ESC/EAS 2011 Guidelines for the management of dyslipidemias

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

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

3. Classes of recommendations

4. Levels of evidence

5. Risque de maladies cardiovasculaires fatales Risque à dixans de maladies cardiovasculaires fatales pour la Belgique en fonction du sexe, de l’âge, de la pressionsystolique, du cholestérol et du statuttabagique Femme Homme

6. Relative Risk Chart < 40y 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. ESC 2007

7. Recommendations for treatment targets for LDL-C aClass of recommendation. bLevel of evidence. cReferences. CKD= chronic kidney disease; CV = cardiovascular; CVD = cardiovascular disease; LDL-C = low-density lipoprotein-cholesterol

8. Recommendations for treatment targets for LDL-C aClass of recommendation. bLevel of evidence. cReferences. CKD= chronic kidney disease; CV = cardiovascular; CVD = cardiovascular disease; LDL-C = low-density lipoprotein-cholesterol

9. Intervention strategies as a function of total CV risk and LDL-C level *In patients with MI, statin therapy should be considered irrespective of LDL-C levels. aClass of recommendation. bLevel of evidence. CV = cardiovascular; LDL-C = low-density lipoprotein-cholesterol; MI = myocardial infarction.

10. Addendum II. Practical approach to reach LDL-C goal

11. LDL-C

12. LDL-C: Percentage Change from Baseline at Week 6 (n=2240) Dose (mg) Log scale 10 20 40 80 0 -10 -20 -30 LS mean % change from baseline -40 -50 -60 rosuvastatin atorvastatin simvastatin pravastatin Jones et al. Am J Cardiol 2003: 93: 152-160

13. SCORE 2011 Women High Risk

14. HDL-C: Percentage Change from Baseline at Week 6 (n= 2240) 12 10 8 LS mean % change from baseline 6 4 2 0 Log scale 10 20 40 80 Dose (mg) rosuvastatin atorvastatin simvastatin pravastatin Jones et al. Am J Cardiol 2003: 93: 152-160

15. l’effet du cholestérol associé aux lipoprotéines de haute densité (HDL-C) sur le risque CV global 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

16. Statins Efficacy in clinical studies 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.

17. Statins Meta-analyses 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.

18. Statins Meta-analyses - Type 2 Diabetes 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.

19. Cholesterol absorption inhibitorsEfficacy 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.

20. Management of hypertriglyceridaemiaPharmacological 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.

21. 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.

22. • 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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

39. Conclusions • 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)

40. Goals of treatment -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 ESH - ESC Guidelines, J Hypertens 2003

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

42. Percentage of patients with normal blood pressure Drug A Drug B Drugs C % 0 20 40 60 80 100

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

44. Percentage of patients with normal blood pressure Drug A Drug B Drugs A + B % 0 20 40 60 80 100

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

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

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

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

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