1. 1 ESC/EAS 2011 Guidelines for the management of dyslipidemias 2564-12-2011

2. 2 European Heart Journal Advance Access Published June 28, 2011

3. 3 Classes of recommendations DefinitionSuggested wording to use Class I ‘Everybody agrees’ Evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective. Is recommended/is indicated Class II ‘Not everybody agrees’ Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure. Class IIa Weight of evidence/opinion is in favour of usefulness/efficacy. Should be considered Class IIb Usefulness/efficacy is less well established by evidence/opinion. May be considered Class III ‘Everybody agrees’ Evidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases may be harmful. Is not recommended Classes of recommendations

4. 4 Levels of evidence Level of Evidence A Data derived from multiple randomized clinical trials or meta-analyses. Level of Evidence B Data derived from single randomized clinical trials or large non-randomized studies. Level of Evidence C Consensus of opinion of the experts and/or small studies, retrospective studies, registries.

5. 5 Risque de maladies cardiovasculaires fatales Risque à dix ans de maladies cardiovasculaires fatales pour la Belgique en fonction du sexe, de l’âge, de la pression systolique, du cholestérol et du statut tabagique FemmeHomme

6. 6 This chart may be used to show younger people at low absolute risk that, relative to others in their age group, their risk may be many times higher than necessary. This may help to motivate decisions about avoidance of smoking, healthy nutrition and exercise, as well as flagging those who may become candidates for medication. Please note that this chart shows RELATIVE not absolute risk. The risks are RELATIVE to 1 in the bottom left. Thus a person in the top right hand box has a risk that is 12 times higher than a person in the bottom left. Relative Risk Chart < 40y ESC 2007

7. 7 Recommendations for treatment targets for LDL-C Recommendations Class a Level b Ref c In patients at VERY HIGH CV risk (established CVD, type 2 diabetes, type 1 diabetes with target organ damage, moderate to severe CKD or a SCORE level ≥10%) the LDL-C goal is <1.8 mmol/L (less than ~ 70 mg/dL) and/or ≥ 50% LDL-C reduction when target level cannot be reached. IA15,32,33 In patients at HIGH CV risk (markedly elevated single risk factors, a SCORE level ≥5 to <10%) an LDL-C goal <2.5 mmol/L (less than ~ 100 mg/dL) should be considered. IIaA15,16,17 In subjects at MODERATE risk (SCORE level >1 to ≤5%) an LDL-C goal < 3.0 mmol/L (less than ~ 115 mg/dL) should be considered. IIaC- a Class of recommendation. b Level of evidence. c References. CKD= chronic kidney disease; CV = cardiovascular; CVD = cardiovascular disease; LDL-C = low-density lipoprotein-cholesterol

8. 8 Recommendations for treatment targets for LDL-C Recommendations Class a Level b Ref c In patients at VERY HIGH CV risk (established CVD, type 2 diabetes, type 1 diabetes with target organ damage, moderate to severe CKD or a SCORE level ≥10%) the LDL-C goal is <1.8 mmol/L (less than ~ 70 mg/dL) and/or ≥ 50% LDL-C reduction when target level cannot be reached. IA15,32,33 a Class of recommendation. b Level of evidence. c References. CKD= chronic kidney disease; CV = cardiovascular; CVD = cardiovascular disease; LDL-C = low-density lipoprotein-cholesterol

9. 9 Recommendations for treatment targets for LDL-C Recommendations Class a Level b Ref c In patients at HIGH CV risk (markedly elevated single risk factors, a SCORE level ≥5 to <10%) an LDL-C goal <2.5 mmol/L (less than ~ 100 mg/dL) should be considered. IIaA15,16,17 In subjects at MODERATE risk (SCORE level >1 to ≤5%) an LDL-C goal < 3.0 mmol/L (less than ~ 115 mg/dL) should be considered. IIaC- a Class of recommendation. b Level of evidence. c References. CKD= chronic kidney disease; CV = cardiovascular; CVD = cardiovascular disease; LDL-C = low-density lipoprotein-cholesterol

10. 10 * In patients with MI, statin therapy should be considered irrespective of LDL-C levels. a Class of recommendation. b Level of evidence. Intervention strategies as a function of total CV risk and LDL-C level CV = cardiovascular; LDL-C = low-density lipoprotein-cholesterol; MI = myocardial infarction. TOTAL CV risk (SCORE) % LDL-C levels <70 mg/dL <1.8 mmol/L 70 to <100 mg/dL 1.8 to <2.5 mmol/L 100 to <155 mg/dL 2.5 to < 4.0 mmol/L 155 to < 190 mg/dL 4.0 to < 4.9 mmol/L >190 mg/dL >4.9 mmol/L <1 No lipid intervention Lifestyle intervention Lifestyle intervention, consider drug if uncontrolled Class a /Level b I/C IIa/A ≥ 1 to < 5 Lifestyle intervention Lifestyle intervention, consider drug if uncontrolled Class a /Level b I/C IIa/A I/A >5 to <10, or high risk Lifestyle intervention, consider drug* Lifestyle intervention, and immediate drug intervention Class a /Level b IIa/A I/A ≥10 or very high risk Lifestyle intervention, consider drug* Lifestyle intervention, and immediate drug intervention Class a /Level b IIa/A I/A

