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`
`European Heart Journal (2020) 41, 255323
`doi:10.1093/eurheartj/ehz486
`
`ESC GUIDELINES
`
`2019 ESC Guidelines on diabetes, pre-diabetes,
`and cardiovascular diseases developed in
`collaboration with the EASD
`
`The Task Force for diabetes, pre-diabetes, and cardiovascular
`diseases of the European Society of Cardiology (ESC) and the
`European Association for the Study of Diabetes (EASD)
`
`Authors/Task Force Members: Francesco Cosentino* (ESC Chairperson) (Sweden),
`Peter J. Grant* (EASD Chairperson) (United Kingdom), Victor Aboyans (France),
`Clifford J. Bailey1 (United Kingdom), Antonio Ceriello1 (Italy),
`Victoria Delgado (Netherlands), Massimo Federici1 (Italy), Gerasimos Filippatos
`(Greece), Diederick E. Grobbee (Netherlands), Tina Birgitte Hansen (Denmark),
`Heikki V. Huikuri (Finland), Isabelle Johansson (Sweden), Peter Ju¨ ni (Canada),
`Maddalena Lettino (Italy), Nikolaus Marx (Germany), Linda G. Mellbin (Sweden),
`Carl J. €Ostgren (Sweden), Bianca Rocca (Italy), Marco Roffi (Switzerland),
`Naveed Sattar1 (United Kingdom), Petar M. Seferovic (Serbia), Miguel Sousa-Uva
`(Portugal), Paul Valensi (France), and David C. Wheeler1 (United Kingdom)
`
`*Corresponding authors: Francesco Cosentino, Cardiology Unit, Department of Medicine Solna, Karolinska Institute and Karolinska University Hospital, Solna, 171 76 Stockholm,
`Sweden. Tel: þ46 8 517 72 245; Fax: þ46 8 34 49 64, Email: francesco.cosentino@ki.se. Peter J. Grant, Leeds Institute of Cardiovascular and Metabolic Medicine, University of
`Leeds/Leeds Teaching Hospitals NHS Trust, LIGHT Laboratories, Clarendon Way, Leeds LS2 9JT, UK. Tel: þ44 44 113 343 7721, Email: p.j.grant@leeds.ac.uk.
`Authors/Task Force Member Affiliations: listed in the Appendix.
`
`ESC Committee for Practice Guidelines (CPG) and National Cardiac Societies document reviewers: listed in the Appendix.
`
`1Representing the EASD.
`
`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), European Heart Rhythm
`Association (EHRA), Heart Failure Association (HFA).
`
`Councils: Council on Cardiovascular Primary Care, Council on Hypertension.
`
`Working Groups: Aorta and Peripheral Vascular Diseases, Cardiovascular Surgery, Thrombosis.
`
`The content of these ESC Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of the Guidelines may be translated
`or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to Oxford University Press, the publisher
`of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC (journals.permissions@oxfordjournals.org).
`
`Disclaimer: The Guidelines represent the views of the ESC 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 EASD are not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the 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 profes-
`sionals are encouraged to take the Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive,
`diagnostic, or therapeutic medical strategies; however, the Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appro-
`priate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s care-
`giver. Nor do the 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 pursuant to their respective ethical and professional obli-
`gations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.
`
`VC The European Society of Cardiology 2019. All rights reserved. For permissions please email: journals.permissions@oup.com.
