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Journal of the American College of... Oct 2021
Topics: Anticholesteremic Agents; Ezetimibe; Humans
PubMed: 34620407
DOI: 10.1016/j.jacc.2021.08.029 -
BMJ (Clinical Research Ed.) Feb 2020
Topics: Anticholesteremic Agents; Cardiovascular Diseases; Clinical Trials as Topic; Drug Industry; Humans; Hypercholesterolemia; PCSK9 Inhibitors; Public-Private Sector Partnerships; RNA, Small Interfering; United Kingdom
PubMed: 32071100
DOI: 10.1136/bmj.m579 -
The American Journal of the Medical... May 2022Experimental and clinical studies have conclusively demonstrated that lowering elevated low-density lipoprotein cholesterol levels results in fewer major adverse cardiac... (Review)
Review
Experimental and clinical studies have conclusively demonstrated that lowering elevated low-density lipoprotein cholesterol levels results in fewer major adverse cardiac events. Over the past few decades, statins have become the mainstay of lipid-lowering therapy, contributing significantly to the reduction of lipids, and providing patients with a cost-effective approach. However, with growing evidence in support of combination therapies providing increased benefits to certain patient populations, such as those intolerant to statins, there is an urgent need to investigate the safety and efficacy of alternative lipid-lowering drugs. In this paper, we review the current alternative and adjuvant cholesterol targeting agents. We further discuss the clinical trials that have evaluated the safety and efficacy of these alternative and adjuvant therapies as well as their implications for practical use. These drugs target levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or lipoprotein(a) as treatments for hyperlipidemia and atherosclerotic cardiovascular disease.
Topics: Anticholesteremic Agents; Atherosclerosis; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents
PubMed: 35081404
DOI: 10.1016/j.amjms.2021.12.011 -
Handbook of Experimental Pharmacology 2022The causal relation between elevated levels of LDL-C and cardiovascular disease has been largely established by experimental and clinical studies. Thus, the reduction of...
The causal relation between elevated levels of LDL-C and cardiovascular disease has been largely established by experimental and clinical studies. Thus, the reduction of LDL-C levels is a major target for the prevention of cardiovascular disease. In the last decades, statins have been used as the main therapeutic approach to lower plasma cholesterol levels; however, the presence of residual lipid-related cardiovascular risk despite maximal statin therapy raised the need to develop additional lipid-lowering drugs to be used in combination with or in alternative to statins in patients intolerant to the treatment. Several new drugs have been approved which have mechanisms of action different from statins or impact on different lipoprotein classes.
Topics: Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Proprotein Convertase 9
PubMed: 32350699
DOI: 10.1007/164_2020_361 -
International Journal of Molecular... Mar 2021Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors are a group of drugs whose main mechanism of action is binding to the PCSK-9 molecule, which reduces... (Review)
Review
Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors are a group of drugs whose main mechanism of action is binding to the PCSK-9 molecule, which reduces the degradation of the low-density lipoprotein receptor (LDL-R) and, hence, increases the uptake of low-density lipoprotein cholesterol (LDLc) from the bloodstream as well as reducing its concentration. The effectiveness of three monoclonal antibodies, namely, alirocumab (human IgG1/κ monoclonal antibody, genetically engineered in Chinese hamster ovary cells), evolocumab (the first fully human monoclonal antibody), and bococizumab (humanized mouse antibody), in inhibiting the action of PCSK-9 and reducing LDLc levels has been confirmed. The first two, after clinical trials, were approved by the Food and Drug Administration (FDA) and are used primarily in the treatment of autosomal familial hypercholesterolemia and in cases of statin intolerance. They are currently used both as monotherapy and in combination with statins and ezetimibe to intensify therapy and achieve therapeutic goals following the American Heart Association (AHA) and European Society of Cardiology (ESC) guidelines. However, the lipid-lowering effect is not the only effect of action described by researchers that PCSK-9 inhibitors have. This paper is a review of the literature describing the pleiotropic effects of PCSK-9 inhibitors, which belong to a group of drugs that are being increasingly used, especially when standard lipid-lowering therapy fails. The article focuses on activities other than lipid-lowering, such as the anti-atherosclerotic effect and stabilization of atherosclerotic plaque, the anti-aggregation effect, the anticoagulant effect, the antineoplastic effect, and the ability to influence the course of bacterial infections. In this publication, we try to systematically review the current scientific data, both from our own scientific work and knowledge from international publications.
Topics: Animals; Anti-Bacterial Agents; Anticholesteremic Agents; Anticoagulants; Antineoplastic Agents; Blood Coagulation; Humans; PCSK9 Inhibitors; Plaque, Atherosclerotic; Protease Inhibitors; Protein Aggregation, Pathological
PubMed: 33808697
DOI: 10.3390/ijms22063144 -
Current Opinion in Lipidology Dec 2023This article reviews PCSK9 inhibitors (PCSK9i) with a focus on clinically relevant studies published in the last 18 months. (Review)
Review
PURPOSE OF REVIEW
This article reviews PCSK9 inhibitors (PCSK9i) with a focus on clinically relevant studies published in the last 18 months.
RECENT FINDINGS
Prespecified subgroup evaluations, secondary analyses, and open-label extension studies from the two landmark trials, FOURIER and ODYSSEY Outcomes, have provided new data on the safety and efficacy of the monoclonal PCSK9 antibodies evolocumab and alirocumab. Recent studies of PCSK9i early in ACS and post percutaneous coronary intervention have explored early effects on biomarkers and plaque morphology with various imaging modalities. Two large outcome trials with PCSK9i in lower risk patients without prior myocardial infarction or stroke are ongoing and could expand the eligible population for these potent therapies. Additionally, novel methods to inhibit PCSK9 using oral administration, vaccination, and gene therapy are in various stages of clinical development.
