2021 CCS Guidelines for management of dyslipidemia. A simplified approach

Simplified approach to review the most recent Canadian cardiovascular Society guidelines for management of dyslipidemia.

1. Review of the 2021 CCS Guidelines for the Management of Dyslipidemia. A simplified approach . Dept. of Medicine, WCGH. June 23, 2021 Alfi Moris Beshay, MD, MSc, FRCPC

2. DISCLOSURE Speaker Honoraria: Amarin , Sanofi, Astra Zeneca Stock owner: Amarin (producer of Vascepa )

3. Learning objectives: Review of the 2021 CCS Lipid Guidelines. Is there really any change in the dyslipidemia management in 2021? How much different Is the new CCS Dyslipidemia Guidelines from the ACC/AHA and the ESC Lipid Guidelines.

4. 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

5. Primary Prevention: Who & How to screen. Health Behaviour Interventions. Pharmacologic Treatment. Statin indicated Conditions Risk Assessment. Modified FRS (10Y) Cardiovascular Life Expectancy Model (CLEM) (30Y) Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

6. Secondary Prevention: Health Behaviour Interventions. Pharmacologic Treatment. Statin indicated Conditions Non-Statin add on Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

7. What’s Not New? 7 Statin therapy continues to be recommended in subjects with: clinical atherosclerosis abdominal aortic aneurysm most subjects with diabetes or chronic kidney disease Low density lipoprotein cholesterol (LDL-C) ≥5 mmol/L Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

8. What’s Not New? Contd. 8 intermediate-risk individuals with: LDL-C ≥ 3.5 mmol/L or Non-HDL-C ≥ 4.2 mmol/L or ApoB ≥ 1.05 g/L or Men ≥50 yrs and women ≥ 60 yrs with one additional risk factor: low HDL-C, IFG, high waist circumference, smoker or HTN. Health behaviour modification, including regular exercise and a heart healthy diet, remain the cornerstone of cardiovascular disease prevention Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

9. What’s New? 9 Primary Prevention: Lipoprotein(a) measurement is now recommended once in a patient's lifetime as part of initial lipid screening to assess cardiovascular risk Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

10. Apoprotein N O N POLAR LIPID CORE Cholesterol Ester Triglyceride POLAR SURFACE COAT Phospholipid Free cholesterol Lipoprotein Structure Apoprotein Apoprotein Adapted from Treatment of Heart Diseases:1992, Etiologies and Treatment of Hyperlipidemia-Scott Grundy, MD, PhD

11. Lipoprotein Sub-Classes 1.20 1.10 1.06 1.02 1.006 0.95 5 10 20 40 Particle Size (nm) 60 80 1000 C hylo m icron Remnants V L D L L DL HDL 2 HDL3DL 3 Density (g/ml) Chylomicron VLDL Remnants Lp ( a) I DL Atherogenic (found in plaque) pre-β2 HDL pre-β1 HDL

12. Lp(a) Structure Plasminogen P l a smi n Apoprotein a TG CE Polar Surface Coat (Phospholipids, F C , Apop r o t e ins ) Apo B - 100

13. What’s New? 13 Primary Prevention: Lipoprotein(a) measurement is now recommended once in a patient's lifetime as part of initial lipid screening to assess cardiovascular risk For any patient with triglycerides ˃1.5 mmol/L , the preferred lipid parameter for screening, rather than LDL-C is/are: non-high-density lipoprotein cholesterol , or apolipoprotein-B Updated recommendations regarding the role of coronary artery calcium scoring as a clinical decision tool to aid the decision to initiate statin therapy New recommendations on the preventative care of women with hypertensive disorders of pregnancy The CV benefit of icosapent ethyl in patients with TG ≥1.5 mmol/L who has DM & additional risk factor. Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

14. What’s New? 14 Primary Prevention (Contd.): The introduction of the concept of CV Risk Modifiers which include: hsCRP ≥2.0 mmol/L, family history of premature CAD, high lipoprotein(a) [ Lp (a)] ≥ 50 mg/dL (≥100 nmol/L) or CACS > 0 Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

15. What’s New? 15 Secondary Prevention: The concept of lipid/lipoprotein treatment thresholds for intensifying lipid-lowering therapy with non-statin agents . The secondary prevention patients have been shown to derive the largest benefit from intensification of therapy with these agents. The CV benefit of icosapent ethyl in patients with TG ≥1.5 mmol/L and a prior CV event. The lack of CV benefit of omega-3 fatty acids from dietary sources or other formulations/supplements. Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

