Cardiovascular Risk CME ACCREDITED Watch Time: 36 mins

touchPANEL DISCUSSION Current and future management of hyperlipidaemia and atherosclerosis: From statins to combination therapy

Watch an expert panel discuss cholesterol-lowering regimens in the management of hyperlipidaemia and atherosclerosis.

Prof. Alberico Catapano

University of Milan, Milan, Italy

CHAIR

Panelists:
Dr Jacques Genest, Prof. Kausik Ray
 
Video Chapters
Introduction

Professor of Pharmacology Alberico Catapano (Chair) introduces the panel comprising a Professor of Medicine and a Professor of Public Health, both involved in the management of patients with hyperlipidaemia.

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Video Chapters
What is the impact of statins on lipidaemia and what are their limitations?

The expert panel discuss the varying effects of statins in the prevention of atherosclerotic cardiovascular disease and consider issues of tolerability and non-adherence that limit their use.

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Video Chapters
When is monotherapy with statins no longer sufficient?

In this discussion, the panel reviews regional guidelines for therapeutic target-setting with statin monotherapy and share their experiences about when to progress patients on to second-line therapy.

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Video Chapters
What are the advantages of combination therapy and when should it be considered?

The panel considers both the evidence and guideline recommendations for additional therapy using ezetimibe and/or PCSK9 inhibitors in patients who are not achieving LDL-C goals with statin monotherapy.

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Overview & Learning Objectives
Overview

In this activity, cardiology experts discuss the current and future management of hyperlipidaemia and atherosclerosis.

This activity has been jointly provided by Oakstone Publishing, touchCARDIO and touchENDOCRINOLOGY. Oakstone Publishing is accredited by the ACCME to provide continuing medical education to physicians.

Target audience

This activity has been designed to meet the educational needs of cardiologists, endocrinologists and primary care physicians involved in the management of hyperlipidaemia and atherosclerosis.

Disclosures

Faculty

Oakstone Publishing has assessed conflict of interest with its faculty, authors, editors, and any individuals who were in a position to control the content of this CME activity. Any identified relevant conflicts of interest were resolved for fair balance and scientific objectivity of studies utilized in this activity. Oakstone Publishing’s planners, content reviewers, and editorial staff disclose no relevant commercial interests.

Prof. Alberico Catapano discloses: Grant and research support from Amgen, Eli Lilly and Company, Menarini, Mylan, Sanofi and Sanofi Regeneron. Consultancy/Advisory board fees from Aegerion, Akcea Therapeutics, Amgen, Daiichi Sankyo, Esperion Therapeutics, Genzyme, Ionis Pharmaceuticals, Kowa Pharmaceuticals, Menarini, Merck and Co., Inc., Mylan, Novartis, Recordati, Regeneron Pharmaceuticals, Sandoz and Sanofi. Speaker Bureau fees from Akcea Therapeutics, Amgen, Daiichi Sankyo, Esperion Therapeutics, Ionis Pharmaceuticals, Kowa Pharmaceuticals, Menarini, Merck and Co., Inc., Mylan, Novartis, Recordati, Regeneron Pharmaceuticals and Sanofi.

Dr Jacques Genest discloses: Grant and research support from the Canadian Institutes of Health Research and FH Canada (Chair). Consultancy fees from Amgen and Sanofi.

Prof. Kausik Ray discloses: Grant and research support from Amgen, Daiichi Sankyo, MSD, Pfizer, Regeneron Pharmaceuticals and Sanofi. Consultancy/Advisory board fees from AbbVie, Akcea Therapeutics, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cerenis Therapeutics, Eli Lilly and Company, Esperion Therapeutics, Ionis Pharmaceuticals, Kowa Pharmaceuticals, MedCo, MSD, NewAmsterdam Pharma, Novartis, Novo Nordisk, Pfizer, Regeneron Pharmaceuticals, Sanofi, Takeda and The Medicines Company. Speaker Bureau fees from Amgen, AstraZeneca, Boehringer Ingelheim, Cipla, Dr Reddy’s Laboratories Ltd., Novo Nordisk, Pfizer, Sanofi and Zuellig Pharma. Honorarium/Honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Kowa Pharmaceuticals, Novo Nordisk, Pfizer and Sanofi. Stock options in Pemi31 Therapeutics, Inc.

Content Reviewer

Walter Murray Yarbrough, MD, has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Sola Neunie has no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Oakstone Publishing and touchIME. Oakstone Publishing is accredited by the ACCME to provide continuing medical education for physicians.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 Credit™ into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

Oakstone Publishing designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

In order to receive credit for this activity, participants must review and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

Date of original release: 15 December 2020. Date credits expire: 15 December 2021.
Learning Objectives

After watching this activity participants should be better able to:

  • Recall the current standard of care for cholesterol-lowering therapy and the potential limitations of statin monotherapy
  • Discuss the clinical considerations which guide the choice of second-line or add-on therapy when statin monotherapy is ineffective or not tolerated
  • Summarize the most recent data on the effect of dual lipid-lowering therapy on hyperlipidaemia and the risk for atherosclerosis
Faculty & Disclosures
Prof. Alberico Catapano

University of Milan, Milan, Italy

Alberico Catapano is Full Professor of Pharmacology and Director of the Centre of Epidemiology and Preventive Pharmacology at the University of Milan, as well as Director of the Laboratory of Lipoproteins, Immunity and Atherosclerosis and the Centre for the Study of Atherosclerosis at Bassini Hospital, and at MultiMedica IRCCS Milan, Italy.

