Statins and muscle pain

ABSTRACT

Introduction: Statins remain among the most frequently prescribed drugs and constitute a cornerstone in the prevention of cardiovascular disease. However, muscle symptoms are often reported from patients on statins. Muscle symptoms are frequently reported as adverse events associated with statin therapy.

Areas covered: In the present narrative review, statin-associated muscle pain is discussed. It elucidates potential mechanisms and possible targets for management.

Expert opinion: In general, the evidence in support of muscle pain caused by statins is in some cases equivocal and not particularly strong. Reported symptoms are difficult to quantify. Rarely is it possible to establish a causal link between statins and muscle pain. In randomized controlled trials, statins are well tolerated, and muscle-pain related side-effects is similar to placebo. There are also nocebo effects of statins. Exchange of statin may be beneficial although all statins have been associated with muscle pain. In some patients reduction of dose is worth trying, especially in primary prevention Although the benefits of statins outweigh potential risks in the vast majority of cases, careful clinical judgment may be necessary in certain cases to manage potential side effects on an individual basis.     

Statins and the potential for higher diabetes mellitus risk

ABSTRACT

Introduction: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used for cardiovascular disease (CVD) prevention. Long-term use of statins has been linked to the development of diabetes mellitus (DM) which increases CVD risk.

Areas covered: We discussed the reported incidence of DM in statin users, various possible mechanisms responsible for the development of DM and the clinical implications of this association on CVD risk. Relevant supporting literature was identified using MEDLINE/EMBASE search.

Expert opinion: Data from available RCTs and observational studies suggest a 10–45% higher risk of new-onset DM with statin use compared to nonusers. Several cellular, molecular, and genetic mechanisms, and lifestyle changes have been studied and discussed as potential underlying mechanisms responsible for this elevated DM risk with statin therapy. The mode of the diabetogenic action of statins is still unclear and an interplay of pancreatic and peripheral effects in the pathogenesis of DM is a possibility. Despite these observations, the CVD preventative benefit of statin treatment outweighs the CVD risk associated with of development of new DM. There is a need for further research to identify the exact mechanisms involved so as to specifically target causative factors and individualize treatment.     

Statins and telomere length: risk assessment and management for coronary heart disease

Cornoary heart disease (CHD) is identified as one of the diseases characterised by biological ageing as one of the important risk factors in several epidemiological studies. Premature biological ageing is distinct from chronological ageing and may predispose the individual to myocardial infarction, atherosclerosis and CHD in particular. The mean telomere length serves as a marker for the biological age at the cellular level, with shorter telomeres defining the increased biological age. Telomere length, therefore, correlates with the risk of CHD and atherosclerosis. Statins serve as the drugs of obvious choice based on their well established efficacy and safety profiles for the treatment of CHD and associated atherosclerosis. A present clinical study states that the treatment with a statin is associated with a reduction in the number of clinical events but only in individuals with increased risk based on their telomere length. This suggests a positive relationship of telomere length with the risk of CHD and, therefore, would help clinicians to categorise the patient populations based on their leucocyte telomere length for treatment with statins.     

Statins and risk of treated incident diabetes in a primary care population

Aims(i) To examine the incidence of new onset treated diabetes in patients treated with different types of statins and (ii) the relationship between the duration and dose of statins and the subsequent development of new onset treated diabetes.MethodsA retrospective cohort study was performed using the Irish Health Services Executive Primary Care Reimbursement Services national pharmacy claims database. Individuals who received any medicines were identified from January 2001 to January 2009 (n = 1 235 671). Patients newly treated with statins from 1 January 2002 to 31 December 2007 were identified (n = 239 628). Cases were identified as individuals newly treated with antidiabetic medication (n = 38 503). Adjusted hazards ratios (HR) with 95% confidence intervals (CI) were calculated to examine the association between statins (any vs. none) and time to new onset treated diabetes using Cox proportional hazard regression. The dose and duration response relationship between statins and new onset treated diabetes was examined using restricted spline functions to assess the linearity of the relationship.ResultsStatin use was associated with an increased risk of new onset treated diabetes (HR = 1.18, 95% CI 1.15, 1.22). Increased risk of new onset treated diabetes was found with rosuvastatin (HR = 1.41, 95% CI 1.31, 1.52), atorvastatin (HR = 1.23, 95% CI 1.19, 1.27) and simvastatin (HR = 1.15, 95% CI 1.05, 1.25). There were statistically significant overall dose and duration effects for all statins, excepting fluvastatin, which only demonstrated a duration effect.ConclusionAn increased risk of new onset treated diabetes was found in those treated with statins showing significant duration and dose effect. Further study is required to confirm this association.     

