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The Role of Statins in Current Guidelines.
Rached, F, Santos, RD
Current atherosclerosis reports. 2020;(9):50
Abstract
PURPOSE OF REVIEW The causal association of LDL-cholesterol (LDL-C) with atherosclerotic cardiovascular disease (ASCVD) has been demonstrated in robust experimental, epidemiological, genetic, and interventional randomized controlled trials (RCTs). The goal of this review is to show how the knowledge acquired from statin RCTs influenced and was recommended on guidelines for prevention of ASCVD during the last three decades. RECENT FINDINGS Guideline recommendations have evolved with accruing information derived mostly from statin RCTs, and as decades passed, more intensive LDL-C lowering was recommended according to a given ASCVD risk. Recent guidelines are unanimous in recommending intensive LDL-C lowering for the highest-risk individuals; however, they differ regarding risk stratification tools, use of specific LDL-C targets, management of primary prevention individuals, and thresholds to start non-statin lipid-lowering therapies. Even considering the advent of non-statin therapies like ezetimibe and PCSK9 inhibitors, due to their efficacy, safety, and low cost, guidelines state that statins persist as the main component of ASCVD preventive strategies and should be prescribed in adequate doses to attain evidence-based LDL-C lowering.
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Clinical Pharmacology of Statins: an Update.
Ferri, N, Corsini, A
Current atherosclerosis reports. 2020;(7):26
Abstract
PURPOSE OF REVIEW Statins represent the cornerstone for the treatment of hypercholesterolemia, although muscle-related side effects and dysregulation of glucose metabolism have strongly limited their adherence and compliance especially in primary prevention therapy. The purpose of the present review is to provide the most recent evidence of the efficacy and safety of statins in monotherapy or combination with new lipid-lowering drugs. RECENT FINDINGS Recent "life-long" analysis conducted on young familial hypercholesterolemia patients, elderly hypocholesterolemic subjects, and from a 20-year follow-up of randomized controlled trial (RCT) have been published confirming that the cardiovascular benefits of statin therapy, in patients for whom it is recommended by current guidelines, greatly outweigh the risks of side effects. In addition, recent therapies to be used in combination with statins have shown to increase the percentage of patients at goal for low-density lipoprotein - cholesterol (LDL-C) with a good safety profile. The cardiovascular (CV) benefits of monoclonal antibodies anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) and ezetimibe, in patients under statin therapy, have been proven by specific RCT, while we are still waiting for the results of bempedoic acid and the small-interfering RNA (si-RNA) anti-PCSK9 inclisiran. Taken together, the approval of new pharmacological agents to be used in combination with statins represents the future for a tailored therapy of cardiovascular disease patients.
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The Rationale, Indications, Safety, and Use of Statins in the Pediatric Population.
Khoury, M, McCrindle, BW
The Canadian journal of cardiology. 2020;(9):1372-1383
Abstract
Together with heart-healthy lifestyle habits, statins serve as the cornerstone of primary and secondary prevention of atherosclerotic cardiovascular disease in adults. Several conditions, most notably familial hypercholesterolemia (FH), cause early dyslipidemia and vascular disease, contributing to the development and progression of atherosclerosis from childhood and increased cardiovascular risk. In recent decades, studies increasingly have evaluated the safety and efficacy of statins in such high-risk youth. The strongest evidence for pediatric statin use is for the heterozygous FH population, whereby statin use has been shown to lower low-density lipoprotein cholesterol effectively, slow the progression of atherosclerosis and vascular dysfunction, and significantly reduce cardiovascular risk in early adulthood. Numerous meta-analyses and Cochrane reviews have demonstrated that attributed adverse effects, including liver toxicity, myositis, and rhabdomyolysis, occur no more frequently in youth receiving statins than placebos, with no impact on growth or development. However, further studies evaluating the long-term safety of pediatric statin use are required. In the current review, we summarize the pediatric experience of statin use to date, focusing on its utility for FH, Kawasaki disease, post-heart transplantation, and other at-risk populations. Current guidelines and indications for use are summarized, and the short- and medium-term safety experience is reviewed. Finally, a clinical approach to the indications, initiation, and monitoring of statins in youth is provided.
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The Role of Nutraceuticals in the Optimization of Lipid-Lowering Therapy in High-Risk Patients with Dyslipidaemia.
