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2019 Taiwan Society of Lipids and Atherosclerosis expert consensus statement on statin intolerance.
Chien, SC, Chen, PS, Huang, YH, Tang, SC, Li, YH, Yeh, HI
Journal of the Formosan Medical Association = Taiwan yi zhi. 2019;(10):1385-1392
Abstract
Statin reduces low-density lipoprotein cholesterol and improves clinical outcomes in high risk patients. In general, statin is a safe and well-tolerated medication. However, varieties of adverse effects are reported in some patients and may interfere long-term drug compliance. Statin-associated muscle events and liver function change account for most of these adverse effects. Patients are regarded as statin intolerance if they need to discontinue statin therapy due to these adverse effects. To date, there is no universal standard definition of statin intolerance. But a pragmatic definition of statin intolerance is essential and helpful for clinicians in daily practice. In this article, after expert consensus meetings and literature review, criteria were recommended to identify patients with statin intolerance in Taiwan. The purpose of this statement is to help health care professionals in Taiwan to diagnose and manage individuals who develop muscular and hepatic side effects after statin therapy.
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Creatine as a Candidate to Prevent Statin Myopathy.
Balestrino, M, Adriano, E
Biomolecules. 2019;(9)
Abstract
Statins prevent cardiovascular diseases, yet their use is limited by the muscle disturbances they cause. Rarely, statin-induced myopathy is autoimmune, but more commonly it is due to direct muscle toxicity. Available evidence suggests that statin-induced creatine deficiency might be a major cause of this toxicity, and that creatine supplementation prevents it. Statins inhibit guanidinoacetate methyl transferase (GAMT), the last enzyme in the synthesis of creatine; thus, they decrease its intracellular content. Such decreased content could cause mitochondrial impairment, since creatine is the final acceptor of the phosphate group of adenosine triphosphate (ATP) at the end of mitochondrial oxidative phosphorylation. Decreased cellular synthesis of ATP would follow. Accordingly, ATP synthesis is decreased in statin-treated cells. In vitro, creatine supplementation prevents the opening of the mitochondrial permeability transition pore that is caused by statins. Clinically, creatine administration prevents statin myopathy in statin-intolerant patients. Additional research is warranted to hopefully confirm these findings. However, creatine is widely used by athletes with no adverse events, and has demonstrated to be safe even in double-blind, placebo-controlled trials of elderly individuals. Thus, it should be trialed, under medical supervision, in patients who cannot assume statin due to the occurrence of muscular symptoms.
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Current status of familial hypercholesterolemia in Chinese populations.
Tomlinson, B, Hu, M, Chow, E
Current opinion in lipidology. 2019;(2):94-100
Abstract
PURPOSE OF REVIEW Heterozygous familial hypercholesterolemia often went unrecognized in China when population cholesterol levels were low, but rapid economic development has changed the situation. This review will discuss the current position of awareness, diagnosis, and management of familial hypercholesterolemia in Chinese populations. RECENT FINDINGS The phenotype of familial hypercholesterolemia in China and other Chinese populations has become similar to that in Western countries, although it may still be somewhat less severe. The prevalence in Chinese populations is also similar to that in other countries and it has been found in up to 7% of Chinese patients with premature coronary heart disease. Most of the mutations are in the low-density lipoprotein receptor gene but the pattern of mutations differs from that in Whites. Chinese patients may be more responsive to statins than Whites but patients with familial hypercholesterolemia are often undertreated. SUMMARY Increasing population cholesterol levels have changed the phenotype of familial hypercholesterolemia in China and Chinese patients now resemble those in Western countries. International initiatives are facilitating increased awareness and identification of cases and more effective management of the condition.
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Cholesterol screening and statin use in children: a literature review.
King, K, Macken, A, Blake, O, O'Gorman, CS
Irish journal of medical science. 2019;(1):179-188
Abstract
Atherosclerosis begins in childhood. Fatty streaks, the earliest precursor of atherosclerotic lesions, have been found in the coronary arteries of children of 2 years of age. Hypercholesterolaemia is a risk factor for coronary artery disease. Hypercholesterolaemia can be either primary, when it is characteristic of the main disease, or secondary when it occurs as a result of either a disease process or drug treatment. Given the risk of vascular disease, including myocardial infarction (MI), cerebrovascular accidents (CVA, also known as strokes), peripheral vascular disease (PVD) and ruptured aortic aneurysm, which may follow atherosclerosis, it is important to prevent or slow the early development of atherosclerotic lesions. This prevention necessitates the control of key risk factors such hypercholesterolaemia, dyslipidaemia, hypertension etc. However, at what point this prevention ought to occur, and in what form, is uncertain. Using pharmacological primary prevention for hypercholesterolaemia in the paediatric population is controversial. In an adult patient, hypercholesterolaemia warrants the initiation of a statin. Statins, also known as hydroxymethylglutaryl co-enzyme A inhibitors (or HMG-CoA inhibitors) act by altering cholesterol metabolism. In the paediatric population, the clinical course of vascular disease and the effect of altering this clinical course are less certain. This article reviews the published literature on hypercholesterolaemia in children and the use of statins as a treatment for dyslipidaemia in children. The US National Cholesterol Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents 2012 guidelines (NCEP guidelines) regarding the recognition and treatment of childhood dyslipidaemia are reviewed.