His main research interests include the study of atherosclerosis, lipids, lipoproteins and genetic dyslipidaemias. He has made landmark observations regarding heat-shock proteins and pentraxins in atherogenesis, on high-density lipoproteins in the modulation of the immune response, and on the identification of possible therapeutic targets by exploiting genetic information.

A past President of the European Atherosclerosis Society (EAS), Prof. Catapano is currently Co-Chairman of the EAS/European Society of Cardiology (ESC) guidelines for the treatment of dyslipoproteinaemias, President of the Italian Society of Clinical and  Experimental Therapy, and a board member of the Italian Society for the Study of Atherosclerosis (SISA), as well as the General Director of the SISA Foundation. He is also an editor of Atherosclerosis Supplements, co-editor of Atherosclerosis and associate editor of other scientific journals. He has authored more than 460 scientific papers in peer-reviewed journals and is among the most highly cited scientists in 2019, according to Clarivate.

Prof. Alberico Catapano discloses: Grant and research support from Amgen, Eli Lilly and Company, Menarini, Mylan, Sanofi and Sanofi Regeneron. Consultancy/Advisory board fees from Aegerion, Akcea Therapeutics, Amgen, Daiichi Sankyo, Esperion Therapeutics, Genzyme, Ionis Pharmaceuticals, Kowa Pharmaceuticals, Menarini, Merck and Co., Inc, Mylan, Novartis, Recordati, Regeneron Pharmaceuticals, Sandoz and Sanofi. Speaker Bureau fees from Akcea Therapeutics, Amgen, Daiichi Sankyo, Esperion Therapeutics, Ionis Pharmaceuticals, Kowa Pharmaceuticals, Menarini, Merck and Co., Inc, Mylan, Novartis, Recordati, Regeneron Pharmaceuticals and Sanofi.

Dr Jacques Genest

McGill University Health Center, Montreal, QC, Canada

Jacques Genest has been Professor of Medicine and the McGill/Novartis Chair in Medicine at McGill University since 2000. From 2000 to 2010, he was Head of Cardiology at McGill University and he was Director of the Center for Innovative Medicine at the McGill University Health Center (MUHC) from 2010 to 2014.

Dr Genest’s research focuses on the metabolic and genetic basis of premature coronary artery disease and the role of high-density lipoproteins (HDL) in atherosclerosis. His research team has contributed to the identification of several genes involved in the metabolism of HDL. He has been involved in the design, steering committees and running of several large clinical trials (HOPE-2, homocysteine; JUPITER; REVEAL; IMPROVE-IT and CANTOS trials).

Dr Genest sits on several advisory boards for pharmaceutical and biotechnology companies and is a reviewer for many scientific journals and granting agencies. He has published over 340 peer-reviewed manuscripts in journals such as Nature Genetics, Circulation, Circulation Research, New England Journal of Medicine, Journal of Biological Chemistry, European Heart Journal and the Lancet and has written 18 book chapters. His h-index is 57 (69 Scopus; citations: 17,423). For the past 24 years, he has participated in the elaboration of Canadian Cholesterol Guidelines. He currently leads FH Canada (www.FHCanada.net), a clinical network that aims to provide optimal treatment to patients with this disorder.

Dr Jacques Genest discloses: Grant and research support from the Canadian Institutes of Health Research and FH Canada (Chair). Consultancy fees from Amgen and Sanofi.

Prof. Kausik Ray

Imperial College London, London, UK

Kausik Ray is Professor of Public Health, Deputy Director of Imperial Clinical Trials Unit and Head of Commercial Trials within the Department of Public Health and Primary Care, School of Public Health at Imperial College London. He is a Consultant Cardiologist and Chief Clinical Officer and Head of Trials at Discover-NOW, as well as NIHR ARC (National Institute for Health Research Applied Research Collaborations) National Lead of Cardiovascular Disease (CVD).

Prof. Ray’s research interests have focused on the prevention of coronary disease with a focus on lipids, diabetes, biomarkers and risk prediction. He has an h-index of 81, an i10 of 205 and over 84,000 citations for his work. Key original contributions which have influenced European and American guidelines include demonstrating the early benefits of statin therapy post-acute coronary syndrome, the impact of more/less intensive glycaemic control on CVD and the risks/benefits of aspirin therapy in primary prevention. Currently Prof. Ray leads the European Atherosclerosis Society Familial Hypercholesterolaemia (EAS-FH) Studies Collaboration.

A Fellow of the American College of Cardiology, the European Society of Cardiology, the American Heart Association and the Royal College of Physicians, Prof. Ray is also a member of the British Cardiovascular Society and President-Elect of the European Atherosclerosis Society (EAS), also serving on the EAS Consensus panel and EAS Executive Committee. He has been the national lead investigator, principal investigator, and served on committees for several major medical trials, as well as international registries.