SUMMARY
PCSK9i represent a potent class of lipid-lowering therapies that are well tolerated and effective in a wide group of patients with high-risk atherosclerotic cardiovascular disease. Ongoing studies of PCSK9i in patients at lower risk and with acute myocardial infarction have the potential to broaden their indication. Alternative methods of PCSK9i are being evaluated and could provide easier and less expensive options for this important class of medication.
Topics: Humans; Anticholesteremic Agents; Proprotein Convertase 9; PCSK9 Inhibitors; Antibodies, Monoclonal; Myocardial Infarction; Cardiovascular Diseases
PubMed: 37606894
DOI: 10.1097/MOL.0000000000000897 -
Current Opinion in Cardiology Jul 2020Lipid-lowering therapies play a major role in reducing atherosclerotic cardiovascular disease (ASCVD). This article reviews the most recent lipid-lowering therapy... (Review)
Review
PURPOSE OF REVIEW
Lipid-lowering therapies play a major role in reducing atherosclerotic cardiovascular disease (ASCVD). This article reviews the most recent lipid-lowering therapy trials, many of which provide a unique opportunity to further reduce low-density lipoprotein cholesterol (LDL-C) levels and ASCVD risk on top of statin therapy, and in doing so further decrease the number of future major adverse cardiovascular events.
RECENT FINDINGS
Although statin therapy has been the mainstay of treatment for lowering LDL-C levels for many years, many individuals require additional or alternative options for further reducing their risk. Trials on previously studied therapies, such as PCSK9 inhibitors, and new therapies, including inclisiran, bempedoic acid and icosapent ethyl demonstrate significant potential for further lowering of LDL-C levels and risk for events on top of maximally tolerated statin therapy with favourable side effect profiles.
SUMMARY
As therapies for ASCVD prevention continue to emerge, clinicians will need to identify the appropriate treatment for individuals based on their estimated risk and risk-enhancing factors. When statin therapy is either not sufficient or patients do not tolerate adequate statin therapy, relying on newer therapies, such as PCSK9-inhibitors, inclisiran, bempedoic acid and icosapent ethyl, will be critical to maximize risk factor profiles to reduce adverse outcomes.
Topics: Anticholesteremic Agents; Cholesterol, LDL; Clinical Trials as Topic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Proprotein Convertase 9
PubMed: 32412963
DOI: 10.1097/HCO.0000000000000757 -
Clinica Chimica Acta; International... Mar 2021Dyslipidemia is correlated with a series of health problems, such as obesity, insulin resistance, and the development of cardiovascular disease (CVD). Currently,... (Review)
Review
Dyslipidemia is correlated with a series of health problems, such as obesity, insulin resistance, and the development of cardiovascular disease (CVD). Currently, accumulating evidence sheds light on the fact that β-hydroxy β-methylglutaryl-CoA reductase inhibitors, named statins, could lower circulating lipid-density lipoprotein cholesterol (LDL-C) and represent a revolution for the prevention of metabolic disorder diseases. In addition, statins remain the cornerstone of LDL-C-lowering treatments, together with ezetimibe and bile acid sequestrants, which are used either in combination with statins or as monotherapies in the case of statin intolerance or side effects. On the other hand, other medicines that reduce circulating LDL-C have also been researched, including inhibitors of protein convertase subtilisin/kexin type 9 (PCSK9). More recently, PCSK9 inhibitors have been approved for the secondary prevention of CVD and for the atherogenic dyslipidemia therapy. Here, we summarize the latest guidelines for the management of dyslipidemia and its relation to CVD, focusing on LDL-C-lowering medicines that are either available in daily clinical practice or under investigation. In addition, we also discuss the "who, when, and how" with respect to treating patients with dyslipidemia according to LDL-C reduction as an individualized clinical precision medicine.
Topics: Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Dyslipidemias; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Precision Medicine; Proprotein Convertase 9
PubMed: 33359059
DOI: 10.1016/j.cca.2020.12.019 -
European Journal of Internal Medicine Jun 2023The relative risk reduction of cardiovascular events is proportional to the absolute reduction in LDL-C levels, the primary target of therapy, no matter the way of... (Review)
Review
The relative risk reduction of cardiovascular events is proportional to the absolute reduction in LDL-C levels, the primary target of therapy, no matter the way of reduction. During the last decades, the therapeutic regimens for reducing the LDL-C levels have been immerged and improved, with favorable effects on the atherosclerotic process and clinical benefits of various cardiovascular outcomes. From a practical view of point, this review is focusing only on the current available lipid lowering agents: statins, ezetimibe, anti PCSK9 monoclonal antibodies, the small interfering RNA (siRNA) agent, Inclisiran, and Bempedoic acid. The recent changes in lipid lowering regimens, including the early combination of lipid lowering agents and "Low LDL-C" levels <30 mg/dL for high/very high cardiovascular risk patients will also be discussed.
Topics: Humans; Cholesterol, LDL; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol; Ezetimibe; Drug Therapy, Combination; Anticholesteremic Agents; Proprotein Convertase 9
PubMed: 36813611
DOI: 10.1016/j.ejim.2023.02.010 -
Revue Medicale Suisse Sep 2022
Topics: Anticholesteremic Agents; Cholesterol, LDL; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 36103125
DOI: 10.53738/REVMED.2022.18.795.1726