THE ESC/EAS LIPID GUIDELINES IN THE ELDERLY Alberico L. Catapano alberico.catapano@unimi.it
Alberico L. Catapano Potential Conflict Of Interest Prof. Catapano has received honoraria, lecture fees, or research grants from: Abbot, Aegerion, Amgen, AstraZeneca, Bayer, Eli Lilly, Genzyme, Ionis, Kowa, Mediolanum, Meda,Menarini, Merck, Pfizer, Recordati, Regeneron, Sanofi, SigmaTau.
LDL-C is a major causal factor for atherosclerotic CVD LDL-C: primary risk factor in CHD and causative for development of coronary atherosclerosis 6 Hypertension 1 Smoking, physical inactivity 1 Prior CV event/manifest atherosclerosis 3 Age, ethnicity, gender, family history/genetic variations 1 Lipid disorders 1 (LDL, HDL, TG ) Increased CV risk Metabolic syndrome 2 Type 2 diabetes 1 High CRP, 4 chronic kidney disease 5 Obesity 1
LDL : a major modifiable cardiovascular risk factor Meta-analysis of 61 prospective studies in the general population (n = 892,237) Lancet 2007;370:1829-39
Proportional reduction in CHD risk (log scale) Genetic evidence supports LDL-C as a risk factor for CV events 54.5% reduction in CHD risk per 1mmol/L lower LDL-C 30% Genetically lower LDL-C PCSK9 46L rs11591147 20% ABCG5/8 rs4299376 LDLR rs2228671 NPC1L1 LDL-C score HMGCR LDL-C score 10% HMGCR rs12916 PCSK9 rs2479409 NPC1L1 rs217386 PCSK9 rs11206510 HMGCR LDL-C score NPC1L1 LDL-C score LDLR rs6511720 Combined NPC1L1 & HMGCR LDL-C score 0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 12.0 13.0 14.0 15.0 16.0 17.0 18.0 19.0 20.0 21.0 Absolute magnitude of lower LDL-C (mg/dl) Ference et al. J Am Coll Cardiol 2012;60:2631 2639. Ference et al. J Am Coll Cardiol 2015;65:1552 1561.
Proportional reduction in CHD risk (log scale) Clinical benefit of lower LDL is determined by absolute exposure to lower LDL 30% 54.5% reduction in CHD risk for each 1mmol/L (38mg/dL) lower LDL-C 20% 10% PCSK9 rs2479409 NPC1L1 rs217386 ABCG5/8 rs4299376 HMGCR rs12916 LDLR rs2228671 PCSK9 rs11206510 NPC1L1 LDL-C score HMGCR LDL-C score HMGCR LDL-C score NPC1L1 LDL-C score Genetically lower LDL-C LDLR rs6511720 Combined NPC1L1 & HMGCR LDL-C score A to Z GISSI-P SEARCH PCSK9 46L rs11591147 Pharmacologically lower LDL-C IMPROVE-IT ALLHAT-LLT 17.2% reduction in CHD risk for each 1mmol/L (38mg/dL) lower LDL-C 0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 12.0 13.0 14.0 15.0 16.0 17.0 18.0 19.0 20.0 21.0 Lower LDL-C (mg/dl) Ference et al. J Am Coll Cardiol 2015;65:1552 1561.
Proportional Reduction in Event Rate (SE) Greater reductions in LDL-C levels are associated with greater reductions in CV event rates 50% 40% 30% 20% CTT-meta-analysis 10% 0% IMPROVE-IT 19 39 58 77 Reduction in LDL-C (mg/dl) CTTC. Lancet 2005;366:1267 1278. CTTC. Lancet 2010;376:1670 1681. Cannon et al. N Engl J Med 2015;372:2387 2397.
