Suggested clinical approach for the diagnosis and management of ‘statin intolerance’ with an emphasis on muscle‐related side‐effects

Hyperlipidaemia is a major risk factor for cardiovascular morbidity and mortality. 3‐hydroxy‐3‐methylglutaryl coenzyme‐A reductase inhibitors (‘statins’) are first‐line therapies for hyperlipidaemia. For each 1.0 mmoL/L reduction in low‐density lipoprotein (LDL)‐cholesterol, statins reduce the risk of major vascular events by 21% and all‐cause mortality by 9%. Owing to their clinical effectiveness and excellent safety profile, many Australians are prescribed statins. There has been widespread reporting of possible side‐effects, particularly muscle pains. Conversely, statin cessation relating to possible side‐effects exposes patients to increased risk of vascular events and death. Although there is clinical consensus for diagnosing rare side‐effects (e.g. myopathy or rhabdomyolysis), confirming that statins cause other less common side‐effects (e.g. memory impairment) is difficult as strong randomised trial evidence related to statins and non‐muscle‐related side‐effects is lacking. A stepwise approach to possible statin intolerance, consistent definitions and a simple flowchart may improve diagnosis and management. An increasing array of potential treatments is emerging, including intermittent statin dosing, new LDL‐lowering drugs, LDL apheresis and supplements. Optimal statin use and management of statin intolerance should improve cardiovascular care and clinical outcomes.     

纳米粒子包裹的他汀类药物在心血管疾病应用的研究进展

动脉粥样硬化是威胁人类生命健康最严重的疾病之一，占死亡原因的首位。动脉粥样硬化斑块一旦形成很难逆转。一种新型的药物转运系统是通过纳米粒实现的，它是生物可降解的无毒害作用的多聚物，能改变其包裹在内的药物在体内的药动学特征，增加药物在靶器官的分布量及持续时间，从而提高疗效，减轻不良反应。匹伐他汀纳米粒在缺血组织的血管新生及肺动脉高压防治的研究中已显示了巨大优势，表现为靶向定位、高效持久，并发现匹伐他汀纳米粒小剂量单次用药的效果是长期大剂量匹伐他汀的100倍甚至300倍。但尚无纳米粒他汀对动脉粥样硬化作用的研究。这一新剂型药物的的出现将为寻求药物逆转动脉粥样硬化斑块的新剂型靶向治疗药物提供方向及依据。     

他汀类药物在心房颤动治疗中的作用

他汀类药物可以减少心房颤动的发生率.现对其治疗心房颤动的作用及可能的作用机制作一综述.     

Statin Reduce the Platelet P-Selectin Expression in Atherosclerotic Ischemic Stroke

Recently, it has been demonstrated that 3-hydroxy-3-methylglutaryl coenzyme A (HMG Co-A) reductase inhibitor or statin can regulate the thrombogenesis beyond its lipid lowering effect. In this study, we investigated the beneficial effect of statin to reduce the platelet P-selectin expression in atherosclerotic ischemic stroke. Thirty-two (28 men, 4 women; mean age 59.8 ± 9.6 years) patients with atherosclerotic ischemic stroke were assigned to receive simvastatin 20 mg per day for 12 weeks and discontinued for another 12 weeks. Then, administration of simvastatin was discontinued for the following 12 weeks. Using whole blood flow cytometry, we evaluated the change of platelet P-selectin expression of all the patients after the 12-weeks use and the 12-weeks discontinuance of simvastatin. The platelet P-selectin expression was significant reduced after treatment of simvastatin 20 mg for 12 weeks (p < 0.001). However, the effect of statin to reduce platelet P-selectin expression disappeared after 12 weeks of cessation of statin. In addition, the P-selectin changes induced by statin were independent of the changes of the LDL cholesterol (r = –0.311, p = 0.386). This study demonstrated that the use of statin might be a helpful add-on therapy to regulate the platelet related thrombogenesis in atherosclerotic ischemic stroke.     

Simvastatin but not ezetimibe reduces sympathetic activity despite similar reductions in cholesterol levels

The relationship between the sympatholytic effects of statins and their lipid-lowering activity remains unclear. Ezetimibe lowers cholesterol, but its sympatholytic activity is unknown. The purpose of study was to compare the influence of equipotent doses of simvastatin and ezetimibe on sympathetic activity. This randomized double-blinded study was performed in 22 hypertensive patients (age, 45.6 ± 2.2 years; female/male, 2/20) with untreated hypercholesterolemia. The subjects were administered 20 mg/d of simvastatin (n = 11) or 20 mg/d of ezetimibe (n = 11) for 6 weeks. Pre- and post-treatment measurements of muscle sympathetic nerve activity (MSNA), baroreceptor control of heart rate (baroreflex sensitivity), and impedance cardiography were recorded. Simvastatin and ezetimibe produced similar reductions of total (−58.0 ± 23.4 vs. −45.2 ± 17.2 mg/dL; P = .15, respectively) and low-density lipoprotein cholesterol (−52.6 ± 20.9 vs. −37.9 ± 17.6 mg/dL; P = .09, respectively). There was a significant difference in the effect of simvastatin and ezetimibe on muscle sympathetic nerve activity (−8.5 ± 5.1 vs. −0.7 ± 3.5 bursts/min; P = .0005). Simvastatin improved baroreflex sensitivity as compared with ezetimibe (10.0 ± 14.3 vs. −2.8 ± 6.1 ms/mm Hg; P = .01). There was no difference in the effect of both treatments on blood pressure, heart rate, cardiac output, stroke volume, total peripheral resistance, high-density lipoprotein, and triglycerides. Simvastatin reduced sympathetic activity via lipid-independent mechanisms, but ezetimibe exerts no sympatholytic effects.     