11. 11 Addendum II. Practical approach to reach LDL-C goal Percentage reduction of LDL-C requested to achieve goals as a function of the starting value Starting LDL-C% Reduction to reach LDL-C mmol/L ~ mg/mL <1.8 mmol/L ( ~ 70mg/dL) <2.5 mmol/L ( ~ 100mg/dL) <3 mmol/L ( ~ 115mg/dL) >6.2>240>70>60>55 5.2-6.2200-24065-7050-6040-55 4.4-5.2170-20060-6540-5030-45 3.9-4.4150-17055-6035-4025-30 3.4-3.9130-15045-5525-3510-25 2.9-3.4110-13035-4510-25<10 2.3-2.990-11022-35<10- 1.8-2.370-90<22--

12. 12 LDL-C

13. 13 LDL-C: Percentage Change from Baseline at Week 6 (n=2240) LS mean % change from baseline -60 -50 -40 -30 -20 -10 0 10204080 Dose (mg) Log scale rosuvastatinatorvastatinsimvastatinpravastatin Jones et al. Am J Cardiol 2003: 93: 152-160

14. 14 SCORE 2011 Women High Risk

15. 15 0 2 4 6 8 10 12 10204080 Dose (mg) LS mean % change from baseline Log scale HDL-C: Percentage Change from Baseline at Week 6 (n= 2240) Jones et al. Am J Cardiol 2003: 93: 152-160 rosuvastatinatorvastatinsimvastatinpravastatin

16. 16 Taux HDL-C, mg/dl 30 38 46 54 62 70 Femme x 1,8 x 1,5 x 1,2 x 1 x 0,8 x 0,7 Homme x 1,3 x 1,1 x 1 x 0,9 x 0,8 x 0,7 l’effet du cholestérol associé aux lipoprotéines de haute densité (HDL-C) sur le risque CV global

17. 17 Statins are among the most studied drugs in CV prevention, and dealing with single studies is beyond the scope of the present guidelines. A number of large-scale clinical trials have demonstrated that statins substantially reduce CV morbidity and mortality in both primary and secondary prevention. Statins have also been shown to slow the progression or even promote regression of coronary atherosclerosis. Statins Efficacy in clinical studies

18. 18 Current available evidence suggests that the clinical benefit is largely independent of the type of statin but depends on the extent of LDL-C lowering; therefore, the type of statin used should reflect the degree of LDL-C reduction that is required to reach the target LDL-C in a given patient. More details on this are provided in Addendum II to these guidelines. Statins Meta-analyses

19. 19 The recent finding that the incidence of diabetes may increase with statins should not discourage institution of treatment; the absolute reduction in the risk of CVD in high risk patients outweighs the possible adverse effects of a very small increase in the incidence of diabetes. Statins Meta-analyses - Type 2 Diabetes

20. 20 Cholesterol absorption inhibitors Efficacy in clinical studies Ezetimibe can be used as second-line therapy in association with statins when the therapeutic target is not achieved at maximal tolerated statin dose or in patients intolerant of statins or with contraindications to these drugs.

21. 21 Management of hypertriglyceridaemia Pharmacological therapy As statins have significant effects on mortality as well as most CVD outcome parameters, these drugs are the first choice to reduce both total CVD risk and moderately elevated TG levels. More potent statins (atorvastatin, rosuvastatin, and pitavastatin) demonstrate a robust lowering of TG levels, especially at high doses and in patients with elevated TG.

22. 22 Recommendations for treatment of dyslipidaemia in diabetes Recommendations Class a Level b Ref c In all patients with type I diabetes and in the presence of microalbuminuria and renal disease, LDL-C lowering (at least 30%) with statins as the first choice (eventually drug combination) is recommended irrespective of the basal LDL-C concentration. IC In patients with type 2 diabetes and CVD or CKD, and in those without CVD who are over the age of 40 years with one or more other CVD risk factors or markers or target organ damage, the recommended goal for LDL-C is <1.8 mmol/L (less than ~ 70 mg/dL) and the secondary goal for non-HDL-C is <2.6 mmol/L (100 mg/dL) and for apo B is <80 mg/dL. IB15,16 In all people with type 2 diabetes LDL-C <2.5 mmol/L (less than ~ 100 mg/dL) is the primary target. Non-HDL-C <3.3 mmol/L (130 mg/dL) and apo B <100 mg/dL are the secondary targets. I B15,16