Weighted Between-Group Difference in Achieved Low- Density Lipoprotein Cholesterol (LDL-C) Level and Relative Risk for Major Vascular Events for Each Class of Intervention Silverman MG. et al. JAMA. 2016;316:1289-97
Scatterplot of absolute LDL-C reduction and major vascular event (MVE) relative risk for each trial Silverman MG. et al. JAMA. 2016;316:1289-97 - Supplementary Online Content
Effects of lowering LDL cholesterol with statin therapy on cause-specific mortality in metaanalyses of randomised trials of statin therapy Collins R. et al. Lancet 2016 Epub Sep 6
Similar proportional reductions in risks of major vascular events per mmol/l LDL cholesterol reduction in randomised trials of statin therapy among people with different presenting characteristics Collins R. et al. Lancet 2016 Epub Sep 6
Proportional reductions in risks of major vascular events per mmol/l reduction in LDL cholesterol during each year of scheduled statin treatment, in randomised trials of routine statin therapy versus no routine statin use Collins R. et al. Lancet 2016 Epub Sep 6
Predicted absolute reductions in risks of major vascular events (after the first year) by lowering LDL cholesterol with statin therapy for 5 years in people at different levels of absolute risk Collins R. et al. Lancet 2016 Epub Sep 6
15 2016 ESC/EAS Guidelines for the management of dyslipidaemias The Task Force of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR) Task Force Members: A L. Catapano* (Chairperson) (Italy), I Graham* (Chairperson) (Ireland), G De Backer (Belgium), O Wiklund (Sweden), M. J Chapman (France), H Drexel (Austria), A W. Hoes (The Netherlands), C S. Jennings (UK), U Landmesser (Germany), T R. Pedersen (Norway), Ž Reiner (Croatia), G Riccardi (Italy), M-R Taskinen (Finland), L Tokgozoglu (Turkey), W. M. M Verschuren (The Netherlands), Ch Vlachopoulos (Greece), D A. Wood (UK), J L Zamorano (Spain). Additional Contributor: M T Cooney (Ireland)
2016 ESC/EAS Guidelines for the management of dyslipidaemias 16 Table of content: -What is cardiovascular disease prevention? -Total cardiovascular risk -Evaluation of laboratory lipid and apolipoprotein parameters -Treatment targets -Lifestyle modifications to improve the plasma lipid profile -Drugs for treatment of hypercholesterolaemia -Drugs for treatment of hypertriglyceridaemia -Drugs affecting high-density lipoprotein-cholesterol -Management of dyslipidaemia in different clinical settings -Monitoring of lipids and enzymes in patients on lipid-lowering therapy -Strategies to encourage adoption of healthy lifestyle changes and adherence to lipid modifying therapies
Systolic blood pressure SCORE chart: 10-year risk fatal cardiovascular disease (CVD) in population at high CVD risk Women Men Non-smoker Smoker Age Non-smoker Smoker 180 160 140 120 7 8 9 10 12 5 5 6 7 8 3 3 4 5 6 2 2 3 3 4 13 15 17 19 22 9 10 12 13 16 6 7 8 9 11 4 5 5 6 7 65 14 16 19 22 26 9 11 13 15 16 6 8 9 11 13 4 5 6 7 9 26 30 35 41 47 18 21 25 29 34 13 15 17 20 24 9 10 12 14 17 SCORE 180 160 140 120 180 160 140 120 4 4 5 6 7 3 3 3 4 5 2 2 2 3 3 1 1 2 2 2 2 2 3 3 4 1 2 2 2 3 1 1 1 1 2 1 1 1 1 1 8 9 10 11 13 5 6 7 8 9 3 4 5 5 6 2 3 3 4 4 4 5 5 6 7 3 3 4 4 5 2 2 2 3 3 1 1 2 2 2 60 55 9 11 13 15 18 6 7 9 10 12 4 5 6 7 9 3 3 4 5 6 6 7 8 10 12 4 5 6 7 8 3 3 4 5 6 2 2 3 3 4 18 21 24 28 33 12 14 17 20 24 8 10 12 14 17 6 7 8 10 12 12 13 16 19 22 8 9 11 13 16 5 6 8 9 11 4 4 5 6 8 15% and over 10%-14% 5%-9% 3%-4% 2% 1% <1% 10-year risk of fatal 180 160 140 120 1 1 1 2 2 1 1 1 1 1 0 1 1 1 1 0 0 1 1 1 2 2 3 3 4 1 2 2 2 3 1 1 1 1 2 1 1 1 1 1 50 4 4 5 6 7 2 3 3 4 5 2 2 2 3 3 1 1 2 2 2 7 8 10 12 14 5 6 7 8 10 3 4 5 6 7 2 3 3 4 5 CVD in populations at High CVD risk 180 160 140 120 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 40 1 1 1 2 2 1 1 1 1 1 0 1 1 1 1 0 0 1 1 1 2 2 3 3 4 1 2 2 2 3 1 1 1 2 2 1 1 1 1 1 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 Cholesterol (mmol/l) 150 200 250 300 mg/dl