16. Who to Screen

17. Who to screen for dyslipidemia in adults at risk. 1, * Men ≥40 years of age; Women ≥40 years of age (or post-menopausal) Consider earlier in ethnic groups at increased risk such as South Asian or Indigenous individuals. All patients with any of the following conditions, regardless of age: • clinical evidence of atherosclerosis • abdominal aortic aneurysm (AAA) • diabetes mellitus • arterial hypertension • current cigarette smoking • stigmata of dyslipidemia (corneal arcus, xanthelasma, xanthoma) • family history of premature CVD † • family history of dyslipidemia • chronic kidney disease (eGFR ≤60 mL/min/1.73 m 2  or ACR ≥3 mg/mmol) • obesity (BMI ≥30 kg/m 2 ) • inflammatory diseases (RA, SLE, PsA , AS, IBD) • HIV infection • erectile dysfunction • COPD • history of hypertensive disorder of pregnancy  Adapted from the 2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. † Men younger than 55 years of age and women younger than 65 years of age in first degree relatives.CVD  = cardiovascular disease; eGFR = estimated glomerular filtration rate; ACR = albumin-to-creatinine ratio; BMI = body mass index; RA = rheumatoid arthritis; SLE = systemic lupus erythematous; PsA  = psoriatic arthritis; AS = ankylosing spondylitis; IBD = inflammatory bowel disease; HIV = human immunodeficiency virus; COPD = chronic obstructive pulmonary disease Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

18. How to Screen For all: history and physical examination. standard lipid profile † :  TC, LDL-C, HDL-C, non-HDL-C * , TG FPG or A1c eGFR lipoprotein(a) – once in patient's lifetime, with initial screening. Optional: Apolipoprotein B ( ApoB ) Urine ACR (if eGFR <60 mL/min/1.73 m 2 , hypertension, or diabetes ) Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

19. Recommendations Among women who have had a pregnancy complication such as hypertensive disorders of pregnancy, gestational diabetes, pre-term birth, stillbirth, low birthweight infant, or placental abruption, we recommend screening with a complete lipid panel in the late postpartum period, since these women have a higher risk of premature CVD and stroke with onset 10-15 years after index delivery. (Strong Recommendation; Moderate Quality Evidence). We recommend counselling women who have any of these pregnancy-related complications of the increased lifetime risk of ASCVD, and reinforcing the importance of healthy beh aviours (i.e. maintaining a healthy body weight, 150 weekly minutes of moderate intensity aerobic physical activity, avoiding tobacco consumption, no more than moderate alcohol consumption, stress management, and adopting a healthy dietary pattern, such as the Mediterranean diet) (Strong Recommendation; Low Quality Evidence). To assist with decisions about lipid-lowering pharmacotherapy in this patient population, we recommend favouring CV age, over 10-year risk calculators (Strong Recommendation; Low Quality Evidence) Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

20. Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

21. Figure 5 Canadian Journal of Cardiology  2016 321263-1282DOI: (10.1016/j.cjca.2016.07.510) Copyright © 2016 Canadian Cardiovascular Society Terms and Conditions

22. Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

23. Statin therapy not recommended for most low risk individuals exceptions include: LDL-C ≥ 5.0 mmol/L (or non-HDL-C ≥ 5.8 mmol/L or ApoB ≥ 1 .45 g/L); FRS is 5%-9.9% with LDL-C ≥ 3.5 mmol/L (or non-HDL-C ≥ 4.2 mmol/L or ApoB ≥ 1.05 g/L): particularly with other CV risk modifiers : Family history of premature CAD Lp (a) ≥ 50 mg/d [or ≥ 100 nmol/L] CACs > AU

24. Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

25. Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

26. Next Slide Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

27. Pearson et al, 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult, Canadian Journal of Cardiology; https://doi.org/10.1016/j.cjca.2021.03.016

