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An overview of rosuvastatin/ezetimibe association for the treatment of hypercholesterolemia and mixed dyslipidemia.
Strilchuk, L, Tocci, G, Fogacci, F, Cicero, AFG
Expert opinion on pharmacotherapy. 2020;(5):531-539
Abstract
Introduction: Although statin therapy is a powerful lipid-lowering strategy, only one-fifth of statin users currently reach their lipid goals. In addition, statin treatment alone has relatively low efficacy in reducing other lipid fractions than low-density lipoprotein-cholesterol (LDL-C). In such cases, most guidelines recommend adding the cholesterol absorption inhibitor ezetimibe.Areas covered: This paper summarizes the main pharmacological characteristics of rosuvastatin and ezetimibe (mechanism of action, metabolism), their lipid-lowering and pleiotropic effects, with particular attention to the clinical effects of the combined drugs in hypercholesterolemia and mixed dyslipidemia patients (such as the ones affected by diabetes mellitus and Acquired Immune Deficiency Syndrome (AIDS)).Expert opinion: The additive effect of rosuvastatin and ezetimibe helps to reach lipid goals in a large number of high-risk patients, while avoiding some safety issues related to high dosages of intensive statin therapy. Patients with diabetes receive additional benefits from ezetimibe as they seem to absorb cholesterol more effectively than non-diabetic ones, because of increased NPC1L1 gene expression. Ezetimibe augments rosuvastatin triglyceride-lowering and anti-inflammatory effects, as well. Taking into account its excellent safety profile and lack of clinically relevant drug-drug interactions, the rosuvastatin/ezetimibe association is a valuable alternative to statin dose uptitration.
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Pragmatic Analysis of Dyslipidemia Involvement in Coronary Artery Disease: A Narrative Review.
Mihăilă, RG
Current cardiology reviews. 2020;(1):36-47
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Abstract
BACKGROUND Dyslipidemia is the main factor involved in the occurrence and progression of coronary artery disease. OBJECTIVE The research strategy is aimed at analyzing new data on the pathophysiology of dyslipidemia involvement in coronary artery disease, the modalities of atherogenic risk estimation and therapeutic advances. METHODS Scientific articles published in PubMed from January 2017 to February 2018 were searched using the terms "dyslipidemia" and "ischemic heart disease". RESULTS PCSK9 contributes to the increase in serum levels of low-density lipoprotein-cholesterol and lipoprotein (a). The inflammation is involved in the progression of hyperlipidemia and atherosclerosis. Hypercholesterolemia changes the global cardiac gene expression profile and is thus involved in the increase of oxidative stress, mitochondrial dysfunction, and apoptosis initiated by inflammation. Coronary artery calcifications may estimate the risk of coronary events. The cardioankle vascular index evaluates the arterial stiffness and correlates with subclinical coronary atherosclerosis. The carotid plaque score is superior to carotid intima-media thickness for risk stratification in patients with familial hypercholesterolemia and both can independently predict coronary artery disease. The lipoprotein (a) and familial hypercholesterolemia have a synergistic role in predicting the risk of early onset and severity of coronary atherosclerosis. A decrease in atherosclerotic coronary plaque progression can be achieved in patients with plasma LDL-cholesterol levels below 70 mg/dL. A highly durable RNA interference therapeutic inhibitor of PCSK9 synthesis could be a future solution. CONCLUSION The prophylaxis and treatment of coronary artery disease in a dyslipidemic patient should be based on a careful assessment of cardio-vascular risk factors and individual metabolic particularities, so it may be personalized.
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Treatment of dyslipidemia in kidney transplantation.