Management of Cardiovascular Disease Risk Factors in Older Adults with Type 2 Diabetes Mellitus: 2002–2012 Literature Review

Type 2 diabetes mellitus (DM) is one of the most common chronic conditions in older adults and is often accompanied by comorbidities and geriatric syndromes. The management of cardiovascular disease risk factors in older adults with DM is important to clinicians. The literature was reviewed from 2002 to 2012 to provide an American Geriatrics Society expert panel with an evidence base for updating and making new recommendations for improving the care of older adults with type 2 DM. This review includes only the domains of the management of blood pressure, lipid control, glycemic control, and use of aspirin. Over the last 10 years, new randomized controlled trials (RCT) designed to study different blood pressure treatment targets did not find evidence that intensive systolic blood pressure control (<130 mmHg) resulted in lower rates of myocardial infarction and mortality than less‐intensive control. There are risks of side effects with achieving systolic blood pressure of less than 120 mmHg. Lipid‐lowering statins are effective in reducing cardiovascular events in middle‐aged and older adults, but data on niacin and fibrates is limited. Trials of statins and other lipid‐lowering agents do not evaluate the cardiovascular effects on outcomes from treating lipids to different low‐density lipoprotein cholesterol targets. No RCTs of lipid‐lowering drugs enrolled significant numbers of adults aged 80 and older with or without DM. Three major RCTs that investigated intensive glycemic control did not find reductions in primary cardiovascular endpoints, and one study reported greater mortality with glycosylated hemoglobin of less than 6%. Two recently published RCTs were designed to study the cardiovascular benefits of aspirin use by individuals with DM. Neither trial found significantly fewer primary cardiovascular endpoints with aspirin than in control groups. Overall, RCTs enrolled few adults aged 80 and older or with significant comorbidities. More research is needed for clinicians to effectively customize care to older adults with DM because of heterogeneity in health status, comorbidities, duration of disease, frailty and functional status, and differences in life expectancy.     

Effects of conventional and aggressive statin treatment on markers of endothelial function and inflammation

BACKGROUND: Atherosclerosis is considered to be a chronic inflammatory disorder. Several large-scale clinical studies demonstrate that markers of inflammation, such as high-sensitivity C-reactive protein (hsCRP), fibrinogen, and soluble CD40 ligand, are potent and independent predictors of vascular risk. HYPOTHESIS: The study was undertaken to investigate the effect of increasing the statin dose from conventional to aggressive treatment on lipids levels, inflammation, and endothelial function in patients with coronary artery disease (CAD). METHODS: We randomized 97 patients to either 20 mg simvastatin or 80 mg atorvastatin. Plasma levels of lipids, hsCRP, fibrinogen, soluble adhesion molecules, and nitric oxide-total were analyzed at baseline and after 6 months of treatment. RESULTS: Lipid values were significantly reduced in both treatment groups, but with significantly greater reduction in the aggressively treated group. Furthermore, aggressive statin treatment significantly decreased hsCRP and fibrinogen, while only small reductions were seen in the conventionally treated group, resulting in significant differences between the two treatment groups (p < 0.001). Nitric oxide-total increased significantly in both treatment groups, although the increase was more pronounced in the aggressively treated group (22.6 vs. 15.6%). CONCLUSION: Aggressive statin treatment significantly improved lipid status and reduced markers of inflammation and improved endothelial function compared with conventional treatment in patients with CAD. No interaction was observed, and high-dose treatment did not offer additional benefit compared with standard-dose treatment with respect to soluble adhesion molecules.     

Treatment with HMG-CoA reductase inhibitors (statins) attenuates the progression of aortic valve stenosis in the elderly

Aim:   Recent studies have shown that degenerative aortic stenosis (AS) relates to the process of atherosclerosis. The purpose of this study was to determine whether the use of 3-hydroxy-3-methygulutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) delays progression of AS in the elderly.
Methods:   Thirty-three elderly patients (> 65 years; mean age, 75 ± 6 years) with mild to moderate degenerative AS underwent two consecutive echocardiograms at least 6 months apart.
Results:   Thirteen patients were treated with statin and the remaining 20 were not treated with statin. The two groups were similar in age (74 ± 5 vs 75 ± 6 years) and initial peak pressure gradient (45 ± 27 vs 40 ± 31 mmHg). The annual increase in peak pressure gradient in statin group was smaller than that in the non-statin group (1.25 ± 5.3 mmHg/year vs 6.04 ± 6.12 mmHg/year, P  < 0.05). In multiple regression analysis, statin usage was an independent predictor of a smaller increase in peak gradient after adjusting for age, initial peak gradient, diabetes mellitus and hypertension.
Conclusions:   Statin-treated patients had delayed AS progression compared with those not treated with statin. In the elderly, statin treatment may delay the rate of progression of degenerative AS.     

