhibitor, statin efficacy plateaus at doses that are multiples above the ED50, whilst on- and off-target adverse events increase in number and severity with increasing dose. For example, myopathy has been shown to increase by up to 29-fold and liver dysfunction by up to 9-fold as statin dose is increased. Doses of up to 40-fold ED50 have been promoted, but above 5-fold ED50, for example 10 mg of atorvastatin, there is no randomised controlled clinical trial evidence that coronary mortality is lowered, or that survival is increased...
February 2, 2018: British Journal of Clinical Pharmacology
Mostafa Shahrezaee, Ahmad Oryan, Farshid Bastami, Sepanta Hosseinpour, Mohammad Hossein Shahrezaee, Amir Kamali
PURPOSE: In addition to lipid-lowering properties, statins have been suggested to affect bone turnover by increasing the osteoblastic bone formation and blocking the osteoclastogenesis. However, there are many controversial reports regarding the beneficial effect of statins on osteoporosis. In this study, we investigated the therapeutic effects of the most important lipophilic statins administered orally for 60 days to the ovariectomized (OVX) female Sprague-Dawley rats and compared the effects on different harvested trabecular and compact bones...
January 25, 2018: Endocrine
Anqi Zhu, Donglin Zeng, Pengyue Zhang, Lang Li
One important goal in pharmaco-epidemiology studies is to understand the causal relationship between drug exposures and their clinical outcomes, including adverse drug events. In order to achieve this goal, however, we need to resolve several challenges. Most of pharmaco-epidemiology data are observational and confounding is largely present due to many co-medications. The pharmaco-epidemiology study data set is often sampled from large medical record databases using a matched case-control design, and it may not be representative of the original patient population in the medical record databases...
January 1, 2018: Statistical Methods in Medical Research
Annick Gerber, Camille Buffle Genecand, Thierry Mach, David Schrumpf, Ana Rita Forte Marques, Jean Dupraz, Thomas Schmid
Many treatments are used every day in general medicine without any evidence of their efficacy. This last year, three randomised studies tried to prove the clinical utility of chondroitin/glucosamine in arthritis, cranberry in urinary infections, and acupuncture in migraine. Screening and management of prostate cancer are still controversial. Two recent studies help us advising our patients on this difficult topic. Muscle side effects from statins are well known and have been widely relayed by the press these last years, although myopathies are rare in clinical trials...
January 17, 2018: Revue Médicale Suisse
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
Elisa Venturi, Chris Lindsay, Sabine Lotteau, Zhaokang Yang, Emma Steer, Katja Witschas, Abigail D Wilson, James R Wickens, Angela J Russell, Derek Steele, Sarah Calaghan, Rebecca Sitsapesan
BACKGROUND AND PURPOSE: Statins are amongst the most widely prescribed drugs for those at risk of cardiovascular disease, lowering cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Although effective in prevention of cardiovascular disease, statin use is associated with muscle weakness, myopathies and, in rare cases, fatal rhabdomyolysis. As simvastatin, a commonly prescribed statin, can promote Ca2+ release from sarcoplasmic reticulum (SR) vesicles, we investigated if simvastatin could directly activate skeletal (RyR1) and cardiac (RyR2) ryanodine receptors...
December 26, 2017: British Journal of Pharmacology
Coralie Pelissou, Nathalie Lerolle, Céline Labeyrie, Emmanuel Durand, Florent L Besson
Necrotizing autoimmune myopathy (NAM) is a relatively newly recognized subgroup of idiopathic inflammatory myopathies. The common histopathologic features are myocyte necrosis without significant inflammation. Necrotizing autoimmune myopathy can be associated with connective tissue disorders but can also be triggered by viral infections such as human immunodeficiency virus or malignancy, be statin-induced NAM, or be idiopathic. Here, the authors present the case of a 58-year-old man who was referred to our PET unit for a suspected paraneoplastic syndrome in a context of NAM...
February 2018: Clinical Nuclear Medicine
Emily Herrett, Elizabeth Williamson, Danielle Beaumont, Danielle Prowse, Nabila Youssouf, Kieran Brack, Jane Armitage, Ben Goldacre, Thomas MacDonald, Tjeerd van Staa, Ian Roberts, Haleema Shakur-Still, Liam Smeeth
INTRODUCTION: Statins are effective at preventing cardiovascular disease, widely prescribed and their use is growing. Uncertainty persists about whether they cause symptomatic muscle adverse effects, such as pain and weakness, in the absence of statin myopathy. Discrepancies between data from observational studies, which suggest statins are associated with excess muscle symptoms, and from randomised trials, which suggest no such excess, have caused confusion. N-of-1 trials offer the opportunity to establish whether muscle symptoms during statin use are caused by statins in particular individuals...
December 1, 2017: BMJ Open
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