Ponticelli, C, Arnaboldi, L, Moroni, G, Corsini, A
Expert opinion on drug safety. 2020;(3):257-267
Abstract
Introduction: Lipid disorders are frequent after kidney transplantation (KT) and KT recipients are considered at high- or very-high cardiovascular risk. Among many concurring factors, a major role is played by immunosuppressants.Areas covered: General measures to manage lipid disorders first include physical activity and diet counseling. Modulating the doses of immunosuppressants also improves dyslipidemia. When lipid-lowering drugs are necessary to control elevated plasma cholesterol and/or triglycerides, statins are the cornerstone for managing hypercholesterolemia. However, side-effects (e.g. myopathy, new-onset diabetes, and kidney graft dysfunction) may occur. In these cases, ezetimibe (which does not affect kidney function) alone or on top of statins for the severe cases, is suggested by the most recent Guidelines. Proprotein convertase subtilisin/kexin type9 inhibitors are promising but expensive and their use in KT is still limited.Expert opinion: In KT recipients, statins should be used cautiously. Rather than using high-dose statin in difficult patients, an association with ezetimibe is suggested. While fibrates, niacin, and resins do not play a relevant role due to their erratic efficacy and common side-effects, new lipid-lowering drugs are emerging but their safety and efficacy in KT patients still need to be assessed.
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Statins and PCSK9 inhibitors: A new lipid-lowering therapy.
Gallego-Colon, E, Daum, A, Yosefy, C
European journal of pharmacology. 2020;:173114
Abstract
The clinical benefit of lipid-lowering therapies is to reduce circulating levels of atherogenic particles and to ameliorate the risk of atherosclerotic cardiovascular disease (ASCVD). The completion of two major clinical trials on PCSK9 inhibitors (PCSK9i), the FOURIER and the ODYSSEY outcome trials, has marked the beginning of a new era of lipid-lowering drugs. PCSK9i, evolocumab and alirocumab, are monoclonal antibodies that inactivate the liver proprotein convertase subtilisin kexin 9 (PCSK9). Inhibition of PCSK9 increases the number of low-density lipoprotein (LDL) receptors available leading to a profound reduction in circulating LDL particles. By preventing LDL receptor destruction, PCSK9i as adjunct to statin therapy can reduce LDL-C by 50-60% above that achieved by statin therapy alone. In addition, PCSK9i in combination with high-dose statins may reduce cardiovascular events and all-cause mortality in patients with clinical ASCVD. Based on evidence from clinical trials, the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidemias now include the use of PCSK9i to very high-risk ASCVD patients who are not achieving treatment goals on a maximum tolerated dose of a statin and ezetimibe. However, the cost-effectiveness of PCSK9i therapy is limited to secondary prevention in high-risk patients. This review outlines the main clinical trials leading to a change in the guidelines, clinical practice as well as the future challenges of PCSK9i therapy.
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From Fad to Fact: Evaluating the Impact of Emerging Diets on the Prevention of Cardiovascular Disease.
D'Souza, MS, Dong, TA, Ragazzo, G, Dhindsa, DS, Mehta, A, Sandesara, PB, Freeman, AM, Taub, P, Sperling, LS
The American journal of medicine. 2020;(10):1126-1134
Abstract
Cardiovascular disease remains one of the most prevalent and preventable chronic conditions worldwide. Diet modification is the foundation of cardiovascular disease prevention. Several dietary approaches have emerged to promote better cardiovascular health. The rapid dissemination of anecdotal and observational data through the internet and social media has caused confusion amongst providers and patients. The aim of this comprehensive review is to present objective insights into 2 of today's most popular fad diets: ketogenic diet and intermittent fasting. We will evaluate the performance of these diets based on their impact on cardiovascular risk factors.
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Current Drugs and Nutraceuticals for the Treatment of Patients with Dyslipidemias.