Statins and newly diagnosed diabetes

AIMS: In order to evaluate a hypothesized protective effect of the use of HMG Co-A reductase inhibitors (statins) on the development of Type 2 diabetes, we conducted a nested case-control study based on data from the UK-based General Practice Research Database (GPRD). METHODS: We identified a population of adults 30-79 years of age between 1 January 1991 and 31 March 2002, who were being treated with a statin or who were diagnosed with hyperlipidaemia but were not being treated with a lipid-lowering drug. From this population we identified all incident cases of Type 2 diabetes. We conducted a nested case-control study encompassing 588 cases and 2063 matched controls. FINDINGS: We observed an adjusted odds ratio (OR) of 1.1 [95% confidence interval (CI) 0.8, 1.4] for current statin users compared with non-exposed subjects and adjusted ORs for pravastatin use alone and simvastatin use alone compared with non-exposed of 0.7 (95% CI 0.4, 1.2) and 1.0 (95% CI 0.7, 1.3), respectively. There was little evidence for a duration effect for simvastatin in these data, though there is a slight suggestion of a long-term protective effect with pravastatin. CONCLUSION: The current study results are most consistent with the conclusion that there is little if any protective effect of statins on the development of Type 2 diabetes.     

微量白蛋白尿与糖尿病心血管病变关系探讨

微量白蛋白尿（MAU）不仅是早期糖尿病肾病（DN）的标志,而且与心血管病变密切相关。MAU与心血管病变存在共同的病理生理基础,即内皮损伤。充分认识MAU的危害并进行积极防治,对于减少和延缓糖尿病心血管并发症的发生和发展具有重要意义。本综述旨在探讨MAU与糖尿病心血管病变的关系。     

Cardiovascular risk factors and their management in 1282 adult people with type 1 diabetes

ABSTRACT

Objective: The mortality rate in people with type 1 diabetes (T1D) is over three-times that of their counterparts without diabetes. The underlying reason for this in the developed world is cardiovascular disease (CVD). Strict control of CVD risk factors, for which guidelines now exist, reduces morbidity and mortality. The objective of this study was to determine if these guidelines are being achieved.

Research design: Data were collected on 1282 adults with T1D from hospitals in the city of Birmingham, UK. Guidelines were those recommended by Joint British Societies: blood pressure (BP) 130/80?mmHg, total cholesterol (TC) 4?mmol/L, non-smoking status, HbA_1c 6.5% and body mass index (BMI) 25?kg/m².

Main outcome measures: The mean age was 46 years and duration of diabetes 21 years. Data on CVD risk factors were poorly documented, with a minimally defined dataset of TC, smoking history and HbA_1c being completely recorded in only 72% of people. CVD risk factor targets were also poorly achieved with only 0.7% of patients achieving all minimal dataset targets. HbA_1c and TC targets were those most poorly achieved.

Conclusions: This is the largest study of CVD risk factors in the UK and the only one to audit the standard of care provided against recent guidelines published by the joint societies. The results show that CVD risk factors are poorly recorded and sub-optimally managed in adults with T1D. Far more aggressive management is essential if mortality rates for T1D in the UK are to be reduced.     

秋水仙碱与他汀类潜在药物相互作用处方风险分析

目的 分析秋水仙碱与他汀类潜在药物相互作用（potential drug-drug interactions,pDDIS）处方,进行风险评估并制定预防措施。方法 检索知网、维普、万方、PubMed和Elsevier数据库关于秋水仙碱与他汀类相互作用致不良反应的个案和研究报道,进行文献分析;通过医院合理用药软件抽取2020年1月—2022年10月秋水仙碱联合他汀类药物的所有门诊处方,鉴别出潜在药物相互作用并进行严重性分级。结果 检索到该药物相互作用致不良反应个案报道22例,病例对照研究1篇,观察性队列研究2篇;不良反应以老年人居多,男性多于女性;发生时间集中在联合用药21 d内,3例患者死亡;高剂量、高龄、男性和肝/肾功能不全可能增加该pDDIS发生风险;遵义医科大学附属医院共收集到秋水仙碱联合他汀类药物处方72张,其中阿托伐他汀65张,瑞舒伐他汀6张,辛伐他汀1张,危险程度分级均为严重;1例患者联合使用秋水仙碱和阿托伐他汀4个月后出现肌病,1个月后好转;临床药师制定了7项预防措施。结论 遵义医科大学附属医院秋水仙碱与他汀类处方存在pDDIS,需积极实施预防措施并加强监测,尤其是联合用药早期的老年男性及肝肾功能不全患者。     