23. 23 Le risque sera également plus élevé qu’indiqué dans les tableaux pour : Les personnes socialement défavorisées ; les privations induisent de nombreux autres facteurs de risque. Les sujets sédentaires et ceux présentant une obésité abdominale ; ces caractéristiques déterminent de nombreux autres aspects des risques énumérés ci-dessous. Les personnes diabétiques : une nouvelle analyse de la base de données SCORE indique que les personnes présentant un diabète avéré ont un risque nettement plus élevé ; cinq fois plus élevé pour les femmes et trois fois plus élevé pour les hommes. Les personnes ayant un faible taux d’HDL-C ou d’apolipoprotéine A1 (apo A1), des taux élevés de TG, de fibrinogène, d’homocystéine, d’ apolipoprotéine B (apo B) et de lipoprotéine(a) (Lp(a)), une hypercholestérolémie familiale (HF) ou un taux élevé de hs-CRP ; ces facteurs indiquent un niveau de risque accru pour les deux sexes, pour toutes les tranches d’âge et pour tous les niveaux de risque.

24. 24 Les personnes asymptomatiques présentant des signes précliniques d’athérosclérose, par exemple la présence de plaques ou un épaississement de l’intima–média carotidienne détecté lors d’une échographie carotidienne. Les personnes atteintes d’insuffisance rénale. Les personnes ayant des antécédents familiaux de MCV précoce dont on considère qu’ils multiplient le risque par 1,7 chez les femmes et par 2,0 chez les hommes. À l’inverse, le risque peut être inférieur à celui indiqué chez les personnes ayant des taux très élevés d’HDL-C ou des antécédents familiaux de longévité.

25. 25 Risk factor management in coronary patients – results from a European wide survey EUROASPIRE III Professor David A Wood on behalf of the EUROASPIRE Investigators

26. 26 Distribution of Age, Gender and Diagnostic Category (%) (years) GenderAgeDiagnostic category

27. 27 Prevalence of Smoking* P=0.64 S2 vs. S1 : P=0.83 S3 vs. S2 : P=0.37 S3 vs. S1 : P=0.48 * Self-reported smoking or CO in breath > 10 ppm

28. 28 Prevalence of Overweight* P=0.04 S2 vs. S1 : P=0.15 S3 vs. S2 : P=0.22 S3 vs. S1 : P=0.02 * Body mass index ≥ 25 kg/m²

29. 29 Prevalence of Obesity* P=0.0006 S2 vs. S1 : P=0.009 S3 vs. S2 : P=0.051 S3 vs. S1 : P=0.0002 * Body mass index ≥ 30 kg/m²

30. 30 Prevalence of Raised Blood Pressure (1)* P=0.79 S2 vs. S1 : P=0.83 S3 vs. S2 : P=0.51 S3 vs. S1 : P=0.65 * SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg

31. 31 Therapeutic Control of Blood Pressure* P=0.57 S2 vs. S1 : P=0.98 S3 vs. S2 : P=0.36 S3 vs. S1 : P=0.37 * SBP/DBP < 140/90 mmHg for non-diabetics or < 130/80 mmHg for diabetics

32. 32 Prevalence of Raised Total Cholesterol* P<0.0001 S2 vs. S1 : P<0.0001 S3 vs. S2 : P<0.0001 S3 vs. S1 : P<0.0001 * Total cholesterol ≥ 4.5 mmol/L

33. 33 Therapeutic Control of Total Cholesterol* P<0.0001 S2 vs. S1 : P<0.0001 S3 vs. S2 : P<0.0001 S3 vs. S1 : P<0.0001 * Total cholesterol < 4.5 mmol/L

34. 34 Prevalence of Diabetes* P=0.004 S2 vs. S1 : P=0.21 S3 vs. S2 : P=0.02 S3 vs. S1 : P=0.001 * Self-reported history of diagnosed diabetes

35. 35 Therapeutic Control of Diabetes* P=0.04 S2 vs. S1 : P=0.82 S3 vs. S2 : P=0.03 S3 vs. S1 : P=0.08 * Fasting glucose < 7 mmol/L in patients with history of diabetes

36. 36 Medication Use: Antiplatelets P<0.0001S2 vs. S1 : P=0.29 S3 vs. S2 : P=0.0002 S3 vs. S1 : P<0.0001

37. 37 Medication Use: Beta-Blockers P<0.0001S2 vs. S1 : P=0.001 S3 vs. S2 : P=0.0002 S3 vs. S1 : P<0.0001

38. 38 Medication Use: ACE Inhibitors & Angiotensin II RA P<0.0001 S2 vs. S1 : P<0.0001 S3 vs. S2 : P<0.0001 S3 vs. S1 : P<0.0001

