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31 août 2019 · Nor do the ESC/EAS Guidelines exempt health professionals from taking into full and careful consideration the 9 Management of dyslipidaemias in different clinical settings dyslipidemias through lifestyle modifications?

The content of these European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) Guidelines has been published for personal and

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31 août 2019 · 2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk☆ Authors/Task Force

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2019 ESC/EAS Guidelines for the management

of dyslipidaemias:lipid modification to reduce cardiovascular risk The Task Force for the management of dyslipidaemias of the

European Society of Cardiology (ESC) and European

Atherosclerosis Society (EAS)

Authors/Task Force Members: Franc¸ois Mach* (Chairperson) (Switzerland), Colin Baigent* (Chairperson) (United Kingdom), Alberico L. Catapano 1 (Chairperson) (Italy), Konstantinos C. Koskinas (Switzerland), Manuela Casula 1 (Italy), Lina Badimon (Spain), M. John Chapman 1 (France), Guy G. De Backer (Belgium), Victoria Delgado (Netherlands), Brian A. Ference (United Kingdom), Ian M. Graham (Ireland), Alison Halliday (United Kingdom), Ulf Landmesser (Germany), Borislava Mihaylova (United Kingdom), Terje R. Pedersen (Norway),

Gabriele Riccardi

1 (Italy), Dimitrios J. Richter (Greece), Marc S. Sabatine (United

States of America), Marja-Riitta Taskinen

1 (Finland), Lale Tokgozoglu 1 (Turkey),

Olov Wiklund

1 (Sweden) The three chairpersons contributed equally to the document.

*Corresponding authors: Franc¸ois Mach, Cardiology Department, Geneva University Hospital, 4 Gabrielle-Perret-Gentil, 1211 Geneva, Switzerland. Tel:þ41 223 727 192,

Fax:þ41 223 727 229, Email: francois.mach@hcuge.ch. Colin Baigent, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Roosevelt Drive,

Oxford OX3 7LF, United Kingdom. Tel:þ44 1865 743 741, Fax:þ44 1865 743 985, Email: colin.baigent@ndph.ox.ac.uk. Alberico L. Catapano, Department of Pharmacological

and Biomolecular Sciences, University of Milan, Via Balzaretti, 9, 20133 Milan, and Multimedica IRCCS, Milan, Italy. Tel:þ39 02 5031 8401, Fax:þ39 02 5031 8386,

Email: alberico.catapano@unimi.it.

ESC Committee for Practice Guidelines (CPG), National Cardiac Societies document reviewers and Author/Task Force Member affiliations: listed in the Appendix.

Representing the EAS.

ESC entities having participated in the development of this document:

Associations:Acute Cardiovascular Care Association (ACCA), Association of Cardiovascular Nursing & Allied Professions (ACNAP), European Association of Cardiovascular

Imaging (EACVI), European Association of Preventive Cardiology (EAPC), European Association of Percutaneous Cardiovascular Interventions (EAPCI).

Councils:Council for Cardiology Practice, Council on Hypertension, Council on Stroke.

Working Groups:Aorta and Peripheral Vascular Diseases, Atherosclerosis and Vascular Biology, Cardiovascular Pharmacotherapy, e-Cardiology, Thrombosis.

The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of

the ESC Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of awritten request to

Oxford University Press, the publisher of theEuropean Heart Journaland the party authorized to handle such permissions on behalf of the ESC (journals.permissions@oxfordjour-

nals.org).

Disclaimer. The ESC/EAS Guidelines represent the views of the ESC and EAS, and were produced after careful consideration of the scientific and medical knowledge,and the

evidence available at the time of their publication. The ESC and EAS is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the ESC/EAS

Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic

strategies. Health professionals are encouraged to take the ESC/EAS Guidelines fully into account when exercising their clinical judgment, as wellas in the determination and the

implementation of preventive, diagnostic, or therapeutic medical strategies; however, the ESC/EAS Guidelines do not override, in any way whatsoever, the individual responsibil-

ity of health professionals to make appropriate and accurate decisions in consideration of each patient"s health condition and in consultation withthat patient and, where appro-

priate and/or necessary, the patient"s caregiver. Nor do the ESC/EAS Guidelines exempt health professionals from taking into full and careful consideration the relevant official

updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient"s case in light of the scientifically accepted data pur-

suant to their respective ethical and professional obligations. It is also the health professional"s responsibility to verify the applicable rulesand regulations relating to drugs and

medical devices at the time of prescription.

