DOCSLIB.ORG

News from European Society of Cardiology Aug31-Sept4

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

The future of lipid-lowering drugs Vasculaire geneeskunde ‘From bench to bedside’ 11 september 2020 Hotel Theater Figi, Zeist Jan Albert Kuivenhoven Department of Pediatrics, Section Molecular Genetics University Medical Center Groningen, the Netherlands A current plethora of lipid-lowering drugs...... Registered ACL Five evidence-based drugs HMGCR to reduce LDLc* Treating homozygous familial hypercholesterolemia ∗ INCLIRISAN Treating rare monogenic disorders - lysosomal adic lipase deficiency - familial LCAT deficiency - lipoprotein lipase deficiency - familial chylomicronemia syndrome ∗ Under development NPC1L1 ABE Treating homozygous familial June, 2020 hypercholesterolemia Adapted from HegeleRA, CircRes 2019 ∗ Increasing cellular chol.efflux Phase II & III clinical trials to reduce high Lp(a), Tg, LDLc ∗ * Validated with Mendelian Randomization studies * Bempedoic acid/Ezetimibe - NDA filed Febr 2019 Lipid-lowering drugs • To reduce - LDL cholesterol - reduce atherosclerotic cardiovascular disease (ASCVD) - Triglycerides - ASCVD - severe hypertriglyceridemia - patients witn insulin resistance - Lipoprotein(a) - ASCVD • To treat rare monogenic disorders of lipid metabolism • To modulate steps in the reverse cholesterol pathway to reduce atherosclerosis Managing very severe hypercholesterolemia Extracorporeal removal of lipoproteins Nonspecific plasma exchange / plasmapheresis / specific targeted approaches to remove LDL/Lp(a). No randomized ASCVD outcome trials Block hepatic production of VLDL (precursor of LDL) Mipomersen – antisense oligonucleotide (ASO) against APOB Lomitapide – inhibitor of lipidation of ApoB by microsomal transport protein (MTP) ApoB mRNA Triglycerides - Monoclonal Ab against VLDL ANGPTL3 (Evinakumab) ASO MTP - Gene therapy (ongoing) ApoB protein Lipidation of apoB AAV8.TBG.hLDLR (RGX-501) LDL cholesterol lowering to treat ASCVD Block hepatic cholesterol synthesis Citrate Liver • HMGCR inhibition (statins) LDLR Acetate Citrate Lyase • ACL inhibition (bempedoic acid, Need of Lysosomal functional Acetyl-CoA Nexletol/Nexlizet) (since Febr 2019) degradation LDLc LDLR HMGCR Prevent lysosomal degregation of LDLR LDLR • PCSK9 inhibition - monoclonal antibodies (alirocumab, evolocumab) Cholesterol - antisense oligonucleotide therapy (Inclirisan) - ABE (one time lifelong?) Blocking intestinal cholesterol re-uptake Small Intestine NPC1L1 • NPC1L1 inhibition (ezetimibe) Reduced cholesterol uptake • Bile acid sequestrants (colesevalam) ABCG5/G8 Triglyceride-lowering drugs to treat ASCVD Omega-3 (n-3) fatty acid preparations (‘fish oils’) • Vascepa (eicosapent ethyl). Reduce-it. 25% risk reduction on top of statin therapy. Effects beyond triglycerides anticipated. • Epanova (eicosapentaenoic acid and docosahexaenoic acid) - ongoing Fibrates (PPAR alpha agonists: gemfibrozil/fenofibrate/bezafibrate) • not indicated to treat ASCVD (inconsistent outcome trials – especially in combination with statins) Pemafibrate • Selective PPAR modulator that reduces TG levels by ≤ 45% and improves a wide range of quantitative metabolic subphenotypes, except for LDL-C levels. Large phase III ASCVD trial (Prominent) A new drug to treat (severe) hypertriglyceridemia and possibly insulin resistance Downregulation of apolipoprotein CIII (apoCIII) - familial chylomicronemia syndrome - familial partial lipodystrophy - improving insulin sensitivity ASO (volanesorsen) Monoclonal antibodies (in the works) Phase III trials in 66 FCS patients completed (NEJM 2019; adverse effects) New drugs to possibly treat (severe) dyslipidemia and possibly type 2 diabetes - familial chylomicronemia syndrome Downregulation of angiopoetin-like protein 3 (Angplt3) - familial hypercholesterolemia - lipodystrophies - type 2 diabetes Monoclonal antibodies (Evinakumab) ASO (IONIS-ANGPTL3-LRx (Gal-Nac)) - hypolipidemic effects (Tg, LDLc and HDLc) Hypolipidemic effects in healthy volunteers - reducing LDLc independent of LDLR! with hypertriglyceridemia Phase II trial in - phase III trial completed for FH (NEJM, Raal T2D patients (Jan, 2020) – 90% success Aug, 2020) Promise to