Prof. Kausik Ray discloses: Grant and research support from Amgen, Daiichi Sankyo, MSD, Pfizer, Regeneron Pharmaceuticals and Sanofi. Consultancy/Advisory board fees from AbbVie, Akcea Therapeutics, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cerenis Therapeutics, Eli Lilly and Company, Esperion Therapeutics, Ionis Pharmaceuticals, Kowa Pharmaceuticals, MedCo, MSD, NewAmsterdam Pharma, Novartis, Novo Nordisk, Pfizer, Regeneron Pharmaceuticals, Sanofi, Takeda and The Medicines Company. Speaker Bureau fees from Amgen, AstraZeneca, Boehringer Ingelheim, Cipla, Dr Reddy’s Laboratories Ltd., Novo Nordisk, Pfizer, Sanofi and Zuellig Pharma. Honorarium/Honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Kowa, Novo Nordisk, Pfizer and Sanofi. Stock options in Pemi31 Therapeutics, Inc.

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Question 1/4
What are the three primary statin medications used in clinical practice for lowering cholesterol levels?
Correct

Atorvastatin, rosuvastatin and simvastatin are the primary statins used in clinical practice for lowering cholesterol levels.1 There are currently seven statins approved by the FDA for lowering cholesterol levels (atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin).2

Abbreviations
FDA, US Food and Drug Administration.

References

  1. Grundy S, et al. J Am Coll Cardiol. 2019;73:3168–209.
  2. US Food and Drug Administration. Information by Drug Class – Statins. Available at: www.fda.gov/drugs/information-drug-class/statins (accessed November 2020).
Question 2/4
Complete the sentence: Treatment using a high-intensity statin typically lowers LDL-C levels by…

Abbreviations LDL-C, low-density lipoprotein cholesterol.
Correct

The intensity of statin therapy is divided into three categories: high-intensity, moderate-intensity, and low-intensity. High-intensity statin therapy typically lowers LDL-C levels by ≥50%, moderate-intensity statin therapy by 30–49%, and low-intensity statin therapy by <30%.

Abbreviations
LDL-C, low-density lipoprotein cholesterol.

Reference
Grundy S, et al. J Am Coll Cardiol. 2019;73:3168–209.

Question 3/4
Which lipid and lipoprotein analyses would you use in your daily practice to estimate the risk of ASCVD and guide therapeutic decision-making according to ESC/EAS guidelines?

Abbreviations ApoA, apolipoprotein A; ApoB, apolipoprotein B; ASCVD, atherosclerotic cardiovascular disease; ESC/EAS, European Society of Cardiology/European Atherosclerosis Society; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein (a); TC, total cholesterol; TG, triglyceride.
Correct

The 2019 ESC/EAS guidelines recommend the following lipid analyses for estimation of ASCVD risk:

  • Plasma TC and HDL-C should be used to estimate a person’s risk using SCORE
  • Plasma LDL-C should be measured to estimate the risk of ASCVD that can be modified with LDL-C-lowering therapies
  • Plasma TG should be assessed to identify people who may have a greater modifiable risk of ASCVD than is reflected by LDL-C
  • ApoB is used to further refine the estimate of ASCVD risk that is modifiable by lipid-lowering therapy

Abbreviations
ApoB, apolipoprotein B; ASCVD, atherosclerotic cardiovascular disease; ESC/EAS, European Society of Cardiology/European Atherosclerosis Society; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; SCORE, systematic coronary risk estimation; TC, total cholesterol; TG, triglyceride.

Reference
Mach F, et al. Eur Heart J. 2020;41:111–88.

Question 4/4
After 6 weeks of high-intensity atorvastatin plus ezetimibe therapy, your patient is still not reaching treatment goals and you decide to add a PCSK9 inhibitor to their treatment regimen. Your patient asks what new side effects to expect with a PCSK9 inhibitor. How would you advise your patient?

Abbreviations PCSK9, proprotein convertase subtilisin/kexin type 9.
Correct

PCSK9 inhibitors are injected subcutaneously, every other week or once a month, at different doses depending on the agent used.1 Injection-site reactions were infrequent in the recent PCSK9 clinical outcomes trials in patients receiving high-intensity statin therapy (FOURIER2 and ODYSSEY OUTCOMES3), but were more common in those receiving a PCSK9 inhibitor than those receiving a matching placebo as subcutaneous injection (FOURIER 2.1% versus 1.6% and ODYSSEY 3.8% versus 2.1%).

Abbreviations
PCSK9, proprotein convertase subtilisin/kexin type 9.

References

  1. Mach F, et al. Eur Heart J. 2020;41:111–88.
  2. Sabatine MS, et al; FOURIER Steering Committee and Investigators. N Engl J Med. 2017;376:1713–22.
  3. Schwartz GG, et al; ODYSSEY OUTCOMES Committees and Investigators. N Engl J Med. 2018;379:2097–107.
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