For permissions please email: journals.permissions@oup.com.

European Heart Journal (2019)00,1?78

ESC/EAS GUIDELINES

doi:10.1093/eurheartj/ehz455Downloaded from https://academic.oup.com/eurheartj/advance-article-abstract/doi/10.1093/eurheartj/ehz455/5556353 by guest on 31 August 2019

Document Reviewers: Christian Mueller (ESC Review Coordinator) (Switzerland), Heinz Drexel (EAS Review Coordinator) (Austria), Victor Aboyans (France), Alberto Corsini 1 (Italy), Wolfram Doehner (Germany), Michel Farnier (France), Bruna Gigante (Sweden), Meral Kayikcioglu 1 (Turkey),

Goran Krstacic (Croatia), Ekaterini Lambrinou (Cyprus), Basil S. Lewis (Israel), Josep Masip (Spain),

Philippe Moulin

1 (France), Steffen Petersen (United Kingdom), Anna Sonia Petronio (Italy),

Massimo Francesco Piepoli (Italy), Xavier Pint

?o 1 (Spain), Lorenz Raber (Switzerland), Kausik K. Ray 1 (United Kingdom),?Zeljko Reiner 1 (Croatia), Walter F. Riesen (Switzerland), Marco Roffi (Switzerland), Jean-Paul Schmid (Switzerland), Evgeny Shlyakhto (Russian Federation), Iain A. Simpson (United

Kingdom), Erik Stroes

1 (Netherlands), Isabella Sudano (Switzerland), Alexandros D. Tselepis 1 (Greece),

Margus Viigimaa

1 (Estonia), Cecile Vindis (France), Alexander Vonbank (Austria), Michal Vrablik 1 (Czech

Republic), Mislav Vrsalovic (Croatia), Jose´ Luis Zamorano Gomez (Spain), Jean-Philippe Collet (ESC CPG

Supervisor) (France)

The disclosure forms of all experts involved in the development of these Guidelines are available on the

ESC websitewww.escardio.org/guidelines

For the Supplementary Data which include background information and detailed discussion of the data

that have provided the basis for the Guidelines seehttps://academic.oup.com/eurheartj/article-lookup/doi/

Keywords

Guidelines

dyslipidaemias cholesterol triglycerides low-density lipoproteins high-density lipopro- teins apolipoprotein B lipoprotein(a) lipoprotein remnants total cardiovascular risk treatment (lifestyle) treatment (drugs) treatment (adherence) very low-density lipoproteins familial hypercholesterolaemia

Abbreviationsandacronyms ........................................ 4

1Preamble......................................................... 6

2Introduction...................................................... 8

2.1Whatisnewinthe2019Guidelines? .......................... 8

3Whatiscardiovasculardiseaseprevention? ........................ 8

3.1Definitionandrationale ....................................... 8

3.2 Developmentofthe JointTaskForceGuidelinesforthe

managementofdyslipidaemias.................................... 8

4Totalcardiovascularrisk .......................................... 8

4.1Totalcardiovascularriskestimation ........................... 8

4.1.1 Rationaleforassessingtotal cardiovasculardisease risk ... . 11

4.1.2 Howtousethe riskestimationcharts . .. ... .. ... ... .. ... . 14

4.2Risklevels ................................................... 15

4.2.1 Role ofnon-invasive cardiovascularimaging

diseaserisk ................................................... 16

4.2.2Risk-basedinterventionstrategies ........................ 17

5Lipidsandlipoproteins ........................................... 17

5.1Biologicalroleoflipidsandlipoproteins....................... 17

5.2 Role oflipidsandlipoproteinsinthe pathophysiology of

atherosclerosis ................................................. 17

5.3 Evidence forthe causal effectsoflipidsandlipoproteinson

theriskofatheroscleroticcardiovasculardisease ... .. ... ... .. ... . 18

5.3.1 Low-densitylipoproteincholesterolandrisk of

atherosclerosis ............................................... 18

5.3.2 Triglyceride-richlipoproteinsandrisk ofatherosclerosis . . 18

5.3.3 High-densitylipoprotein cholesterolandrisk of

atherosclerosis ............................................... 195.3.4 Lipoprotein(a) andriskofatherosclerosis ... ... .. ... .. ... 19