Systolic blood pressure 18 The risk age concept Women Men SCORE 180 160 140 120 180 160 140 120 Non-smoker 7 8 9 10 12 5 5 6 7 8 3 3 4 5 6 2 2 3 3 4 4 4 5 6 7 3 3 3 4 5 2 2 2 3 3 1 1 2 2 2 Smoker 13 15 17 19 22 9 10 12 13 16 6 7 8 9 11 4 5 5 6 7 8 9 10 11 13 5 6 7 8 9 3 4 5 5 6 2 3 3 4 4 Age 65 60 Non-smoker 14 16 19 22 26 9 11 12 15 16 6 8 9 11 13 4 5 6 7 9 9 11 13 15 18 6 7 9 10 12 4 5 6 7 9 3 3 4 5 6 Smoker 26 30 35 41 47 18 21 25 29 34 13 15 17 20 24 9 10 12 14 17 18 21 24 28 33 12 14 17 20 24 8 10 12 14 17 6 7 8 10 12 15% and over 10%-14% 5%-9% 3%-4% 2% 1% <1% 10-year risk of fatal CVD in populations at High CVD risk 180 160 140 120 180 160 140 120 2 2 3 3 4 1 2 2 2 3 1 1 1 1 2 1 1 1 1 1 1 1 1 2 2 1 1 1 1 1 0 1 1 1 1 0 0 1 1 1 4 5 5 6 7 3 3 4 4 5 2 2 2 3 3 1 1 2 2 2 2 2 3 3 4 1 2 2 2 3 1 1 1 1 2 1 1 1 1 1 55 50 6 7 8 10 12 4 5 6 7 8 3 3 4 5 6 2 2 3 3 4 4 4 5 6 7 2 3 3 4 5 2 2 2 3 3 1 1 2 2 2 12 13 16 19 22 8 9 11 13 16 5 6 8 9 11 4 4 5 6 8 7 8 10 12 14 5 6 7 8 10 3 4 5 6 7 2 3 3 4 5 The risk of this 40 year old male smoker with risk factors is the same (3%) as that of a 60 year old man with ideal risk factor levels therefore his risk age is 60 years. 180 160 140 120 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 40 1 1 1 2 2 1 1 1 1 1 0 1 1 1 1 0 0 1 1 1 2 2 3 3 4 1 2 2 2 3 1 1 1 2 2 1 1 1 1 1 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 4 5 6 7 8 Cholesterol (mmol/l) 150 200 250 300 mg/dl
Risk function without high-density lipoproteincholesterol (HDL-C) for men Non-smoker Age Smoker Without HDL HDL 0.8 HDL 1.0 HDL 1.4 HDL 1.8 5.1 6.6 5.9 4.9 4.1 180 160 140 120 13 14 16 19 22 9 10 12 14 16 6 7 8 10 11 4 5 6 7 8 65 22 24 28 32 36 16 18 20 23 27 11 13 15 17 20 8 9 11 12 15 Without HDL HDL 0.8 HDL 1.0 HDL 1.4 HDL 1.8 9.1 11.6 10.4 8.5 7.2 Without HDL HDL 0.8 HDL 1.0 HDL 1.4 HDL 1.8 4.4 5.6 5.0 4.1 3.5 180 160 140 120 9 10 12 14 16 6 7 8 10 12 4 5 6 7 8 3 4 4 5 6 60 15 18 20 24 28 11 13 15 17 20 8 9 11 13 15 6 6 8 9 11 Without HDL HDL 0.8 HDL 1.0 HDL 1.4 HDL 1.8 5.5 7.0 6.3 5.1 4.3 Without HDL HDL 0.8 HDL 1.0 HDL 1.4 HDL 1.8 4.6 6.1 5.4 4.3 3.5 180 160 140 120 6 6 8 9 11 4 5 5 7 8 3 3 4 5 6 2 2 3 3 4 55 10 12 14 16 19 7 8 10 12 14 5 6 7 9 10 4 4 5 6 7 Without HDL HDL 0.8 HDL 1.0 HDL 1.4 HDL 1.8 5.1 6.8 6.0 4.6 3.6 Without HDL HDL 0.8 HDL 1.0 HDL 1.4 HDL 1.8 3.6 4.6 4.2 3.4 2.8 180 160 140 120 4 4 5 6 7 3 3 3 4 5 2 2 2 3 4 1 1 2 2 3 50 6 7 9 11 13 5 5 6 8 9 3 4 5 5 7 2 3 3 4 5 Without HDL HDL 0.8 HDL 1.0 HDL 1.4 HDL 1.8 4.7 6.6 5.9 4.6 3.6 Systolic blood pressure (mmhg) 180 160 140 120 1 1 1 2 2 1 1 1 1 1 1 1 1 1 1 0 0 0 1 1 4 5 6 7 8 40 2 2 3 3 4 1 2 2 2 3 1 1 1 2 2 1 1 1 1 1 4 5 6 7 8 Without HDL HDL 0.8 HDL 1.0 HDL 1.4 HDL 1.8 3.7 4.9 4.3 3.3 2.6 Total Cholesterol (mmol/l)
Risk categories 20 Very high-risk Subjects with any of the following: Documented CVD, clinical or unequivocal on imaging. Documented clinical CVD includes previous AMI, ACS, coronary revascularization and other arterial revascularization procedures, stroke and TIA, aortic aneurysm and PAD. Unequivocally documented CVD on imaging includes significant plaque on coronary angiography or carotid ultrasound. It does NOT include some increase in continuous imaging parameters such as intima media thickness of the carotid artery. DM with target organ damage such as proteinuria or with a major risk factor such as smoking or marked hypercholesterolaemia or marked hypertension. Severe CKD (GFR <30 ml/min/1.73 m 2 ). A calculated SCORE >10%.