他汀类药物在临床应用中的主要不良反应及防治策略

他汀类药物作为心脑血管疾病的一线用药已经在临床中被广泛应用。随着使用人群的不断扩大及研究的不断深入,他汀类药物在骨骼肌、肝脏和肾脏的不良反应及其引发糖尿病的风险开始备受关注。本文旨在汇总有关他汀类药物临床应用的新近研究结果和相关基础研究,总结其主要不良反应及防治策略,为临床应用该类药物提供参考。     

Relationship between statins and the risk of amyotrophic lateral sclerosis: A PRISMA-compliant meta-analysis

Objective:Previous studies on overlapping surveillance databases have suggested that statin use was associated with the development of amyotrophic lateral sclerosis (ALS)-like syndrome. However, the association between statin use and ALS incidence has not been clearly elucidated. To further explore this issue, we performed a systemic review and meta-analysis of all available clinical studies on the association between statin use and ALS incidence.Methods:A comprehensive database search on PubMed, Embase, Cochrane Library, and SCOPUS was conducted. We included studies up to January 31, 2020 that fulfilled our inclusion and exclusion criteria. Statin use between the ALS and control groups was collected for the meta-analysis.Results:Three case-control studies and 1 cohort study, that related the risk of ALS to statin use, satisfied the inclusion criteria for the meta-analysis. There was no statistically significant difference in statin use between the ALS and control groups (odds ratio, 0.75 [95% confidence interval, 0.53–1.08]).Conclusion:No definite association was found between statin use and the development of ALS. Further large-scale prospective randomized control studies are necessary to draw definite conclusions.     

Association of venous thromboembolism between hydrophilic and lipophilic statin users among diabetic subjects

This retrospective analysis aimed to compare the risk of venous thromboembolism (VTE) between patients with diabetes mellitus who received hydrophilic statin treatment to those who receive lipophilic statin. There were 6639 patients receiving hydrophilic statin therapy and 10,854 patients receiving lipophilic statin therapy in the study. The hazard ratios and 95% confidence intervals for VTE were estimated using univariate and multivariate Cox proportional hazards models when the study cohorts were compared. Among all patients, the incidence rate of VTE was 4.27 per 1000 person-years in the control cohort, 4.18 per 1000 person-years in the hydrophilic statin use cohort, and 3.91 per 1000 person-years in the lipophilic statin use cohort. After adjusting for age, sex, and comorbidities, the risk of VTE in the hydrophilic statin use cohort was 0.90 (0.72, 1.12) lower than that in the control cohort, the risk of VTE in the lipophilic statin use cohort was 0.87 (0.72, 1.05) lower than that in the control cohort, and the risk of VTE in the lipophilic statin use cohort was 0.97 (0.78, 1.21) lower than that in the hydrophilic statin use cohort. However, all were not statistically significant. Our result showed that there was no significant difference among the study cohorts regarding the outcome of VTE.     

A retrospective study on the preventive effect of statin after carotid artery stenting

This retrospective study appraised the preventive effect of statin after carotid artery stenting (CAS).Records were extracted for 100 patients with CAS surgery indicator, aged between 20 and 75 years old, and treated for statin. The cohort study included treatment group (statin and routine treatment) and control group (routine treatment), each group 50 patients. Outcomes consisted of degree of nerve defect (as measured by National Institute of Health Stroke Scale), lipid profiles (mg/dL), and CAS complications within 30 days after surgery.After treatment, there were no significant differences in National Institute of Health Stroke Scale, lipid profiles, and mortality rate between 2 groups. However, significant differences in total cholesterol (mg/dL, P = .03), low-density lipoprotein (mg/dL, P = .01), transient ischemic attack (P = .03), ischemic stroke (P = .04), and cardiac complications (P = .03) were identified within 30 days after CAS between 2 groups.The results of this study showed that prior statin treatment may be effective for the prevention of CAS complications.     

生长抑素在不同种属动物胃肠道分布的实验研究

目的旨在从生物进化角度探讨生长抑素在胃肠胰系统、包括阑尾、胆囊和脾脏在内的分布情况。方法应用放射免疫分析法系统探测生长抑素在小鼠、狗、猴和胎儿阑尾、胆囊和脾脏的分布。结果探测结果显示在不同哺乳类动物阑尾、胆囊和脾脏内有大量生长抑素分布。在小鼠、狗阑尾内生长抑素含量间有显著性差异（Ｐ＜０．０５），在狗和胎儿阑尾内生长抑素含量间无显著性差异。生长抑索在狗的阑尾和回肠、空肠、盲肠间无显著性差异。结论：小鼠、狗和胎儿阑尾有大量生长抑素分布。狗、猴胆囊亦有生长抑素分布