5.4Laboratorymeasurementoflipidsandlipoproteins . .. ... .. ... 19

5.4.1Lipoproteinmeasurement ............................... 19

5.4.2Lipidmeasurements ..................................... 20

5.4.3Fastingornon-fasting? ................................... 20

estimateriskofatheroscleroticcardiovasculardisease .. .. ... .. ... 20

6Treatmenttargetsandgoals...................................... 21

7Lifestylemodificationsto improve theplasmalipidprofile .. ... .. ... 22

7.1Influence oflifestyleontotalcholesterolandlow-density

lipoproteincholesterollevels .................................... 24

7.2Influenceoflifestyleontriglyceridelevels ..................... 24

7.3Influence oflifestyleonhigh-density lipoprotein cholesterol

levels ........................................................... 25

7.4Lifestyle recommendationsto improve theplasmalipid

profile .......................................................... 25

7.4.1Bodyweightandphysicalactivity ......................... 25

7.4.2Dietaryfat .............................................. 25

7.4.3Dietarycarbohydrateandfibre .......................... 26

7.4.4Alcohol ................................................. 26

7.4.5Smoking ................................................ 26

treatmentofdyslipidaemias ..................................... 26

7.5.1Phytosterols ............................................ 26

7.5.2Monacolinandredyeastrice............................. 26

7.5.3Dietaryfibre ............................................ 27

7.5.4Soy ..................................................... 27

7.5.5Policosanolandberberine ............................... 27

7.5.6n-3unsaturatedfattyacids ............................... 27

2ESC/EAS GuidelinesDownloaded from https://academic.oup.com/eurheartj/advance-article-abstract/doi/10.1093/eurheartj/ehz455/5556353 by guest on 31 August 2019

8Drugsfortreatmentofdyslipidaemias ............................ 27

8.1Statins ...................................................... 27

8.1.1Mechanismofaction .................................... 27

8.1.2Effectsonlipids.......................................... 27

8.1.2.1Low-densitylipoproteincholesterol...................... 27

8.1.2.2Triglycerides......................................... 27

8.1.2.3High-densitylipoproteincholesterol..................... 27

8.1.2.4Lipoprotein(a)........................................ 27

8.1.3Othereffectsofstatins .................................. 28

8.1.3.1Effectoncardiovascularmorbidityandmortality.......... 28

8.1.4 Adverseeffectsandinteractionsofstatins .. .. ... ... .. ... . 28

8.1.4.1Adverseeffectsonmuscle............................. 28

8.1.4.2Adverseeffectsontheliver............................. 29

8.1.4.3Increasedriskofnew-onsetdiabetesmellitus............. 29

8.1.4.4Increasedriskofhaemorrhagicstroke................... 29

8.1.4.5Adverseeffectsonkidneyfunction...................... 29

8.1.4.6Interactions.......................................... 29

8.2Cholesterolabsorptioninhibitors ............................ 30

8.2.1Mechanismofaction .................................... 30

8.2.2Effectsonlipids.......................................... 30

8.2.3 Effect oncardiovascularmorbidityandmortality . ... .. ... . 30

8.2.4Adverseeffectsandinteractions ......................... 30

8.3Bileacidsequestrants ........................................ 30

8.3.1Mechanismofaction .................................... 30

8.3.2Effectsonlipids.......................................... 30

8.3.3 Effect oncardiovascularmorbidityandmortality . ... .. ... . 30

8.3.4Adverseeffectsandinteractions ......................... 31

8.4 Proprotein convertasesubtilisin/kexin type9 inhibitors .. .. ... . 31

8.4.1Mechanismofaction .................................... 31

8.4.2Effectsonlipids.......................................... 31

8.4.2.1Low-densitylipoproteincholesterol...................... 31

8.4.2.2Triglyceridesandhigh-densitylipoproteincholesterol...... 31

8.4.2.3Lipoprotein(a)........................................ 31

8.4.3 Effect oncardiovascularmorbidityandmortality . ... .. ... . 31

8.4.4Adverseeffectsandinteractions ......................... 32

8.5Lomitapide .................................................. 32

8.6Mipomersen ................................................ 32

8.7Fibrates ..................................................... 32

8.7.1Mechanismofaction .................................... 32

8.7.2Effectsonlipids.......................................... 32

8.7.3 Effect oncardiovascularmorbidityandmortality . ... .. ... . 33

8.7.4Adverseeffectsandinteractions ......................... 33

8.8n-3fattyacids ............................................... 33

8.8.1Mechanismofaction .................................... 33

8.8.2Effectsonlipids.......................................... 33

8.8.3 Effect oncardiovascularmorbidityandmortality . ... .. ... . 33

8.8.4Safetyandinteractions................................... 34

8.9Nicotinicacid ............................................... 34

8.10Cholesteryl estertransferprotein inhibitors ... .. ... ... .. ... . 34

8.11Futureperspectives ........................................ 34

8.11.1Newapproachestoreducelow-density lipoprotein

cholesterol................................................... 34 lipoproteinsandtheirremnants ............................... 34