Penson, PE, Banach, M
Current atherosclerosis reports. 2020;(11):67
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PURPOSE OF REVIEW We aimed to summarize recent guidelines, position papers, and high-quality clinical research relating the use of nutraceuticals in the management of individuals at high risk of atherosclerotic cardiovascular disease. RECENT FINDINGS It is essential that individuals at high risk of cardiovascular disease receive guideline-directed evidence-based therapies to reduce their risk of morbidity and mortality from cardiovascular events. Compared with conventional therapeutics, nutraceuticals have undergone relatively little investigation in randomized controlled trials. Thus, recommendations for nutraceuticals in international guidelines are rare, and nutraceuticals should not be used preferentially in place of statins. Nevertheless, recent position papers from the International Lipid Expert Panel and clinical evidence from studies of triglyceride reduction by polyunsaturated fatty acid administration demonstrate that nutraceuticals do have an important role in optimizing therapy in individuals at high risk of cardiovascular disease. Roles for nutraceuticals include as follows: (1) managing residual risk associated with lipids other than low-density lipoprotein cholesterol (LDL-C); (2) managing non-lipid-mediated residual risk; (3) optimizing LDL-C treatment in statin intolerance; (4) optimizing LCL-C treatment when add-on therapies for statins are not available; (5) as adjuncts to lifestyle for individuals at high lifetime risk of atherosclerotic cardiovascular disease (ASCVD). The strength of evidence for each of these applications is variable. In addition to guideline-directed therapeutics, nutraceuticals may have roles in optimizing preventative therapy and targeting residual risk in individuals at high risk of ASCVD. Application of Good Manufacturing Practice and randomized controlled trials when producing and evaluating nutraceuticals will expand the armoury of evidence-based agents for the prevention of ASCVD.
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Statins as Anticancer Agents in the Era of Precision Medicine.
Longo, J, van Leeuwen, JE, Elbaz, M, Branchard, E, Penn, LZ
Clinical cancer research : an official journal of the American Association for Cancer Research. 2020;(22):5791-5800
Abstract
Statins are widely prescribed cholesterol-lowering drugs that inhibit HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate metabolic pathway. Multiple lines of evidence indicate that certain cancers depend on the mevalonate pathway for growth and survival, and, therefore, are vulnerable to statin therapy. However, these immediately available, well-tolerated, and inexpensive drugs have yet to be successfully repurposed and integrated into cancer patient care. In this review, we highlight recent advances and outline important considerations for advancing statins to clinical trials in oncology.
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Pros and cons for use of statins in people with coronavirus disease-19 (COVID-19).
Subir, R, Jagat J, M, Kalyan K, G
Diabetes & metabolic syndrome. 2020;(5):1225-1229
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BACKGROUND AND AIMS Morbidity and mortality from coronavirus disease 2019 (COVID-19) is higher among people with diabetes mellitus (DM), hypertension, and cardiovascular disease (CVD). Statins are used in the majority of people with DM and CVD. This mini-review discusses the current understanding of benefit-risk ratio of use of statins in COVID-19. METHODS We searched PubMed database using specific keywords related to our aims till June 12, 2020. Full text of relevant articles published in English language were retrieved and reviewed. RESULTS Statins, with their immunomodulatory, anti-inflammatory, anti-thrombotic, and anti-oxidant properties, have the potential to reduce severity of lung injury in, and mortality from, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) infections. Statin-induced upregulation of angiotensin-converting enzyme-2 (ACE2) has the potential to reduce lung injury from excess angiotensin II. By disrupting lipid rafts, statins have the potential to reduce viral entry into cells. However, benefit-risk ratio of its complex interaction with MYD88 gene expression on outcomes in COVID-19, and the putative role of low serum LDL cholesterol in increasing severity of SARS-CoV2 infection need further clarification. CONCLUSIONS People with COVID-19, who are already on statins for an underlying co-morbid condition, should continue on it unless there are specific contraindications. De-novo use of statins in people with COVID-19 with no underlying co-morbidity might be beneficial but awaits substantiation in clinical trials; till that time, de novo use of statins in COVID 19 should be limited to a clinical trial setting.
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Intra-coronary Imaging for the Evaluation of Plaque Modifications Induced by Drug Therapies for Secondary Prevention.
