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Current Atherosclerosis Reports Dec 2023The purpose of this review is to critically discuss whether more aggressive lipid-lowering strategies are needed in patients with acute coronary syndromes (ACS). (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to critically discuss whether more aggressive lipid-lowering strategies are needed in patients with acute coronary syndromes (ACS).
RECENT FINDINGS
Currently, available data on early (in-hospital/discharge) administration of potent lipid-lowering drugs, such as proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in patients during the vulnerable post-ACS phase, have clearly demonstrated clinical efficacy of the "strike early and strike strong" approach not only for rapid reduction of low-density lipoprotein cholesterol (LDL-C) to unprecedentedly low levels, but also for associated favorable composition of coronary plaque. Intensive lipid-lowering therapy with rapid achievement of the LDL-C treatment goal in ACS patients seems reasonable. However, whether such profound LDL-C reduction would result in additional benefit on the reduction of future CV events still has to be established. Thus, data addressing CV outcomes in such vulnerable patients at extreme CV risk are urgently needed.
Topics: Humans; Proprotein Convertase 9; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Acute Coronary Syndrome; Cholesterol, LDL; Hypolipidemic Agents; Anticholesteremic Agents
PubMed: 38015336
DOI: 10.1007/s11883-023-01163-6 -
European Journal of Preventive... Apr 2020
Topics: Cardiovascular Diseases; Dicarboxylic Acids; Ezetimibe; Fatty Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia
PubMed: 31311303
DOI: 10.1177/2047487319864672 -
International Journal of Molecular... Jul 2023This review aims to examine the complex interaction between dyslipidemia, platelet function, and related drug treatments. In particular, the manuscript provides an... (Review)
Review
This review aims to examine the complex interaction between dyslipidemia, platelet function, and related drug treatments. In particular, the manuscript provides an overview of the effects of major hypolipidemic drugs on platelet function. Indeed, growing evidence supports the view that statins, ezetimibe, PCSK9 inhibitors, inclisiran, and icosapent ethyl also act as antithrombotics. It is known that platelets play a key role not only in the acute phase of coronary syndromes but also in the early phase of atherosclerotic plaque formation. The goal of cholesterol-lowering therapy is to reduce cardiovascular events. The direct effects of cholesterol-lowering drugs are widely described in the literature. Lowering LDL-c (low-density lipoprotein cholesterol) by 1 mmol/L results in a 22-23% reduction in cardiovascular risk. Numerous studies have examined the direct antithrombotic effects of these drugs on platelets, endothelium, monocytes, and smooth muscle cells, and thus, potentially independent of blood LDL-cholesterol reduction. We reviewed in vitro and in vivo studies evaluating the complex interaction between hypercholesterolemia, hypertriglyceridemia, platelet function, and related drug treatments. First, we discussed the role of statins in modulating platelet activation. Discontinuation of statin therapy was associated with increased cardiovascular events with increased ox-LDL, P-selectin, and platelet aggregation. The effect of PCSK9-I (inhibitors of proprotein convertase subtilisin/kexin type 9, PCSK9 involved in the degradation of LDL receptors in the liver) was associated with a statistically significant reduction in platelet reactivity, calculated in P2Y12 reaction units (PRU), in the first 14 days and no difference at 30 days compared to placebo. Finally, in patients with hypertriglyceridemia, the REDUCE-IT study showed that icosapent ethyl (an ethyl ester of eicosapentaenoic acid that reduces triglyceride synthesis and improves triglyceride clearance) resulted in a 25% reduction in ischemic events and cardiovascular death. However, to date, there is not yet clear clinical evidence that the direct antithrombotic effects of the drugs may have a beneficial impact on outcomes independently from the reduction in LDL-C or triglycerides.