lower Lp(a) to reduce atherosclerosis Lp(a) is • atherogenic via its LDL-like moiety • proinflammatory via its OxPL content • antifibrinolytic via its apo(a) moiety Risk factor for both ASCVD and calcific aortic valve disease Mendelian Randomization studies: LPA is causally related to ASCVD PCSK9i lower Lp(a) to a limited extent. ASO: APO(a)LrX. A phase 2 dose-ranging and safety study ongoing in patients with hyperlipoproteinemia[a] and cardiovascular disease; Phase 3 outcomes trial initiated in Dec 2019 (n=7600; Lp(a) above 70mg/dl). Outcome 2024 Current options to treat atherogenic dyslipidemia Decreasing LDLc • statins • ezetimibe • bile acid sequestrants • monoclonal Ab’s against PCSK9 • mipomersen, lomitapide • awaiting ASO against PCSK9 and LDLR gene therapy • ABE against PCSK9 and ANGPTL3 Decreasing triglycerides (remnant cholesterol?) • eicosapent ethyl (Vascepa). Effects not only mediated by moderate Tg reduction? • other fish oil based therapies: Epanova • awaiting outcomes trials to downregulate ApoCIII and Angptl3 Decreasing Lp(a) – hypothesis tested • awaiting outcome trials with ASOs Are these drugs actually used? Adherence to guidelines to prevent cardiovascular diseases: The LifeLines cohort study J W Balder 1, S Scholtens, J K de Vries, L M van Schie, S M Boekholdt, G K Hovingh, P W Kamphuisen, J A Kuivenhoven PMID: 26314714 Results: For primary prevention, 77% (2515 of 3268) of those eligible for LLD treatment did not report using these drugs, while for secondary prevention this was 31% (403 of 1302). Patients with diabetes mellitus were treated best (67%) for primary prevention. Notably, of the patients with stroke, only 47% (182 of 386) reported LLD treatment. Future of novel lipid-lowering drugs. Promising but vulnerable ‘Newcomers’ largely dependent of ACL HMGCR 1. long-term safety of monoclonal antibodies - PCKS9i – alirocumab, INCLIRISAN evolocumab - ANGPTL3 – evinacumab - APOC3 2. efficacy and safety of antisense oligonucleotide (ASO) drugs - PCSK9 - inclirisan NPC1L1 - APOC3 - volanesorsen Adapted from HegeleRA, CircRes 2019 - LPA - APO(a)LRx 3. All are expensive and (as yet) not available to most high risk patients. The future of lipid-lowering drugs – small molecule inhibitors? ACL HMGCR When costs remain a main hurdle INCLIRISAN - bempedoic acid GPR146i - gemcabene - GPR146 antagonists?* GPR146 deficiency protects against hypercholesterolemia and ∗ atherosclerosis. Cell, Nov 27, 2019 NPC1L1 Adapted from HegeleRA, CircRes 2019 ∗ Treating ‘residual atherosclerosis risk’ associated with high TG and low HDLc. Antihyperglycemic agents Glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as 2 new classes of antihyperglycemic agents that also reduce cardiovascular risk in multiple RCT trials. E. J. Northa and J.D. Newman, Curr Opin Cardiol 2019 Zelniker TA et al Circulation. 2019 Treating ‘residual atherosclerosis risk’ associated with high Tg and low HDLc. Guided lifestyle intervention. Alternate Day Fasting Improves Primary care-led weight management for Physiological and Molecular Markers of remission of type 2 diabetes (DiRECT): an Aging in Healthy, Non-obese Humans. open-label, cluster-randomized trial. Mean bodyweight fell by 10·0 kg (SD 8·0) - almost half of participants achieved remission to a non-diabetic state and off antidiabetic drugs Stekovic S. Cell Met 2019, Sept 3. Lean ME, Lancet. 2018 Thoughts associated with the future of lipid-lowering drugs No 1 - Lifestyle advice. Need of governmental intervention. Works! No 2 - Adherence to guidelines with currently available drugs No 3 - Focus on lowest cost drugs with good efficacy Stop the chase for new drugs that are never going to used in the general patient at increased ASCVD risk When combining guided lifestyle interventions with available drugs, we already work towards personalized lipid-lowering therapy Atherosclerosis starts in childhood How should we best proceed? Start early! Treated when clinical events have occured Thank you for your attention! Background literature 1) Hegele RA et al. CircRes 2019 2) Ray K, Lancet, Sept 2019; x< 3) Zwol WV et al J Clin Med. 2019; PMID: 31340607.
Recommended publications
  • Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011

    Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011

    CLASSIFICATION DECISIONS TAKEN BY THE HARMONIZED SYSTEM COMMITTEE FROM THE 47TH TO 60TH SESSIONS (2011 - 2018) WORLD CUSTOMS ORGANIZATION Rue du Marché 30 B-1210 Brussels Belgium November 2011 Copyright © 2011 World Customs Organization. All rights reserved. Requests and inquiries concerning translation, reproduction and adaptation rights should be addressed to [email protected]. D/2011/0448/25 The following list contains the classification decisions (other than those subject to a reservation) taken by the Harmonized System Committee ( 47th Session – March 2011) on specific products, together with their related Harmonized System code numbers and, in certain cases, the classification rationale. Advice Parties seeking to import or export merchandise covered by a decision are advised to verify the implementation of the decision by the importing or exporting country, as the case may be. HS codes Classification No Product description Classification considered rationale 1. Preparation, in the form of a powder, consisting of 92 % sugar, 6 % 2106.90 GRIs 1 and 6 black currant powder, anticaking agent, citric acid and black currant flavouring, put up for retail sale in 32-gram sachets, intended to be consumed as a beverage after mixing with hot water. 2. Vanutide cridificar (INN List 100). 3002.20 3. Certain INN products. Chapters 28, 29 (See “INN List 101” at the end of this publication.) and 30 4. Certain INN products. Chapters 13, 29 (See “INN List 102” at the end of this publication.) and 30 5. Certain INN products. Chapters 28, 29, (See “INN List 103” at the end of this publication.) 30, 35 and 39 6. Re-classification of INN products.
  • N-Acetyl Galactosamine-Conjugated Antisense Drug to APOC3 Mrna, Triglycerides and Atherogenic Lipoprotein Levels

    N-Acetyl Galactosamine-Conjugated Antisense Drug to APOC3 Mrna, Triglycerides and Atherogenic Lipoprotein Levels

    European Heart Journal (2019) 40, 2785–2796 CLINICAL RESEARCH doi:10.1093/eurheartj/ehz209 Lipids N-acetyl galactosamine-conjugated antisense drug to APOC3 mRNA, triglycerides and atherogenic lipoprotein levels Veronica J. Alexander1, Shuting Xia1, Eunju Hurh2, Steven G. Hughes1, Louis O’Dea2, Richard S. Geary1, Joseph L. Witztum3, and Sotirios Tsimikas1,4* 1Ionis Pharmaceuticals, Inc., 2855 Gazelle Ct, Carlsbad, CA 92010, USA; 2Akcea Therapeutics, 22 Boston Wharf Road, 9th Floor, Boston, MA 02210, USA; 3Division of Endocrinology and Metabolism, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0682, USA; and 4Division of Cardiovascular Medicine, Sulpizio Cardiovascular Center, Vascular Medicine Program, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0682, USA Received 15 January 2019; revised 8 March 2019; editorial decision 25 March 2019; accepted 4 April 2019; online publish-ahead-of-print 24 April 2019 See page 2797 for the editorial comment on this article (doi: 10.1093/eurheartj/ehz321) Aims Elevated apolipoprotein C-III (apoC-III) levels are associated with hypertriglyceridaemia and coronary heart disease. AKCEA-APOCIII-LRx is an N-acetyl galactosamine-conjugated antisense oligonucleotide targeted to the liver that selectively inhibits apoC-III protein synthesis. ................................................................................................................................................................................................... Methods The safety, tolerability, and efficacy of AKCEA-APOCIII-LRx was assessed in a double-blind, placebo-controlled, and results dose-escalation Phase 1/2a study in healthy volunteers (ages 18–65) with triglyceride levels >_90 or >_200 mg/dL. Single-dose cohorts were treated with 10, 30, 60, 90, and 120 mg subcutaneously (sc) and multiple-dose cohorts were treated with 15 and 30 mg weekly sc for 6 weeks or 60 mg every 4 weeks sc for 3 months.
  • Statin-Induced Myopathy: Translational Studies from Preclinical to Clinical Evidence