Kilic, ID, Fabris, E, Kedhi, E, Ghilencea, LN, Caiazzo, G, Sherif, SA, Di Mario, C
Current atherosclerosis reports. 2020;(12):76
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PURPOSE OF REVIEW Patients diagnosed with coronary artery disease are at a high risk of subsequent cardiovascular events; therefore, secondary prevention in the form of therapeutic lifestyle changes, and drug therapies is vital. This article aims to review potential application of intra-coronary imaging for the evaluation of plaque modifications, induced by medications for secondary prevention for CAD. RECENT FINDINGS Intra-coronary imaging provides detailed information on the atherosclerotic plaque which is the primary pathological substrate for the recurrent ischemic cardiovascular events. These modalities can detect features associated with high risk and allow serial in vivo imaging of lesions. Therefore, intravascular imaging tools have been used in landmark studies and played a role in improving our understanding of the disease processes. Changes in size and plaque composition over time can be evaluated by these tools and may help understanding the impact of a treatment. Moreover, surrogate imaging end points can be used when testing new drugs for secondary prevention.
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Statin-induced dermatomyositis for the practicing dermatologist: a review of the literature.
Visconti, MJ, Bashyam, AM, Jorizzo, JL
International journal of dermatology. 2020;(3):383-387
Abstract
Statins cause a spectrum of muscle-related adverse events, including autoimmune myopathies such as dermatomyositis (DM). This review aims to describe the events of statin-induced DM and amyopathic dermatomyositis (ADM) to increase awareness for practicing dermatologists about harmful interactions with the most commonly prescribed lipid-lowering medication. PubMed was searched for relevant literature related to statin-induced DM and ADM. Numerous cases of statin-induced DM have been reported in individuals with no history of DM or other autoimmune conditions. Statins also cause ADM, although this is a rare association. Because of the widespread use of statins worldwide for atherosclerotic disease prevention, it may be of benefit to practicing dermatologists and all clinicians to assess for a history of DM when prescribing statins and inquire if patients with a DM-like presentation are taking or have taken a statin medication.
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Familial hypercholesterolemia: Detect, treat, and ask about family.
Shah, NP, Ahmed, HM, Wilson Tang, WH
Cleveland Clinic journal of medicine. 2020;(2):109-120
Abstract
Familial hypercholesterolemia is an autosomal dominant disorder that affects the metabolism of low-density lipo-protein cholesterol (LDL-C) through mutations in the gene for LDL receptor (LDLR), and less commonly in those for apolipoprotein B (APOB), proprotein convertase subtili-sin-kexin type 9 (PCSK9), and others. Patients with these mutations have elevated plasma levels of LDL-C and, as a result, an increased risk of atherosclerotic cardiovascular disease beginning in childhood, leading to significant risk of illness and death.
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The impact of statins on physical activity and exercise capacity: an overview of the evidence, mechanisms, and recommendations.
Schweitzer, AM, Gingrich, MA, Hawke, TJ, Rebalka, IA
European journal of applied physiology. 2020;(6):1205-1225
Abstract
PURPOSE Statins are among the most widely prescribed medications worldwide. Considered the 'gold-standard' treatment for cardiovascular disease (CVD), statins inhibit HMG-CoA reductase to ultimately reduce serum LDL-cholesterol levels. Unfortunately, the main adverse event of statin use is the development of muscle-associated problems, referred to as SAMS (statin-associated muscle symptoms). While regular moderate physical activity also decreases CVD risk, there is apprehension that physical activity may induce and/or exacerbate SAMS. While much work has gone into identifying the epidemiology of SAMS, only recent research has focused on the extent to which these muscle symptoms are accompanied by functional declines. The purpose of this review is to provide an overview of possible mechanisms underlying SAMS and summarize current evidence regarding the relationship between statin treatment, physical activity, exercise capacity, and SAMS development. METHODS PubMed and Google Scholar databases were used to search the most relevant and up-to-date peer-reviewed research on the topic. RESULTS The mechanism(s) behind SAMS, including altered mitochondrial metabolism, reduced coenzyme Q10 levels, reduced vitamin D levels, impaired calcium homeostasis, elevated extracellular glutamate, and genetic polymorphisms, still lack consensus and remain up for debate. Our summation of the evidence leads us to suggest that the etiology of SAMS development is likely multifactorial. Our review also demonstrates that there is limited evidence for statins impairing exercise adaptations or reducing exercise capacity for the majority of the investigated populations. CONCLUSION The available evidence indicates that the benefits of engaging in physical activity while on statin medication largely outweigh the risks.