28. Thank You!

29. LDL Cholesterol > 5 mmol /L Rule out secondary causes Positive Family History First degree relative with LDL cholesterol > 5 mmol /L OR Early coronary heart disease (<65 years in women, <55 years in men) OR Physical findings in patient Obstructive liver disease Hypothyroidism Nephrotic syndrome Anorexia + - + CCS Position Statement on Familial Hypercholesterolemia (FH): Diagnostic and Treatment Flow when FH is Suspected   Genest J et al. Canadian Journal of Cardiology 2014 30, 1471-1481DOI: (10.1016/j.cjca.2014.09.028)

30. When to Consider Pharmacological Treatment in Risk Management RECOMMENDATIONS Statin indicated conditions : We recommend management that includes statin therapy in high risk conditions including clinical atherosclerosis, abdominal aortic aneurysm, most diabetes mellitus, chronic kidney disease (age >50 years) and those with LDL-C ≥5.0 mmol/L to lower the risk of CVD events and mortality (Strong Recommendation, High Quality Evidence). Primary prevention: We recommend management that does not include statin therapy for individuals at low risk (modified FRS < 10 %) to lower the risk of CVD events (Strong Recommendation, High Quality Evidence). We recommend management that includes statin therapy for individuals at high risk (modified FRS ≥ 20%) to lower the risk of CVD events (Strong Recommendation, High Quality Evidence). We recommend management that includes statin therapy for individuals at intermediate risk (IR; modified FRS 10-19%) with LDL-C ≥3.5 mmol/L to lower the risk of CVD events. Statin therapy should also be considered for IR persons with LDL-C <3.5 mmol/L but with apo B ≥1.2 g/L or non-HDL-C ≥4.3 mmol/L or in men ≥50 and women ≥60 years of age with ≥1 CV risk factor (Strong Recommendation, High Quality Evidence). Values and preferences - This recommendation applies to individuals with an LDL-C ≥1.8 mmol /L. Any decision regarding pharmacological therapy for CV risk reduction in IR persons needs to include a thorough discussion of risks, benefits, and cost of treatment, alternative nonpharmacological methods for CV risk reduction and each individual’s preference. The proportional risk reduction associated with statin therapy in RCTs in (IR) persons is of similar magnitude to that attained in high-risk persons. Moreover, irreversible severe side effects are very rare and availability of generic statins results in low cost of therapy. However, the absolute risk reduction is lower. Statin therapy may be considered in persons with FRS of 5%-9% with LDL-C ≥3.5 mmol /L or other CV risk factors as the proportional benefit from statin therapy will be similar in this group as well.

31. Figure 3 Canadian Journal of Cardiology  2016 321263-1282DOI: (10.1016/j.cjca.2016.07.510) Copyright © 2016 Canadian Cardiovascular Society Terms and Conditions

32. Apoprotein N O N POLAR LIPID CORE Cholesterol Ester Triglyceride POLAR SURFACE COAT Phospholipid Free cholesterol Lipoprotein Structure Apoprotein Apoprotein Adapted from Treatment of Heart Diseases:1992, Etiologies and Treatment of Hyperlipidemia-Scott Grundy, MD, PhD

33. Lipoprotein Sub-Classes 1.20 1.10 1.06 1.02 1.006 0.95 5 10 20 40 Particle Size (nm) 60 80 1000 C hylo m icron Remnants V L D L L DL HDL 2 HDL3DL 3 Density (g/ml) Chylomicron VLDL Remnants Lp ( a) I DL Atherogenic (found in plaque) pre-β2 HDL pre-β1 HDL

34. Figure 5 Canadian Journal of Cardiology  2016 321263-1282DOI: (10.1016/j.cjca.2016.07.510) Copyright © 2016 Canadian Cardiovascular Society Terms and Conditions

35. Lp(a) Structure Plasminogen P l a smi n Apoprotein a TG CE Polar Surface Coat (Phospholipids, F C , Apop r o t e ins ) Apo B - 100

36. Lp(a): What is It ? Why is It Dangerous ? Abnormal protein attached to LDL Genetic inheritance on Chromosome #6 One of the best predictors of Heart attack Coronary bypass surgery failure Carotid artery disease 50% of brothers/sisters and sons/daughters will have it Particularly bad if another abnormality is also present Difficult to measure accurately

37. Tsimikas, S. (2017). A Test in Context: Lipoprotein(a) Diagnosis, Prognosis, Controversies, and Emerging Therapies. Journal of the American College of Cardiology, 69 (6), 695. http://dx.doi.org/10.1016/j.jacc.2016.11.042