Topics: Humans; Anticholesteremic Agents; Atherosclerosis; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Eicosapentaenoic Acid; Ezetimibe; Fibrinolytic Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertriglyceridemia; PCSK9 Inhibitors; Proprotein Convertase 9; Triglycerides
PubMed: 37511498
DOI: 10.3390/ijms241411739 -
Cell Transplantation 2022Although brain tumors occur less frequently than other forms of cancer, they have one of the bleakest prognoses with low survival rates. The conventional treatment for... (Review)
Review
Although brain tumors occur less frequently than other forms of cancer, they have one of the bleakest prognoses with low survival rates. The conventional treatment for brain tumors includes surgery, radiotherapy, and chemotherapy. However, resistance to treatment remains a problem with recurrence shortly following. The resistance to treatment may be caused by cancer stem cells (CSCs), a subset of brain tumor cells with the affinity for self-renewal and differentiation into multiple cell lineages. An emerging approach to targeting CSCs in brain tumors is through repurposing the lipid-lowering medication, lovastatin. Lovastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that impacts the mevalonate pathway. The inhibition of intermediates in the mevalonate pathway affects signaling cascades and oncogenes associated with brain tumor stem cells (BTSC). In this review, we show the possible mechanisms where lovastatin can target BTSC for different varieties of malignant brain tumors.
Topics: Brain; Brain Neoplasms; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lovastatin; Mevalonic Acid
PubMed: 35670207
DOI: 10.1177/09636897221102903 -
Nutrients Mar 2023Cardiovascular diseases (CVD) are the leading cause of death worldwide. Since the establishment of the "lipid hypothesis", according to which, cholesterol level is... (Review)
Review
Cardiovascular diseases (CVD) are the leading cause of death worldwide. Since the establishment of the "lipid hypothesis", according to which, cholesterol level is directly correlated to the risk of CVD, many different lipid-lowering agents have been introduced in clinical practice. A majority of these drugs, in addition to their lipid-lowering properties, may also exhibit some anti-inflammatory and immunomodulatory activities. This hypothesis was based on the observation that a decrease in lipid levels occurs along with a decrease in inflammation. Insufficient reduction in the inflammation during treatment with lipid-lowering drugs could be one of the explanations for treatment failure and recurrent CVD events. Thus, the aim of this narrative review was to evaluate the anti-inflammatory properties of currently available lipid-lowering medications including statins, ezetimibe, bile acid sequestrants (BAS), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, fibrates, omega-3 fatty acids, and niacin, as well as dietary supplements and novel drugs used in modern times.
Topics: Humans; Proprotein Convertase 9; Cholesterol, LDL; Hypolipidemic Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Cardiovascular Diseases; Dietary Supplements; Anticholesteremic Agents
PubMed: 36986246
DOI: 10.3390/nu15061517 -
Annals of Hematology Mar 2024The VEXAS syndrome, a genetically defined autoimmune disease, associated with various hematological neoplasms has been attracting growing attention since its initial...
The VEXAS syndrome, a genetically defined autoimmune disease, associated with various hematological neoplasms has been attracting growing attention since its initial description in 2020. While various therapeutic strategies have been explored in case studies, the optimal treatment strategy is still under investigation and allogeneic cell transplantation is considered the only curative treatment. Here, we describe 2 patients who achieved complete molecular remission of the underlying UBA1 mutant clone outside the context of allogeneic HCT. Both patients received treatment with the hypomethylating agent azacitidine, and deep molecular remission triggered treatment de-escalation and even cessation with sustained molecular remission in one of them. Prospective studies are necessary to clarify which VEXAS patients will benefit most from hypomethylating therapy and to understand the variability in the response to different treatment strategies.
Topics: Humans; Antimetabolites, Antineoplastic; Prospective Studies; Myelodysplastic Syndromes; Azacitidine; Pathologic Complete Response; Skin Diseases, Genetic
PubMed: 38214707
DOI: 10.1007/s00277-023-05611-w -
Biomedicine & Pharmacotherapy =... Sep 2021Statins, typically used to reduce lipid levels, have been rediscovered for exhibiting anticancer activities. Among them, especially simvastatin may influence the... (Review)
Review
Statins, typically used to reduce lipid levels, have been rediscovered for exhibiting anticancer activities. Among them, especially simvastatin may influence the proliferation, migration, and survival of cancer cells. The concept of using statins to treat cancer has been adopted since the 1990s In vitro and in vivo experiments and cohort studies using statins have been carried out to demonstrate their antitumor effects (such as proliferation and migration impairment) by influencing inflammatory and oxidative stress-related tumorigenesis. Nevertheless, the biological mechanisms for these actions are not fully elucidated. In this review, we present an overview of the most important studies conducted from 2015 to date on the use of simvastatin in cancer therapy. This review brings the most recent perspectives and targets in epidemiological, in vitro, and in vivo studies, regarding the use of simvastatin alone or in combination with other drugs for the treatment of various types of cancer.
Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Neoplasms; Simvastatin
PubMed: 34323700
DOI: 10.1016/j.biopha.2021.111858 -
The Korean Journal of Internal Medicine Nov 2023Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), and statins are the primary therapeutic options for reducing low-density... (Review)
Review
Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), and statins are the primary therapeutic options for reducing low-density lipoprotein cholesterol (LDL-C) levels. However, it can be challenging to achieve optimal LDL-C goals with statin monotherapy. Ezetimibe, a cholesterol absorption inhibitor, offers a potential non-statin therapy to optimize LDL-C management. Key clinical trials, such as IMPROVE-IT and RACING, have demonstrated that the addition of ezetimibe to statin therapy leads to further decreases in LDL-C or significant decreases in major adverse cardiovascular events (MACEs), particularly in patients with high ASCVD risk. Subsequent meta-analyses and clinical trials have further supported the beneficial effect of ezetimibe, suggesting additive decreases in LDL-C and MACEs, as well as pleiotropic effects. This review provides a comprehensive analysis of the clinical implications of ezetimibe for managing dyslipidemia; it also evaluates the available evidence that supports the role of ezetimibe as an adjunct non-statin therapy for long-term use. However, the long-term pleiotropic effects of ezetimibe remain controversial because of limited clinical data. Therefore, additional research is needed to clarify its potential benefits beyond LDL-C reduction. Nonetheless, an understanding of the role of ezetimibe in dyslipidemia management will help clinicians to develop effective treatment strategies.
Topics: Humans; Ezetimibe; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol, LDL; Anticholesteremic Agents; Dyslipidemias; Drug Therapy, Combination; Treatment Outcome
PubMed: 37866817
DOI: 10.3904/kjim.2023.243 -
In Vivo (Athens, Greece) 2020Lipid-lowering drugs have been suggested to affect neurocognitive function. This review aimed to give the latest evidence on the way these agents affect neurocognitive... (Review)
Review
BACKGROUND/AIM
Lipid-lowering drugs have been suggested to affect neurocognitive function. This review aimed to give the latest evidence on the way these agents affect neurocognitive function based on clinical trials.
MATERIALS AND METHODS
A systematic search concerning original studies from 2015 to 2020 was performed through the databases PubMed, EMBASE and Cochrane, according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. The trials enrolled numerous patients and were conducted in different areas of the world. The terms used are cholesterol, lipid-lowering drugs, statins and cognitive function.
RESULTS
Eleven randomized trials met the inclusion criteria. The trials included patients suffering from cardiovascular conditions. In particular, patients with coronary heart disease, coronary heart disease risk equivalents and hypercholesterolemia were tested. The trials included evolocumab, alirocumab, statin, ezetimibe or placebo.
CONCLUSION
Lipid-lowering drugs seem to have no significant effect on neurocognitive function, but further research specifically focused on this matter is needed.
Topics: Anticholesteremic Agents; Cholesterol; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Pharmaceutical Preparations
PubMed: 33144414
DOI: 10.21873/invivo.12144 -
Current Cardiology Reports Nov 2019To describe lipid abnormalities in diabetes, when they occur and the evidence base for lipid management with established and new drugs to prevent diabetes complications.... (Review)
Review
PURPOSE OF REVIEW
To describe lipid abnormalities in diabetes, when they occur and the evidence base for lipid management with established and new drugs to prevent diabetes complications. We also discuss how to manage statin intolerance.
RECENT FINDINGS
Statins remain first-line therapy in patients with diabetes, though newer therapies to reduce LDL-C have emerged, including ezetimibe as an add-on therapy to statins, and injectable PCSK9 inhibitors, both of which are safe and effective in diabetes. Emerging evidence suggests a need to consider lipid-lowering therapies more often in younger patients with both type 1 and type 2 diabetes. Statins remain the cornerstone of lipid management in diabetes but other options are increasing. There is also now evidence for better managing apparent statin intolerance. Notably, younger patients lose the most life years from their diabetes, an observation that future guidelines need to consider.
Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dyslipidemias; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents
PubMed: 31758270
DOI: 10.1007/s11886-019-1246-1