39. 39 Medication Use: Statins P<0.0001 S2 vs. S1 : P<0.0001 S3 vs. S2 : P<0.0001 S3 vs. S1 : P<0.0001

40. 40 Medication Use: Diuretics P=0.006 S2 vs. S1 : P=0.30 S3 vs. S2 : P=0.02 S3 vs. S1 : P=0.002

41. 41  No change in blood pressure control despite increased use of anti-hypertensive medications  61% above therapeutic target  (BP < 140/90 mmHg)  Continuing improvement in lipid control with increased use of statins  42% above the 2003 therapeutic target (TC < 4.5 mmol/l) Conclusions

42. 42 ESH - ESC Guidelines, J Hypertens 2003 -BP< 140/90 mmHg in all hypertensive patients < 130/80 mmHg in hypertensive patients with diabetes or renal disease -Control of all cardiovascular risk factors -BP< 140/90 mmHg in all hypertensive patients < 130/80 mmHg in hypertensive patients with diabetes or renal disease -Control of all cardiovascular risk factors Goals of treatment

43. 43 Sympathetic nervous system Renin-angiotensin system Total body sodium Sympathetic nervous system Renin-angiotensin system Total body sodium Patient 1 Patient 2 Patient 3

44. 44 Percentage of patients with normal blood pressure Percentage of patients with normal blood pressure Drug A 020406080100 % % Drugs C Drug B

45. 45 Achieved BP: <140/90 mmHg Dickerson et al, Lancet, 1999 During monotherapy (diuretic,  -blocker, ACE inhibitor or Ca antagonist) During monotherapy (diuretic,  -blocker, ACE inhibitor or Ca antagonist) % % 39 0 0 20 40 60 80 BP control rate during antihypertensive monotherapy

46. 46 Percentage of patients with normal blood pressure Percentage of patients with normal blood pressure Drug A 020406080100 % % Drugs A + B Drug B

47. 47 Systolic Diastolic Systolic Diastolic 0 -5 -10 -5 Effects of two different drugs on BP separately and in combination (119 randomized placebo controlled trials) Placebo- subtracted BP response. mmHg Law et al, BMJ 2003 "First" drug alone "Second" drug alone Combinati on

48. 48 Advantages of fixed versus liberal combinations of two antihypertensive drugs FixedLiberal Simplicity of treatment+- Compliance+- Efficacy++ Tolerability+*- Price+- Flexibility-+ Risk of administering +- contraindicated drug FixedLiberal Simplicity of treatment+- Compliance+- Efficacy++ Tolerability+*- Price+- Flexibility-+ Risk of administering +- contraindicated drug *lower doses generally used in fixed-dose combinations

49. 49 Pharmacological treatment of hypertension Consider : Blood pressure level before treatment Absence or presence of TOD and risk factors Consider : Blood pressure level before treatment Absence or presence of TOD and risk factors 2003 European Society of Hypertension - European Society of Cardiology Guidelines for the Management of Arterial Hypertension, J Hypertens, 2003 Two-drug combination at low dose Choose between : Single agent at low dose If goal BP not achieved : Previous agent at full dose Switch to different agent at low dose Previous combinati on at full dose Add a third drug at low dose If goal BP not achieved : Two-three drug combination

50. 50 Stage 1 hypertension (SBP 140-159 or DBP 90-99 mmHg) Thiazide-type diuretics for most, consider ACE inhibitor, ARB,  -blocker, CCB, or combination Stage 1 hypertension (SBP 140-159 or DBP 90-99 mmHg) Thiazide-type diuretics for most, consider ACE inhibitor, ARB,  -blocker, CCB, or combination Stage 2 hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg) 2-drug combination for most (usually thiazide-type diuretic and ACE inhibitor or ARB or  - blocker or CCB) Stage 2 hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg) 2-drug combination for most (usually thiazide-type diuretic and ACE inhibitor or ARB or  - blocker or CCB) Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACE inhibitor, ARB,  -blocker, CCB) as needed Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACE inhibitor, ARB,  -blocker, CCB) as needed Not at goal BP Lifestyle modifications Algorithm for treatment of hypertension The JNC VII Report, 2003 Not at goal BP (<140/90 mmHg or <130/80 mmHg for those with diabetes or chronic kidney disease) Initial drug choices Hypertension with compelling indications Hypertension without compelling indications Optimize dosages or add additional drugs until goal BP is achieved Consider consultation with hypertension specialist Optimize dosages or add additional drugs until goal BP is achieved Consider consultation with hypertension specialist

51. 51 SATISFACTION Normalization of BP Normalization of BP Good tolerability Good tolerability Simple drug regimen Simple drug regimen Day-to-day compliance  Long-term compliance 