脂联素与2型糖尿病和心血管疾病

脂肪组织的内分泌功能的发现是近几年内分泌学科领域的突破性进展之一，研究表明，脂肪组织不仅是能量储存器官，而且是控制能量平衡的内分泌器官，在代谢状态改变及受外来刺激时脂肪组织可分泌多种具有生理活性的蛋白质，分泌的这些蛋白质共同命名为脂肪细胞因子，包括瘦素、肿瘤坏死因子（TNF）-α、纤溶酶原激活抑制剂-1、抵抗素、白细胞介素6（interleukin-6，IL-6）和脂联素等。脂联素（adiponectin）由于近年来的研究发现其在糖尿病及心血管疾病中具有积极作用而备受关注。本文就脂联素与2型糖尿病和心血管疾病的关系进行综述。     

Commonly used diabetes and cardiovascular medications and cancer recurrence and cancer-specific mortality: a review of the literature

Introduction: Cancer most commonly arises in the elderly who are often burdened with comorbidities. Medications used for treating these comorbidities may alter cancer prognosis. Understanding the impact of these medications on cancer is important in order to make effective evidence-based decisions about managing comorbidities while improving cancer outcomes.

Areas covered: The evidence on diabetes, statins, antihypertensive and anti-inflammatory medications and their association with cancer recurrence and cancer-specific mortality are reviewed. The strengths and limitations of the existing literature, the current state of the field and future directions are discussed.

Expert opinion: Metformin and aspirin were associated with a reduced risk of cancer recurrence and cancer-specific mortality. The evidence for statins and antihypertensive medications on cancer survival was inconsistent. There were few studies to suggest that any of the medication classes of interest were associated with negative effects on cancer survival. Methodological shortcomings within observational studies, such as confounding, distinguishing between use of medications pre-cancer versus post-cancer diagnosis/treatment, misclassification of exposures/outcomes, informative censoring and competing risks, must be considered. New observational studies addressing these limitations are essential. Some clinical trials are underway to further investigate the beneficial effects of these drugs and completed trials have confirmed results demonstrated in observational studies.     

在我国2型糖尿病患者中开展心血管终点事件临床研究的风险控制的探讨

2008年12月17日美国食品药品监督管理局(FDA)发布了"糖尿病领域指南:治疗2型糖尿病新药的心血管风险评价指导原则"。该指导原则针对如何证明一种新的治疗2型糖尿病的药物不会造成不可接受的心血管风险的增加提出了建议。目前全球正在2型糖尿病患者中开展多个以心血管事件为研究终点的大规模、长期临床研究,我国也将有选择的参与此类研究。此文件旨在阐述并提出在我国2型糖尿病患者中开展心血管终点事件临床研究的风险控制考虑,为今后开展此类研究提供指导性建议。     

他汀类药物对非缺血性心力衰竭并心房颤动患者的疗效

OBJECTIVE To study the effect of statin therapy in patients with non-ischemic heart failure(HF) and atrial fibrillation(AF).METHODS One hundred and eight patients with non-ischemic HF and AF were randomly divided into 2 groups.Patients in control group(n=     

Effects of active and passive smoking on the development of cardiovascular disease as assessed by a carotid intima‐media thickness examination in patients with type 2 diabetes mellitus