`
`Novo Nordisk Exhibit 2090
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00001
`
`

`

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`256
`
`ESC Guidelines
`
`Document Reviewers: Massimo Francesco Piepoli (ESC Review Coordinator) (Italy), Ka˚ re I. Birkeland1
`(EASD Review Coordinator) (Norway), Stamatis Adamopoulos (Greece), Ramzi Ajjan (United Kingdom),
`Angelo Avogaro (Italy), Colin Baigent (United Kingdom), Marianne Brodmann (Austria), He´ ctor Bueno
`(Spain), Claudio Ceconi (Italy), Ovidiu Chioncel (Romania), Andrew Coats (United Kingdom), Jean-Philippe
`Collet (France), Peter Collins (United Kingdom), Bernard Cosyns (Belgium), Carlo Di Mario (Italy), Miles
`Fisher1 (United Kingdom), Donna Fitzsimons (United Kingdom), Sigrun Halvorsen (Norway), Dominique
`Hansen (Belgium), Arno Hoes (Netherlands), Richard I. G. Holt1 (United Kingdom), Philip Home1 (United
`Kingdom), Hugo A. Katus (Germany), Kamlesh Khunti (United Kingdom), Michel Komajda (France),
`Ekaterini Lambrinou (Cyprus), Ulf Landmesser (Germany), Basil S. Lewis (Israel), Cecilia Linde (Sweden),
`Roberto Lorusso (Netherlands), Franc¸ois Mach (Switzerland), Christian Mueller (Switzerland), Franz-Josef
`Neumann (Germany), Frederik Persson1 (Denmark), Steffen E. Petersen (United Kingdom), Anna Sonia
`Petronio (Italy), Dimitrios J. Richter (Greece), Giuseppe M. C. Rosano (Italy/United Kingdom), Peter
`Rossing1 (Denmark), Lars Ryde´ n (Sweden), Evgeny Shlyakhto (Russian Federation), Iain A. Simpson
`(United Kingdom), Rhian M. Touyz (United Kingdom), William Wijns (Ireland), Matthias Wilhelm
`(Switzerland), Bryan Williams (United Kingdom)
`The disclosure forms of all experts involved in the development of these Guidelines are available on the
`ESC website www.escardio.org/guidelines
`
`Click here to access the corresponding chapter in ESC CardioMed - Section 19 Diabetes mellitus and
`metabolic syndrome
`
`Online publish-ahead-of-print 31 August 2019
`
`...................................................................................................................................................................................................
`Guidelines • diabetes mellitus • impaired glucose tolerance • cardiovascular diseases • epidemiology • risk
`Keywords
`factors • prevention • cardiovascular risk assessment • patient management • pharmacological treatment •
`revascularization • patient-centred care
`
`Table of contents
`
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258
`Abbreviations and acronyms
`1 Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 260
`2 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262
`3 What is new in the 2019 Guidelines?
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
`4 Diagnosis of diabetes and pre-diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . 265
`5 Cardiovascular risk assessment in patients with diabetes
`and pre-diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 266
`5.1 Diabetes, pre-diabetes, and cardiovascular risk . . . . . . . . . . . . . . 266
`5.2 Stratification of cardiovascular risk in individuals with
`diabetes
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
`5.3 Stratification of cardiovascular risk in individuals with
`pre-diabetes
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
`5.4 Clinical assessment of cardiovascular damage . . . . . . . . . . . . . . . 267
`5.4.1 Biomarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
`5.4.2 Electrocardiography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268
`5.4.3 Imaging techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268
`6 Prevention of cardiovascular disease in patients with diabetes
`and pre-diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
`6.1 Lifestyle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
`6.1.1 Diet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
`6.1.1.1 Carbohydrate
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
`6.1.1.2 Fats
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
`6.1.1.3 Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
`
`............................................................................
`
`6.1.1.4 Vegetables, legumes, fruits, and wholegrain cereals . . . . . . 271
`6.1.1.5 Alcohol consumption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
`6.1.1.6 Coffee and tea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
`6.1.1.7 Vitamins and macronutrients
`. . . . . . . . . . . . . . . . . . . . . . . . . 271
`6.1.2 Physical activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272
`6.1.3 Smoking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272
`6.2 Glucose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272
`6.2.1 Glycaemic targets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272
`6.2.1.1 Additional glucose targets
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . 272
`6.2.2 Glucose-lowering agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
`6.2.3 Special considerations
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
`6.2.3.1 Hypoglycaemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
`6.2.3.2 Glucose monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
`6.3 Blood pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274
`6.3.1 Treatment targets
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274
`6.3.2 Management of blood pressure lowering