    Statin-Induced Myopathy: Translational Studies from Preclinical to Clinical Evidence

    International Journal of Molecular Sciences Review Statin-Induced Myopathy: Translational Studies from Preclinical to Clinical Evidence Giulia Maria Camerino 1, Nancy Tarantino 1 , Ileana Canfora 1 , Michela De Bellis 1, Olimpia Musumeci 2 and Sabata Pierno 1,* 1 Section of Pharmacology, Department of Pharmacy and Drug Sciences, University of Bari “Aldo Moro”, 70125 Bari, Italy; [email protected] (G.M.C.); [email protected] (N.T.); [email protected] (I.C.); [email protected] (M.D.B.) 2 Unit of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy; [email protected] * Correspondence: [email protected] Abstract: Statins are the most prescribed and effective drugs to treat cardiovascular diseases (CVD). Nevertheless, these drugs can be responsible for skeletal muscle toxicity which leads to reduced compliance. The discontinuation of therapy increases the incidence of CVD. Thus, it is essential to assess the risk. In fact, many studies have been performed at preclinical and clinical level to investigate pathophysiological mechanisms and clinical implications of statin myotoxicity. Conse- quently, new toxicological aspects and new biomarkers have arisen. Indeed, these drugs may affect gene transcription and ion transport and contribute to muscle function impairment. Identifying a marker of toxicity is important to prevent or to cure statin induced myopathy while assuring the right therapy for hypercholesterolemia and counteracting CVD. In this review we focused on the mechanisms of muscle damage discovered in preclinical and clinical studies and highlighted the Citation: Camerino, G.M.; Tarantino, pathological situations in which statin therapy should be avoided.
  • Volanesorsen Fdaadvisory Committee Meeting Briefing Document

    Volanesorsen Fdaadvisory Committee Meeting Briefing Document

    VOLANESORSEN FDA ADVISORY COMMITTEE MEETING BRIEFING DOCUMENT ENDOCRINE AND METABOLIC DRUGS ADVISORY COMMITTEE MEETING DATE: 10 MAY 2018 ADVISORY COMMITTEE BRIEFING MATERIALS: AVAILABLE FOR PUBLIC RELEASE Volanesorsen (ISIS 304801) Akcea Therapeutics Endocrine and Metabolic Drugs Advisory Committee Briefing Document 10 May 2018 Meeting TABLE OF CONTENTS TABLE OF CONTENTS .................................................................................................................2 TABLE OF TABLES ......................................................................................................................6 TABLE OF FIGURES .....................................................................................................................9 LIST OF ABBREVIATIONS ........................................................................................................10 1. EXECUTIVE SUMMARY ........................................................................................11 1.1 Familial Chylomicronemia Syndrome ........................................................................12 1.1.1 Overview of the Disease and Impact of Elevated Triglyceride Levels ......................12 1.1.2 Current Treatment Options .........................................................................................14 1.2 Volanesorsen Clinical Development Program ............................................................15 1.3 Efficacy and Safety of Volanesorsen ..........................................................................15
  • Anatomical Classification Guidelines V2021 EPHMRA ANATOMICAL CLASSIFICATION GUIDELINES 2021

    Anatomical Classification Guidelines V2021 EPHMRA ANATOMICAL CLASSIFICATION GUIDELINES 2021