Carotid intima‐media thickness has been widely used as a surrogate end‐point for cardiovascular disease, myocardial infarction, and stroke. This study aimed to assess the effects of active and passive smoking exposure on the development of cardiovascular disease in patients with type 2 diabetes mellitus. Seven hundred twenty‐two patients with type 2 diabetes mellitus were recruited for the study. A standardized questionnaire on smoking status, pack‐years of smoking, and the number of years of smoking cessation was provided to the patients, and their responses were collected for analysis. The carotid intima‐media thickness, carotid plaque, and the internal diameter of the common carotid artery were determined by high‐resolution B‐mode ultrasonography. Compared to non‐smokers, passive female smokers had a higher risk of cardiovascular disease (odds ratio = 3.50, 95% confidence interval: 1.29–9.49, P = 0.009); they also had a significantly larger common carotid artery (P = 0.041) and risk of carotid plaque (odds ratio = 2.20, 95% confidence interval: 1.1980–4.0505, P = 0.01). Both active and passive male smokers had a significantly greater carotid intima‐media thickness than non‐smokers (P = 0.003 and P = 0.005, respectively). Male active smokers had a significantly higher risk of carotid plaque (odds ratio = 2.88, 95% confidence interval: 1.4788–5.6094, P = 0.001). In conclusion, cumulative active and passive smoking exposures are significant risk factors for carotid atherosclerosis in patients with type 2 diabetes mellitus. Our results highlight the importance of endorsing a smoke‐free environment for patients with type 2 diabetes mellitus.     

C反应蛋白与糖尿病及其心血管并发症的关系

糖尿病是严重危害人类健康的慢性进展性疾病之一,其心血管并发症是导致患者死亡的主要原因之一。C反应蛋白（CRP）是心血管疾病的敏感预测因子,近年研究证实,CRP对糖尿病及其心血管并发症预后的预测具有一定价值。现就CRP与糖尿病及其心血管并发症的关系作一综述。     

他汀类药物对非缺血性心力衰竭并心房颤动患者的疗效

目的探讨应用他汀类药物对非缺血性心力衰竭并心房颤动患者的作用。方法108例非缺血性心力衰竭并心房颤动患者,随机分为他汀类药物治疗组(50例)和对照组(58例),对照组给予常规治疗,治疗组在此基础上加用他汀类药物,所有受试者均查24h动态心电图、心脏超声彩色多普勒和6min步行距离,测定室性心律失常、左室射血分数和心功能分级,观察病死率。结果他汀类药物治疗组与对照组比较,治疗后两组左室射血分数、6min步行距离均有所提高,室性心律失常、心功能分级、病死率均下降,有统计学差异。结论他汀类药物治疗能改善非缺血性心力衰竭并心房颤动患者预后,疗效明显。     

Statins and myotoxicity: a therapeutic limitation

Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors represent the most successful class of drugs for the treatment of hypercholesterolaemia and dyslipidaemia implicated in the pathogenesis of coronary heart disease and atherosclerosis. However, the popular profile of statins in terms of efficacy has been maligned by its adverse events. The myotoxicity, ranging from mild myopathy to serious rhabdomyolysis, associated with HMG-CoA reductase inhibitors, during treatment of hypercholesterolaemia is of paramount importance. Rhabdomyolysis is a rare but idiosyncratic muscle wasting disorder of different etiologies. Statin-associated rhabdomyolysis causes skeletal muscle injury by self-perpetuating events leading to fatal irreversible renal damage through a series of biochemical reactions. Preferential distribution and action of statins in liver could be the key to minimise myotoxicity concerns. Hepato-specific distribution of statins is governed by various factors such as physicochemical properties, pharmacokinetic properties and selective transporter-mediated uptake in liver rather in extrahepatic cells. The interactions of statins with concomitant drugs of different classes merit attention for their safety profile. Although pharmacokinetic as well as pharmacodynamic interactions have been implicated in pathophysiology of statin-induced muscle wasting, the underlying mechanism is not clearly understood. Besides, pharmacokinetic and phramcodynamic factors, statin-associated myotoxcity may also implicate pharmacogenomic factors. The pharmacogenomics characterised by CYP polymorphism and other genetic factors is responsible for inter-individual variations to efficacy and tolerability of statins. The pathophysiological mechanisms may include statin-induced differences in cholesterol:phospholipid ratio, isoprenoid levels, small GTP binding proteins and apoptosis. However, the present understanding of pathophysiological mechanisms, does not offer a reliable approach to address the same at preclinical level. Although statin-associated myotoxicity affects compliance, quality of life of patient and discontinuation rate, yet the low incidence of myotoxicty including rhabdomyolysis and less severity of commonly occurring myopathy and myalgia do not raise doubts about the clinical efficacy and tolerability of statins. Medical management of myotoxicity seems to be pivotal for the proper compliance of patients with statin treatment. The appropriate and judicious use of drugs would substantially reduce the likelihood of developing clinically important myopathy.