`. . . . . . . . . . . . . . . 274
`6.3.2.1 Effects of lifestyle intervention and weight loss
`. . . . . . . . . . 274
`6.3.2.2 Pharmacological treatments . . . . . . . . . . . . . . . . . . . . . . . . . . 274
`6.3.2.3 Blood pressure changes with glucose-lowering
`treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274
`6.4 Lipids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
`6.4.1 Lipid-lowering agents
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
`6.4.1.1 Statins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
`6.4.1.2 Ezetimibe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276
`6.4.1.3 Proprotein convertase subtilisin/kexin type 9 . . . . . . . . . . . . 276
`
`Novo Nordisk Exhibit 2090
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00002
`
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`ESC Guidelines
`
`257
`
`6.4.1.4 Fibrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276
`6.5 Platelets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
`6.5.1 Aspirin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
`6.5.1.1 Primary prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278
`6.5.1.2 Secondary prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278
`6.6 Multifactorial approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278
`6.6.1 Principles of multifactorial management . . . . . . . . . . . . . . . . . 278
`7 Management of coronary artery disease . . . . . . . . . . . . . . . . . . . . . . . . . 280
`7.1 Medical treatment
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
`7.1.1 Effects of intensified glucose control
`. . . . . . . . . . . . . . . . . . . . 280
`7.1.1.1 UKPDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
`7.1.1.2 ACCORD, ADVANCE, and VADT . . . . . . . . . . . . . . . . . . . . . 280
`7.1.1.3 DIGAMI 1 and 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
`7.1.2 Glucose-lowering agents: new evidence from
`cardiovascular outcome trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
`7.1.2.1 Established oral glucose-lowering drugs . . . . . . . . . . . . . . . . 281
`7.1.2.2 Newer oral glucose-lowering drugs
`. . . . . . . . . . . . . . . . . . . . 281
`7.1.2.3 Implications of recent cardiovascular outcome trials
`. . . . . 283
`7.1.3 Specific cardiovascular therapies . . . . . . . . . . . . . . . . . . . . . . . . 286
`7.1.3.1 Beta-blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286
`7.1.3.2 Blockers of the reninangiotensinaldosterone system . 286
`7.1.3.3 Lipid-lowering drugs
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286
`7.1.3.4 Nitrates and calcium channel blockers . . . . . . . . . . . . . . . . . 286
`7.1.3.5 Other anti-ischaemic drugs
`. . . . . . . . . . . . . . . . . . . . . . . . . . 286
`7.1.3.6 Antiplatelet and antithrombotic drugs (see section 6.5)
`. . 287
`7.2 Revascularization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288
`7.2.1 Percutaneous coronary intervention vs. coronary artery
`bypass graft surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288
`7.2.2 Adjunctive pharmacotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
`8 Heart failure and diabetes
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290
`8.1 Prognostic implications of diabetes mellitus in heart failure . . . 291
`8.2 Mechanisms of left ventricular dysfunction in diabetes
`mellitus
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
`8.3 Phenotypes of left ventricular dysfunction in diabetes
`mellitus
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
`8.4 Treatment of heart failure in diabetes mellitus . . . . . . . . . . . . . . . 292
`8.4.1 Renin-angiotensin-aldosterone system and a
`neprilysin inhibitors
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
`8.4.2 Beta-blockers
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
`8.4.3 Ivabradine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
`8.4.4 Digoxin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
`8.4.5 Diuretics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
`8.4.6 Device therapy and surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
`8.5 Effect of oral glucose-lowering agents on heart failure . . . . . . . . 292
`8.5.1 Metformin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
`8.5.2 Sulfonylureas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
`8.5.3 Thiazolidinediones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
`8.5.4 Dipeptidyl peptidase-4 inhibitors
`. . . . . . . . . . . . . . . . . . . . . . . 292
`8.5.5 Glucagon-like peptide-1 receptor agonists . . . . . . . . . . . . . . 292
`8.5.6 Sodium-glucose co-transporter 2 inhibitors . . . . . . . . . . . . . 292
`9 Arrhythmias: atrial fibrillation, ventricular arrhythmias,
`and sudden cardiac death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294
`9.1 Atrial fibrillation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294
`9.1.1 Diabetes and risk of stroke in atrial fibrillation . . . . . . . . . . . 294
`9.2 Ventricular arrhythmias and sudden cardiac death . . . . . . . . . . . 294
`9.2.1 Ventricular premature beats and paroxysmal ventricular
`tachycardia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294
`
`.............................................................................................................................................................................