    EPHMRA ANATOMICAL CLASSIFICATION GUIDELINES 2021 Anatomical Classification Guidelines V2021 "The Anatomical Classification of Pharmaceutical Products has been developed and maintained by the European Pharmaceutical Marketing Research Association (EphMRA) and is therefore the intellectual property of this Association. EphMRA's Classification Committee prepares the guidelines for this classification system and takes care for new entries, changes and improvements in consultation with the product's manufacturer. The contents of the Anatomical Classification of Pharmaceutical Products remain the copyright to EphMRA. Permission for use need not be sought and no fee is required. We would appreciate, however, the acknowledgement of EphMRA Copyright in publications etc. Users of this classification system should keep in mind that Pharmaceutical markets can be segmented according to numerous criteria." © EphMRA 2021 Anatomical Classification Guidelines V2021 CONTENTS PAGE INTRODUCTION A ALIMENTARY TRACT AND METABOLISM 1 B BLOOD AND BLOOD FORMING ORGANS 28 C CARDIOVASCULAR SYSTEM 36 D DERMATOLOGICALS 51 G GENITO-URINARY SYSTEM AND SEX HORMONES 58 H SYSTEMIC HORMONAL PREPARATIONS (EXCLUDING SEX HORMONES) 68 J GENERAL ANTI-INFECTIVES SYSTEMIC 72 K HOSPITAL SOLUTIONS 88 L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS 96 M MUSCULO-SKELETAL SYSTEM 106 N NERVOUS SYSTEM 111 P PARASITOLOGY 122 R RESPIRATORY SYSTEM 124 S SENSORY ORGANS 136 T DIAGNOSTIC AGENTS 143 V VARIOUS 145 Anatomical Classification Guidelines V2021 INTRODUCTION The Anatomical Classification was initiated in 1971 by EphMRA. It has been developed jointly by Intellus/PBIRG and EphMRA. It is a subjective method of grouping certain pharmaceutical products and does not represent any particular market, as would be the case with any other classification system.
  • Stembook 2018.Pdf

    Stembook 2018.Pdf

    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
  • NLA-TG Therapies DIXON

    NLA-TG Therapies DIXON

    Therapeutic Options for Triglyceride Lowering Dave L. Dixon, PharmD, BCPS, CDE, CLS, AACC, FNLA Associate Professor and Vice-Chair of Clinical Services Department of Pharmacotherapy & Outcomes Science Disclosures • Novartis – Speaker’s Bureau • Sanofi – Received speaker honorarium Objectives • Summarize current guideline recommendations on the management of hypertriglyceridemia. • Compare and contrast the safety, efficacy, and tolerability of available lipid-lowering therapies that lower triglycerides. • Discuss emerging triglyceride-lowering therapies. AHA Scientific Statement: Triglycerides and Cardiovascular Disease Fasting Triglyceride Level (mg/dL) Recommendations 150-199 200-499 ≥500* Weight Loss Up to 5% 5-10% 5-10% Carbohydrates 50-60% 50-55% 45-50% • Added sugar <10% 5-10% <5% • Fructose <100g 50-100g <50g Protein 15% 15-20% 20% Fat 25-35% 30-35% 30-35% • Trans Avoid Avoid Avoid • Saturated <7% <5% <5% • Monounsaturated 10-20% 10-20% 10-20% • Polyunsaturated 10-20% 10-20% 10-20% • EPA/DHA 0.5-1 g 1-2g >2g Aerobic Activity At least 2 times weekly * Drug therapy to prevent pancreatitis Circulation. 2011;123:2292-2333 ACC/AHA Cholesterol Guideline • Reader directed to the 2011 AHA Scientific Statement on TG (see previous slide) • Treatment of elevated TG listed as a critical question for consideration in future guideline updates… Circulation. 2014;129[suppl 2]:S1:S45. NLA Recommendations • TG >1000 mg/dL – Primary goal: reduce pancreatitis risk – TG-lowering therapy O3FA, fibrates, or niacin • TG 500-999 mg/dL – Primary goal: reduce pancreatitis risk – Statin monotherapy “OK” if no h/o pancreatitis – O3FA, fibrates, or niacin preferred as initial therapy in patients with h/o pancreatitis J Clin Lipidol.
  • The Importance of Lipoprotein Lipase Regulationin Atherosclerosis