8.11.3Newapproachestoincrease high-densitylipoprotein

cholesterol................................................... 35

8.11.4Newapproachestoreducelipoprotein(a) levels ... .. ... . 358.12Strategiestocontrolplasmacholesterol..................... 35

8.13Strategiestocontrolplasmatriglycerides .................... 35

9Management ofdyslipidaemiasin differentclinical settings . ... .. ... 38

9.1Familialdyslipidaemias ....................................... 38

9.1.1Familialcombinedhyperlipidaemia ....................... 38

9.1.2Familialhypercholesterolaemia .......................... 38

9.1.2.1Heterozygousfamilialhypercholesterolaemia............ 38

9.1.2.2Homozygousfamilialhypercholesterolaemia............ 41

9.1.2.3Familialhypercholesterolaemiainchildren............... 41

9.1.3 Familialdysbetalipoproteinaemia .. .. ... .. ... ... .. ... .. ... 41

9.1.4 Geneticcausesofhypertriglyceridaemia .. ... ... .. ... .. ... 41

9.1.4.1 Action to prevent acute pancreatitis in severe

hypertriglyceridaemia........................................ 41

9.1.5 Othergeneticdisordersoflipoproteinmetabolism .. .. ... 42

9.2Women .................................................... 42

9.2.1 Effectsofstatinsinprimary andsecondary prevention .. ... 42

9.2.2Non-statinlipid-loweringdrugs .......................... 42

9.2.3Hormonetherapy ....................................... 42

9.3Olderpeople................................................ 42

9.3.1 Effectsofstatinsinprimary andsecondary prevention .. ... 43

9.3.2Adverseeffects,interactions,andadherence.............. 43

9.4Diabetesandmetabolicsyndrome ........................... 43

9.4.1 Specific featuresofdyslipidaemiain insulin resistance

andtype2diabetes ........................................... 43

9.4.2Evidenceforlipid-loweringtherapy ...................... 44

9.4.2.1Low-densitylipoprotein cholesterol...................... 44

9.4.2.1Triglyceridesandhigh-densitylipoproteincholesterol...... 44

9.4.3Type1diabetes ......................................... 45

9.4.4 Managementofdyslipidaemiaforpregnantwomen

withdiabetes ................................................. 45

9.5Patientswith acutecoronary syndromesandpatients

undergoingpercutaneouscoronaryintervention ................. 46

9.5.1 Lipid-loweringtherapy in patientswithacute

coronarysyndromes ......................................... 46

9.5.1.1 Statins.............................................. 46

9.5.1.2 Ezetimibe........................................... 46

9.5.1.3 Proprotein convertase subtilisin/kexin type 9 inhibitors..... 46

9.5.1.4n-3 polyunsaturatedfattyacids......................... 47

9.5.1.5Cholesterylestertransferproteininhibitors............... 47

9.5.2 Lipid-loweringtherapy in patientsundergoing

percutaneouscoronaryintervention .......................... 47

9.6Stroke ...................................................... 48

9.7Heartfailureandvalvulardiseases ............................ 48

9.7.1 Prevention ofincidentheartfailureincoronaryartery

diseasepatients .............................................. 48

9.7.2Chronicheartfailure .................................... 48

9.7.3Valvularheartdiseases................................... 48

9.8Chronickidneydisease ...................................... 49

9.8.1 Lipoproteinprofileinchronic kidneydisease . ... .. ... .. ... 49

9.8.2 Evidenceforrisk reductionthrough statin-based

therapyinpatientswithchronickidneydisease................. 49

9.8.3 Safetyoflipidmanagementin patientswithchronic

kidneydisease ................................................ 49

9.9Transplantation ............................................. 50

9.10Peripheralarterialdisease................................... 50

9.10.1Lowerextremityarterialdisease ........................ 50

9.10.2Carotidarterydisease .................................. 51

ESC/EAS Guidelines3Downloaded from https://academic.oup.com/eurheartj/advance-article-abstract/doi/10.1093/eurheartj/ehz455/5556353 by guest on 31 August 2019

[PDF] [PDF] 2019 ESC/EAS Guidelines for the management of dyslipidaemias