`
`9.2.2 Sustained ventricular arrhythmias . . . . . . . . . . . . . . . . . . . . . . . 294
`9.2.3 Sudden cardiac death in diabetes
`. . . . . . . . . . . . . . . . . . . . . . . 294
`10 Aortic and peripheral arterial diseases
`. . . . . . . . . . . . . . . . . . . . . . . . . 295
`10.1 Aortic disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295
`10.2 Lower extremity arterial disease . . . . . . . . . . . . . . . . . . . . . . . . . . 295
`10.2.1 Epidemiology and natural history . . . . . . . . . . . . . . . . . . . . . . 296
`10.2.2 Screening and diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 296
`10.2.3 Management of lower extremity artery disease in
`diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297
`10.3 Carotid artery disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297
`11 Chronic kidney disease in diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299
`11.1 Management
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299
`11.1.1 Glycaemic control
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299
`11.1.2 New approaches to renoprotection . . . . . . . . . . . . . . . . . . . 299
`12 Patient-centred care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300
`12.1 General aspects
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300
`13 ‘What to do’ and ‘what not to do’ messages from the Guidelines . . 302
`14 Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
`15 References
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306
`
`Recommendations
`
`Recommendations for the diagnosis of disorders of glucose
`metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 266
`Recommendations for the use of laboratory, electrocardiogram,
`and imaging testing for cardiovascular risk assessment in
`asymptomatic patients with diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 270
`Recommendations for lifestyle modifications for patients with
`diabetes mellitus and pre-diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272
`Recommendations for glycaemic control in individuals with
`diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
`Recommendations for the management of blood pressure in
`patients with diabetes and pre-diabetes
`. . . . . . . . . . . . . . . . . . . . . . . . . . . 275
`Recommendations for the management of dyslipidaemia with
`lipid-lowering drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
`Recommendations for the use of antiplatelet therapy in primary
`prevention in patients with diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278
`Recommendations for multifactorial management of patients
`with diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
`Recommendations for glucose-lowering treatment for patients
`with diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286
`Recommendations for the management of patients with diabetes
`and acute or chronic coronary syndromes
`. . . . . . . . . . . . . . . . . . . . . . . . 287
`Recommendations for coronary revascularization in patients
`with diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
`Recommendations for the type of revascularization in patients
`with diabetes with stable coronary artery disease, suitable
`coronary anatomy for both procedures, and low predicted
`surgical mortality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290
`Recommendations for the treatment of heart failure in patients
`with diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
`Recommendations for the treatment of patients with type 2
`diabetes to reduce heart failure risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
`Recommendations for the management of arrhythmias in patients
`with diabetes
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295
`Recommendations for the diagnosis and management of peripheral
`artery disease in patients with diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298
`
`Novo Nordisk Exhibit 2090
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00003
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`258
`
`ESC Guidelines
`
`Recommendations for the prevention and management of chronic
`kidney disease in patients with diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300
`Recommendations for patient-centred care of individuals with
`diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
`
`List of tables
`
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
`Table 1 Classes of recommendations
`Table 2 Levels of evidence .
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
`Table 3 What is new in the 2019 Guidelines?
`. . . . . . . . . . . . . . . . . . . . . . 263
`Table 4 New recommendations in the 2019 Guidelines
`. . . . . . . . . . . 264
`Table 5 Revised concepts in the 2019 Guidelines . . . . . . . . . . . . . . . . . . 265
`Table 6 Diagnostic criteria for diabetes mellitus and pre-diabetes
`according to the 2006/2011 World Health Organization and
`2019 American Diabetes Association recommendations . . . . . . . . . . . 266
`Table 7 Cardiovascular risk categories in patients with diabetes
`. . . . 268
`Table 8 Overview of randomized controlled trials . . . . . . . . . . . . . . . . . 269
`Table 9 Summary of treatment targets for the management of
`patients with diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
`Table 10 Patient characteristics of cardiovascular safety studies
`with glucose-lowering agents
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284
`Table 11 Heart failure phenotypes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
`Table 12 Assessment of the risk of amputation: the Wound,
`Ischaemia, and foot Infection classification . . . . . . . . . . . . . . . . . . . . . . . . . 297
`Table 13 Chronic kidney disease classification by estimated
`glomerular filtration rate and albuminuria .
`. . . . . . . . . . . . . . . . . . . . . . . . . 299
`
`List of figures
`
`Figure 1 Hazard ratios for vascular outcomes in people with vs.
`without diabetes mellitus at baseline, based on analyses of
`530 083 patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
`Figure 2 Hazard ratios for coronary heart disease by clinically
`defined categories of baseline fasting blood glucose
`concentration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268
`Figure 3 Treatment algorithm in patients with type 2 diabetes
`mellitus and atherosclerotic cardiovascular disease, or high/very
`high CV risk.
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285
`Figure 4 Recommendations for coronary revascularization.
`. . . . . . . . 291
`Figure 5 Screening for lower extremity artery disease in patients
`with diabetes mellitus.
`. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 296
`
`Abbreviations and acronyms
`
`2hPG
`ABI
`ABPM
`ACCORD
`
`ACE
`ACEI
`ACS
`ADA
`ADVANCE
`
`2 h plasma glucose
`Anklebrachial index
`Ambulatory blood pressure monitoring
`Action to Control Cardiovascular Risk in
`Diabetes
`Acarbose Cardiovascular Evaluation
`Angiotensin-converting enzyme inhibitor
`Acute coronary syndrome
`American Diabetes Association
`Action in Diabetes and Vascular Disease:
`Preterax and Diamicron MR Controlled
`Evaluation
`
`.........................................................................................................................................................................
`
`ADDITION
`
`ADOPT
`AF
`ARB
`ART
`ASCEND
`
`BARI 2D
`
`BEST
`
`b.i.d.
`BIMA
`BMS
`BP
`b.p.m.
`CABG
`CAC
`CAD
`CANVAS
`
`CARDia
`
`Anglo-Danish-Dutch Study of Intensive
`Treatment In People with Screen Detected
`Diabetes in Primary Care
`A Diabetes Outcome Progression Trial
`Atrial fibrillation
`Angiotensin receptor blocker
`Arterial Revascularization Trial
`A Study of Cardiovascular Events iN
`Diabetes
`Atherosclerotic cardiovascular disease
`ASCVD
`ATLAS-ACS TIMI 51 Anti-Xa Therapy to Lower cardiovascular
`events in Addition to Standard therapy in
`subjects with Acute Coronary Syndromes -
`Thrombolysis In Myocardial Infarction 51
`Bypass Angioplasty Revascularization
`Investigation 2 Diabetes
`Randomized Comparison of Coronary
`Artery Bypass Surgery and Everolimus-
`Eluting Stent Implantation in the Treatment
`of Patients with Multivessel Coronary
`Artery Disease
`Twice a day (bis in die)
`Bilateral internal mammary artery
`Bare-metal stent
`Blood pressure
`Beats per minute
`Coronary artery bypass graft
`Coronary artery calcium
`Coronary artery disease
`Canagliflozin Cardiovascular Assessment
`Study
`Coronary Artery Revascularization in
`Diabetes
`Cardiovascular and Renal Microvascular
`Outcome Study With Linagliptin in Patients
`With Type 2 Diabetes Mellitus
`Cardiovascular Outcome Study of
`Linagliptin Versus Glimepiride in Patients
`With Type 2 Diabetes
`Chronic coronary syndrome
`Cardiac event
`Congestive heart failure, Hypertension,
`Age >_75 years (Doubled), Diabetes
`mellitus, Stroke or transient ischaemic
`attack (Doubled), Vascular disease, Age
`6574 years, Sex category
`Clopidogrel for High Atherothrombotic
`Risk and Ischemic Stabilization,
`Management and Avoidance
`Candesartan in Heart Failure Assessment
`of Reduction in Mortality and Morbidity
`Coronary heart disease
`Confidence interval
`Chronic kidney disease
`Chronic limb-threatening ischaemia
`
`CARMELINA
`
`CAROLINA
`
`CCS
`CE
`CHA2DS2-VASc
`
`CHARISMA
`
`CHARM
`
`CHD
`CI
`CKD
`CLTI
`
`Novo Nordisk Exhibit 2090
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00004
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`259
`
`Evaluation of XIENCE versus Coronary
`Artery Bypass Surgery for Effectiveness of
`Left Main Revascularization trial
`Examination of Cardiovascular Outcomes
`with Alogliptin versus Standard of Care
`Exenatide Study of Cardiovascular Event
`Lowering
`Screening For Asymptomatic Obstructive
`Coronary Artery Disease Among High-
`Risk Diabetic Patients Using CT
`Angiography, Following Core 64
`Fenofibrate Intervention and Event
`Lowering in Diabetes
`Further Cardiovascular Outcomes
`Research with PCSK9 Inhibition in Subjects
`with Elevated Risk
`Fasting plasma glucose
`Future Revascularization Evaluation in
`Patients with Diabetes Mellitus
`Glucose Abnormalities in Patients with
`Myocardial Infarction
`Glucagon-like peptide-1 receptor agonist
`Albiglutide and cardiovascular outcomes in