Scognamiglio, M, Costa, D, Sorriento, A, Napoli, C
Current pharmaceutical design. 2019;(1):85-95
Abstract
Coronary heart disease (CHD) remains the leading cause of disability and death in industrialized Countries. Among many conditions, which contribute to the etiology and progression of CHD, the presence of high low density lipoprotein-cholesterol (LDL-C) levels represents the major risk factor. Therefore, the reduction of LDL-C levels plays a key role in the management of patients with high or very high cardiovascular risk. Although statins represent the gold standard therapy for the reduction of cholesterol levels, these drugs do not allow to achieve target levels of LDL-C in all patients. Indeed, a significant number of patients resulted intolerants, especially when the dosage increased. The availability of new lipid-lowering drugs, such as ezetimibe and PCSK9 inhibitors, may represent an important alternative or complement to the conventional lipid-lowering therapies. However, long-term studies are still needed to define both efficacy and safety of use of these latter new drugs. Some nutraceuticals may become an adequate and effective support in the management of some patients. To date, several nutraceuticals with different mechanism of actions that provide a good tolerability are available as lipidlowering agents. In particular, the most investigated are red yeast rice, phytosterols, berberine, beta-glucans and soy. The aim of this review was to report recent data on the efficacy and safety of principle hypocholesterolemic drugs available and to evaluate the possible role of some nutraceuticals as support therapy in the management of patients with dyslipidemias.
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7.
Lipotoxicity in Kidney, Heart, and Skeletal Muscle Dysfunction.
Nishi, H, Higashihara, T, Inagi, R
Nutrients. 2019;(7)
Abstract
Dyslipidemia is a common nutritional and metabolic disorder in patients with chronic kidney disease. Accumulating evidence supports the hypothesis that prolonged metabolic imbalance of lipids leads to ectopic fat distribution in the peripheral organs (lipotoxicity), including the kidney, heart, and skeletal muscle, which accelerates peripheral inflammation and afflictions. Thus, lipotoxicity may partly explain progression of renal dysfunction and even extrarenal complications, including renal anemia, heart failure, and sarcopenia. Additionally, endoplasmic reticulum stress activated by the unfolded protein response pathway plays a pivotal role in lipotoxicity by modulating the expression of key enzymes in lipid synthesis and oxidation. Here, we review the molecular mechanisms underlying lipid deposition and resultant tissue damage in the kidney, heart, and skeletal muscle, with the goal of illuminating the nutritional aspects of these pathologies.
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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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Statins an oft-prescribed drug is implicated in peripheral neuropathy: The time to know more.
Al-Kuraishy, HM, Al-Gareeb, AI, Hussien, NR, Al-Naimi, MS, Rasheed, HA
JPMA. The Journal of the Pakistan Medical Association. 2019;(8):S108-S112
Abstract
Statins are hydroxymethylglutaryl-coenzyme A reductase inhibitors inhibit denovo cholesterol synthesis leading to reduction of serum cholesterol and low density lipoprotein as well as elevation of high density lipoprotein level. Statins are used in the treatment of dyslipidaemia, prevention of major cardiovascular events and complications. The potential role of statins in the induction of peripheral neuropathy has not been verified as most of statins induced-peripheral neuropathy had been reported as case reports. Also, statins therapy leads to noteworthy reduction of Coenzyme Q10, causing impairment of neuronal energy. The incidence of polyneuropathy was high with atorvastatin (65%) which is lipophilic, and relatively less with fluvastatin (54%) which is hydrophilic. Long-term statins therapy, mainly with atorvastatin and simvastatin, is linked with thedevelopment of peripheral neuropathy.
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10.
[PCSK9 inhibitors: What place in the management of dyslipidemia?].
Sabouret, P, Farnier, M, Puymirat, E
Presse medicale (Paris, France : 1983). 2019;(3 Pt 1):227-237
Abstract
PCSK9 protein is a key regulator of LDL receptor activity. Gain-of-function mutations in PCSK9 are one of the genetic causes of familial hypercholesterolemia. Conversely, loss-of-function mutations are associated with lower levels of LDL cholesterol and reduced coronary heart disease. Monoclonal antibodies targeting PCSK9 are highly efficacious in lowering LDL-C levels, with a good tolerability and safety profile. Two PCSK9 inhibitors, alirocumab and evolocumab, have demonstrated a cardiovascular benefit in addition to statin therapy in patients with established cardiovascular disease. A recent European consensus has defined the candidates for PCSK9 inhibitors, e.g., patients with established cardiovascular disease and patients with familial hypercholesterolemia in primary prevention, with substantially elevated LDL-C levels despite maximally tolerated statin with or without ezetimibe therapy.