    The Importance of Lipoprotein Lipase Regulationin Atherosclerosis

    biomedicines Review The Importance of Lipoprotein Lipase Regulation in Atherosclerosis Anni Kumari 1,2 , Kristian K. Kristensen 1,2 , Michael Ploug 1,2 and Anne-Marie Lund Winther 1,2,* 1 Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen N, Denmark; Anni.Kumari@finsenlab.dk (A.K.); kristian.kristensen@finsenlab.dk (K.K.K.); m-ploug@finsenlab.dk (M.P.) 2 Biotech Research and Innovation Centre (BRIC), University of Copenhagen, DK-2200 Copenhagen N, Denmark * Correspondence: Anne.Marie@finsenlab.dk Abstract: Lipoprotein lipase (LPL) plays a major role in the lipid homeostasis mainly by mediating the intravascular lipolysis of triglyceride rich lipoproteins. Impaired LPL activity leads to the accumulation of chylomicrons and very low-density lipoproteins (VLDL) in plasma, resulting in hypertriglyceridemia. While low-density lipoprotein cholesterol (LDL-C) is recognized as a primary risk factor for atherosclerosis, hypertriglyceridemia has been shown to be an independent risk factor for cardiovascular disease (CVD) and a residual risk factor in atherosclerosis development. In this review, we focus on the lipolysis machinery and discuss the potential role of triglycerides, remnant particles, and lipolysis mediators in the onset and progression of atherosclerotic cardiovascular disease (ASCVD). This review details a number of important factors involved in the maturation and transportation of LPL to the capillaries, where the triglycerides are hydrolyzed, generating remnant lipoproteins. Moreover, LPL and other factors involved in intravascular lipolysis are also reported to impact the clearance of remnant lipoproteins from plasma and promote lipoprotein retention in Citation: Kumari, A.; Kristensen, capillaries. Apolipoproteins (Apo) and angiopoietin-like proteins (ANGPTLs) play a crucial role in K.K.; Ploug, M.; Winther, A.-M.L.
  • Emerging New Lipid-Lowering Therapies in the Statin Era

    Emerging New Lipid-Lowering Therapies in the Statin Era

    Cardiometab Syndr J. 2021 Mar;1(1):66-75 https://doi.org/10.51789/cmsj.2021.1.e5 pISSN 2734-1143·eISSN 2765-3749 View Point Emerging New Lipid-Lowering Therapies in the Statin Era Albert Youngwoo Jang , MD1, Sang-Ho Jo , MD, PhD2, and Kwang Kon Koh, MD, PhD1 1Division of Cardiovascular Disease, Gachon Cardiovascular Research Institute, Gachon University Gil Hospital, Incheon, Korea 2Cardiovascular Center, Hallym University Sacred Heart Hospital, Anyang, Korea Received: Dec 18, 2020 Revised: Jan 12, 2021 ABSTRACT Accepted: Jan 17, 2021 Statins have become the backbone of lipid-lowering therapy today by dramatically improving Correspondence to cardiovascular (CV) outcomes. Despite well-controlled low-density lipoprotein cholesterol Kwang Kon Koh, MD, PhD (LDL-C) through statins, up to 40% patients still experience CV diseases. New therapeutic Cardiometabolic Syndrome Unit, Division of Cardiology, Gachon University Gil Hospital, 774 agents to target such residual cholesterol risk by lowering not only LDL-C but triglyceride beon-gil 21, Namdong-daero, Namdong-gu, (TG), TG-rich lipoproteins (TRL), or lipoprotein(a) (Lp[a]) are being newly introduced. Incheon 21565, Korea. Proprotein convertase subtilisin/kexin type 9 (PCSK9) small interference RNA (siRNA) and E-mail: [email protected] bempedoic acid therapies adding to statin therapies have shown additional improvement Copyright © 2021. Korean Society of in CV outcomes. Recent trials investigating eicosapentaenoic acid to patients with high CardioMetabolic Syndrome TG despite statin therapy have also demonstrated significant CV benefit. Antisense This is an Open Access article distributed oligonucleotide (ASO) therapies with hepatocyte-specific targeting modifications are now under the terms of the Creative Commons being newly introduced with promising lipid-lowering effects.
  • ATC-Index Mit DDD-Angaben Für Deutschland Im Jahr 2020