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Current pharmacotherapeutic options for primary dyslipidemia in adults.
Cicero, AFG, Landolfo, M, Ventura, F, Borghi, C
Expert opinion on pharmacotherapy. 2019;(10):1277-1288
Abstract
INTRODUCTION Atherosclerotic cardiovascular disease (ASCVD) and its clinical manifestations, remain a leading cause of death and disability worldwide. One of the major risk factors of ASCVD is dyslipidemia and all the available guidelines suggest the importance of strategies for lipid control in a remarkable proportion of the general population. AREAS COVERED This review focuses on the therapeutic options available for the management of lipid disorders in adults. EXPERT OPINION A large body of evidence supports that statins are still the first-line option for the management of hypercholesterolemia in a large percentage of patients. Statins should be given at the appropriate dose and considering the differences in lipid-lowering potency across the different medications. The main current challenge in the treatment of lipid disorders is the need of improving patient adherence and persistence to lipid-lowering treatments beyond the drug choice and the target lipid component. To achieve this goal, the best strategy would be to treat the patients by using the appropriate drugs given at adequate doses to reach the treatment target. We should also avoid drug interactions, monitor possible untoward side effects and promote adherence to treatment by tailoring treatment strategies to each patient.
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Parenteral systems for statin delivery: a review.
Korani, S, Bahrami, S, Korani, M, Banach, M, Johnston, TP, Sahebkar, A
Lipids in health and disease. 2019;(1):193
Abstract
The oral route of drug administration is the most common and convenient route for dosing statin drugs, and, in fact, most medications, because of ease of drug delivery, patient compliance, and cost-effectiveness. However, the oral administration of statin drugs has disadvantages such as hepatic first-pass metabolism and degradation within the gastrointestinal tract that limit their overall bioavailability. This review introduces several diverse non-oral delivery methods for the administration of statins. These alternative delivery systems and routes of administration are varied and are capable of improving the bioavailability and therapeutic efficacy of statin drugs.
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Cardiovascular Risk Heterogeneity in Adults with Diabetes: Selective Use of Coronary Artery Calcium in Statin Use Decision-making.
Sarkar, S, Orimoloye, OA, Nass, CM, Blumenthal, RS, Martin, SS
Journal of general internal medicine. 2019;(11):2643-2647
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Abstract
Current American College of Cardiology/American Heart Association and American Diabetes Association guidelines recommend statin therapy for all patients with diabetes between the ages of 40 and 75, including those without cardiovascular disease (CVD). While diabetes is a major CVD risk factor, not all patients with diabetes have an equal risk of CVD. Thus, a more risk-based approach warrants consideration when recommending statin therapy for the primary prevention of CVD. Coronary artery calcium (CAC) is a noninvasive imaging modality that can help risk stratify patients with diabetes for future CVD events. CAC has been extensively studied in large cohorts such as the Multi-Ethnic Study of Atherosclerosis and found to outperform other novel risk stratification tools including carotid intima-media thickness. Moreover, a CAC score of 0 has been shown to be useful in downgrading the estimated risk of a CVD event in patients with diabetes and an intermediate Pooled Cohort Equation score. As clinicians weigh the recommendation for a lifelong therapy and the problem of statin nonadherence and patients weigh concerns about adverse effects of statins, the decision to initiate statin therapy in patients with diabetes is ideally a shared one between patients and providers, and CAC could facilitate this discussion.
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Prescription of Aspirin and Statins in Primary Prevention.
Hennekens, CH, Schuttenberg, N, Pfeffer, MA
Primary care. 2019;(1):13-25
Abstract
The increasing burden of cardiovascular disease worldwide, including the United States, underscores the need for the more widespread use of adjunctive drug therapies of proven net benefit in the primary prevention of cardiovascular disease. These include aspirin to reduce mortality from cardiovascular disease, statins to lower LDL-cholesterol levels, appropriate use of multiple antihypertensive drug therapies to lower blood pressure, and aggressive multifactorial management of diabetes. This article reviews randomized evidence to provide guidance to primary care providers regarding the use of adjunctive drug therapies.