`patients with type 2 diabetes and
`cardiovascular disease
`Hypertension, Abnormal renal/liver
`function, Stroke, Bleeding history or
`predisposition, Labile international
`normalized ratio, Elderly (>65 years),
`Drugs/alcohol concomitantly
`Haemoglobin A1c
`Hyperglycemia and Its Effect After Acute
`Myocardial Infarction on Cardiovascular
`Outcomes in Patients With Type 2
`Diabetes Mellitus
`High-density lipoprotein cholesterol
`Heart failure
`Heart failure with mid-range ejection
`fraction
`Heart failure with preserved ejection
`fraction
`Heart failure with reduced ejection
`fraction
`Hazard ratio
`High-sensitivity cardiac troponin T
`Invasive coronary angiography
`Implantable cardioverter defibrillator
`Impaired fasting glycaemia
`Impaired glucose tolerance
`Improved Reduction of Outcomes: Vytorin
`Efficacy International Trial
`Japan Diabetes Optimal Integrated
`Treatment Study for 3 Major Risk Factors
`of Cardiovascular Diseases
`Kidney Disease: Improving Global
`Outcomes
`
`ESC Guidelines
`
`COMPASS
`
`CPG
`CREDENCE
`
`CREST
`
`CRT
`CRT-D
`
`CT
`CTCA
`
`CV
`CVD
`CVOT
`CVRF
`DADDY-D
`
`DAPT
`DBP
`DCCT
`DECLARE-
`TIMI 58
`
`DES
`DEVOTE
`
`DIAD
`
`DIGAMI
`
`DiRECT
`DM
`DPP4
`DYNAMIT
`
`EACTS
`
`EAS
`EASD
`
`ECG
`EDIC
`
`EET
`eGFR
`ELIXA
`
`EMPA-REG
`OUTCOME
`
`ESC
`
`Cardiovascular Outcomes for People
`Using Anticoagulation Strategies
`Committee for Practice Guidelines
`Canagliflozin and Renal Events in Diabetes
`with Established Nephropathy Clinical
`Evaluation
`Carotid Revascularization Endarterectomy
`versus Stenting Trial
`Cardiac resynchronization therapy
`Cardiac resynchronization therapy with an
`implantable defibrillator
`Computed tomography
`Computed tomography coronary
`angiography
`Cardiovascular
`Cardiovascular disease
`Cardiovascular outcome trial
`Cardiovascular risk factor
`Does coronary Atherosclerosis Deserve
`to be Diagnosed earlY in Diabetic patients?
`Dual antiplatelet therapy
`Diastolic blood pressure
`Diabetes Control and Complications Trial
`Dapagliflozin Effect on Cardiovascular
`Events-Thrombolysis In Myocardial
`Infarction 58 trial
`Drug-eluting stent
`Trial Comparing Cardiovascular Safety of
`Insulin Degludec versus Insulin Glargine in
`Patients with Type 2 Diabetes at High Risk
`of cardiovascular Events
`Detection of Ischaemia in Asymptomatic
`Diabetics
`Diabetes Mellitus Insulin-Glucose Infusion
`in Acute Myocardial Infarction
`Diabetes Remission Clinical Trial
`Diabetes mellitus
`Dipeptidyl peptidase-4
`Do You Need to Assess Myocardial
`Ischemia in Type 2 Diabetes
`European Association for Cardio-Thoracic
`Surgery
`European Atherosclerosis Society
`European Association for the Study of
`Diabetes
`Electrocardiogram
`Epidemiology of Diabetes Interventions
`and Complications
`Exercise electrocardiogram test
`Estimated glomerular filtration rate
`Evaluation of Lixisenatide in Acute
`Coronary Syndrome
`Empagliflozin Cardiovascular Outcome
`Event Trial in Type 2 Diabetes Mellitus
`PatientsRemoving Excess Glucose
`European Society of Cardiology
`
`EXCEL
`
`EXAMINE
`
`EXSCEL
`
`FACTOR-64
`
`FIELD
`
`FOURIER
`
`FPG
`FREEDOM
`
`GAMI
`
`GLP1-RA
`Harmony
`Outcomes
`
`HAS-BLED
`
`HbA1c
`HEART2D
`
`HDL-C
`HF
`HFmrEF
`
`HFpEF
`
`HFrEF
`
`HR
`hsTnT
`ICA
`ICD
`IFG
`IGT
`IMPROVE-IT
`
`J-DOIT3
`
`KDIGO
`
`..........................................................................................................................................................................
`
`Novo Nordisk Exhibit 2090
`Mylan Pharms. Inc. v. Novo Nordisk A/S
`IPR2023-00724
`Page 00005
`
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