    ATC-Index Mit DDD-Angaben Für Deutschland Im Jahr 2020

    Fehler! Kein Text mit angegebener Formatvorlage im Dokument. 1 Uwe Fricke – Judith Günther - Katja Niepraschk- von Dollen – Anette Zawinell Mai 2020 Anatomisch-therapeutisch- chemische Klassifikation mit Tagesdosen für den deutschen Arzneimittelmarkt ATC-Index mit DDD-Angaben GKV-Arzneimittelindex Impressum Die vorliegende Publikation ist ein Beitrag des GKV-Arzneimittelindex im Wissenschaftlichen Institut der AOK (WldO). Anatomisch-therapeutisch-chemische Klassifikation mit Tagesdosen für den deutschen Arzneimittelmarkt ATC-Index mit DDD-Angaben für den deutschen Arzneimittelmarkt Berlin 2020, 19. überarbeitete Auflage Uwe Fricke, Judith Günther, Katja Niepraschk-von Dollen, Anette Zawinell Wissenschaftliches Institut der AOK (WldO) im AOK-Bundesverband GbR Rosenthaler Str. 31, 10178 Berlin Geschäftsführender Vorstand: Martin Litsch (Vorsitzender) Jens Martin Hoyer (stellv. Vorsitzender) http://www.aok-bv.de/impressum/index.html Aufsichtsbehörde: Senatsverwaltung für Gesundheit, Pflege und Gleichstellung –SenGPG– Oranienstraße 106, 10969 Berlin Pharmazeutisch-technische Assistenz: Sandra Heric, Heike Hoffmeister, Sabine Roggan, Manuela Steden Datenverarbeitung: Kenan Ajanovic, Birol Knecht Redaktionelle Bearbeitung: Melanie Hoberg, Manuela Steden Umschlaggestaltung/Design: KomPart Nachdruck, Wiedergabe, Vervielfältigung und Verbreitung (gleich welcher Art), auch von Teilen des Werkes, bedürfen der ausdrücklichen Genehmigung. E-Mail: [email protected] Internet: http://www.wido.de Inhalt Wissenschaftliche Berater des GKV-Arzneimittelindex

  • Waylivra, Volanesorsen

    ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions. 1. NAME OF THE MEDICINAL PRODUCT Waylivra 285 mg solution for injection in pre-filled syringe 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each ml contains 200 mg volanesorsen sodium, equivalent to 190 mg volanesorsen. Each single-dose pre-filled syringe contains 285 mg of volanesorsen in 1.5 ml solution. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Solution for injection (injection). Clear, colourless to slightly yellow solution with a pH of approximately 8 and osmolarity of 363-485 mOsm/kg. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Waylivra is indicated as an adjunct to diet in adult patients with genetically confirmed familial chylomicronemia syndrome (FCS) and at high risk for pancreatitis, in whom response to diet and triglyceride lowering therapy has been inadequate. 4.2 Posology and method of administration Posology Treatment should be initiated by and remain under the supervision of a physician experienced in the treatment of patients with FCS. Prior to initiating Waylivra, secondary causes of hypertriglyceridemia (e.g. uncontrolled diabetes, hypothyroidism) should be excluded or appropriately addressed. The recommended starting dose is 285 mg in 1.5 ml injected subcutaneously once weekly for 3 months. Following 3 months, dose frequency should be reduced to 285 mg every 2 weeks. However, treatment should be discontinued in patients with a reduction in serum triglycerides <25% or who fail to achieve serum triglycerides below 22.6 mmol/L after 3 months on volanesorsen 285 mg weekly.

  • The Future of Lipid-Lowering Therapy Willemien Van Zwol, Antoine Rimbert, Jan Kuivenhoven

    The Future of Lipid-Lowering Therapy Willemien Van Zwol, Antoine Rimbert, Jan Kuivenhoven To cite this version: Willemien Van Zwol, Antoine Rimbert, Jan Kuivenhoven. The Future of Lipid-Lowering Therapy. Journal of Clinical Medicine, MDPI, 2019, 8 (7), pp.1085. 10.3390/jcm8071085. hal-02422745 HAL Id: hal-02422745 https://hal.archives-ouvertes.fr/hal-02422745 Submitted on 23 Dec 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Journal of Clinical Medicine Review The Future of Lipid-Lowering Therapy Willemien van Zwol, Antoine Rimbert and Jan Albert Kuivenhoven * Department of Pediatrics, Section Molecular Genetics, University of Groningen, University Medical Centre Groningen, 9713 Groningen, The Netherlands * Correspondence: [email protected]; Tel.: +31-50-3637932 Received: 2 July 2019; Accepted: 22 July 2019; Published: 23 July 2019 Abstract: The recent introduction of inhibitors of proprotein convertase subtilisin/kexin 9 to lower low-density lipoprotein (LDL) cholesterol on top of statins or as monotherapy is rapidly changing the landscape of treatment of atherosclerotic cardiovascular disease (ASCVD). However, existing lipid-lowering drugs have little impact on lipoprotein(a) (Lp(a)) or plasma triglycerides, two other risk factors for ASCVD.