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Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association.
Newman, CB, Preiss, D, Tobert, JA, Jacobson, TA, Page, RL, Goldstein, LB, Chin, C, Tannock, LR, Miller, M, Raghuveer, G, et al
Arteriosclerosis, thrombosis, and vascular biology. 2019;(2):e38-e81
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Abstract
One in 4 Americans >40 years of age takes a statin to reduce the risk of myocardial infarction, ischemic stroke, and other complications of atherosclerotic disease. The most effective statins produce a mean reduction in low-density lipoprotein cholesterol of 55% to 60% at the maximum dosage, and 6 of the 7 marketed statins are available in generic form, which makes them affordable for most patients. Primarily using data from randomized controlled trials, supplemented with observational data where necessary, this scientific statement provides a comprehensive review of statin safety and tolerability. The review covers the general patient population, as well as demographic subgroups, including the elderly, children, pregnant women, East Asians, and patients with specific conditions such as chronic disease of the kidney and liver, human immunodeficiency viral infection, and organ transplants. The risk of statin-induced serious muscle injury, including rhabdomyolysis, is <0.1%, and the risk of serious hepatotoxicity is ≈0.001%. The risk of statin-induced newly diagnosed diabetes mellitus is ≈0.2% per year of treatment, depending on the underlying risk of diabetes mellitus in the population studied. In patients with cerebrovascular disease, statins possibly increase the risk of hemorrhagic stroke; however, they clearly produce a greater reduction in the risk of atherothrombotic stroke and thus total stroke, as well as other cardiovascular events. There is no convincing evidence for a causal relationship between statins and cancer, cataracts, cognitive dysfunction, peripheral neuropathy, erectile dysfunction, or tendonitis. In US clinical practices, roughly 10% of patients stop taking a statin because of subjective complaints, most commonly muscle symptoms without raised creatine kinase. In contrast, in randomized clinical trials, the difference in the incidence of muscle symptoms without significantly raised creatinine kinase in statin-treated compared with placebo-treated participants is <1%, and it is even smaller (0.1%) for patients who discontinued treatment because of such muscle symptoms. This suggests that muscle symptoms are usually not caused by pharmacological effects of the statin. Restarting statin therapy in these patients can be challenging, but it is important, especially in patients at high risk of cardiovascular events, for whom prevention of these events is a priority. Overall, in patients for whom statin treatment is recommended by current guidelines, the benefits greatly outweigh the risks.
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Association of Clinician Knowledge and Statin Beliefs With Statin Therapy Use and Lipid Levels (A Survey of US Practice in the PALM Registry).
Lowenstern, A, Navar, AM, Li, S, Virani, SS, Goldberg, AC, Louie, MJ, Lee, LV, Peterson, ED, Wang, TY
The American journal of cardiology. 2019;(7):1011-1018
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Abstract
Guideline implementation requires clinician knowledge but may be influenced by pre-existing beliefs and biases. We assessed the association of these clinician factors with lipid management following the release of the 2013 American College of Cardiology/American Heart Association cholesterol guidelines. In the PALM registry, 774 clinicians completed a survey to assess their knowledge of the 2013 American College of Cardiology/American Heart Association guidelines, belief in statin benefit, and statin safety concerns. The association of these factors with statin use, statin dosing, and low-density lipoprotein cholesterol (LDL-C) levels were assessed in the 6,839 patients treated by these clinicians between May and November 2015. Overall, 63.9% of clinicians responded to at least 3 out of 4 hypothetical scenarios in concordance with guideline recommendations (good tested knowledge), 88.4% reported belief in statin benefit, and 15.4% raised concerns about statin safety. Belief in statin benefit was more prevalent among cardiologists, who represented 48.8% of the clinicians surveyed, and concerns regarding statin safety were higher among noncardiologists and clinicians in an academic setting. Guideline knowledge was not associated with a difference in statin use (74.1% vs 73.8%, p = 0.84) and achievement of LDL-C level <100 mg/dl (54.7% vs 52.4%, p = 0.07). However, patients treated by clinicians who reported belief in statin benefit were more likely to receive guideline-recommended statin intensity (41.9% vs 36.9%, p = 0.03), whereas patients treated by clinicians expressing statin safety concerns were less likely receive statins of at least guideline-recommended intensity (36.8% vs 42.5%, p = 0.001) and to achieve an LDL-C <100 mg/dl (44.1% vs 56.1%, p <0.001); the latter persisted after multivariable adjustment (odds ratio 0.75, 95% confidence interval 0.63 to 0.89). In conclusion, clinician beliefs regarding benefits and risks of statins were significantly associated with guideline adherence and patients' achieved LDL-C levels, whereas clinician knowledge of guideline recommendations was not.