Risk categories 21 High-risk Subjects with: Markedly elevated single risk factors such as familial dyslipidaemias and severe hypertension. Most other people with diabetes (some young people with type 1 diabetes may be at low or moderate risk). Moderate CKD (GFR 30 59 ml/min/1.73 m 2 ). A calculated SCORE 5% and < 10% for 10- year risk of fatal CVD. Moderaterisk Low-risk Subjects are considered to be at moderate risk when their SCORE is 1% and < 5% at 10 years. Many middle-aged subjects belong to this risk category. The low risk category applies to individuals with SCORE < 1%
22 2016 ESC/EAS Guidelines for the management of dyslipidaemias Table of content: - What is cardiovascular disease prevention? - Total cardiovascular risk - Evaluation of laboratory lipid and apolipoprotein parameters - Treatment targets - Lifestyle modifications to improve the plasma lipid profile - Drugs for treatment of hypercholesterolaemia - Drugs for treatment of hypertriglyceridaemia - Drugs affecting high-density lipoprotein-cholesterol - Management of dyslipidaemia in different clinical settings - Monitoring of lipids and enzymes in patients on lipid-lowering therapy - Strategies to encourage adoption of healthy lifestyle changes and adherence to lipid modifying therapies
23 Lipid analyses as treatment targets Recommendations Class Level Non-HDL-C should be considered as a secondary treatment target. ApoB should be considered as a secondary treatment target, whenavailable. HDL-C is not recommended as a target for treatment. The ratios apob/apoa1 and non-hdl-c/hdl-c are not recommended as targets for treatment. IIa IIa III III B B A B
24 Treatment goals for LDL-cholesterol Recommendations Class Level In patients at VERY HIGH CV risk, an LDL-C goal of <1.8 mmol/l (70 mg/dl) or a reduction of at least 50% if the baseline LDL-C is between 1.8 and 3.5 mmol/l (70 and 135 mg/dl) is recommended. In patients at HIGH CV risk, an LDL-C goal of <2.6 mmol/l (100 mg/dl), or a reduction of at least 50% if the baseline LDL- C is between 2.6 and 5.2 mmol/l (100 and 200 mg/dl) is recommended. I I B B In subjects at LOW or MODERATE risk an LDL-C goal of <3.0 mmol/l ( <115 mg/dl) should be considered. IIa C
25 Intervention strategies Total CV risk (SCORE) % <70 mg/dl <1.8 mmol/l 70 to <100 mg/dl 1.8 to <2.6 mmol/l LDL-C levels 100 to <155 mg/dl 2.6 to <4.0 mmol/l 155 to <190 mg/dl 4.0 to <4.9 mmol/l <1 Lifestyle advice Lifestyle advice Lifestyle advice Lifestyle advice 190 mg/dl 4.9 mmol/l Lifestyle advice, consider drug if uncontrolled Class/Level I/C I/C I/C I/C IIa/A 1 to <5 Lifestyle advice Lifestyle advice Lifestyle advice, consider drug if uncontrolled Lifestyle advice, consider drug if uncontrolled Lifestyle advice, consider drug if uncontrolled Class/Level I/C I/C IIa/A IIa/A I/A 5 to <10, or high-risk Lifestyle advice Lifestyle advice, consider drug if uncontrolled Lifestyle advice and drug treatment for most Lifestyle advice and drug treatment Lifestyle advice and drug treatment Class/Level IIa/A IIa/A IIa/A I/A I/A 10 or very high-risk Lifestyle advice, consider drug a Lifestyle advice and concomitant drug treatment Lifestyle advice and concomitant drug treatment Lifestyle advice and concomitant drug treatment Lifestyle advice and concomitant drug treatment Class/Level IIa/A IIa/A I/A IA I/A a In patients with myocardial infarction, statin therapy should be considered irrespective of total cholesterol levels.
Recommendations for the pharmacological treatment of elevated LDL-cholesterol Prescribe statin up to the highest recommended dose or highest tolerable dose to reach the goal. In the case of statin intolerance, ezetimibe or bile acid sequestrants, or these combined, should be considered. If goal is not reached, statin combination with a cholesterol absorption inhibitor should be considered. If goal is not reached, statin combination with a bile acid sequestrant may be considered. In patients at very high risk, with persistent high LDL- C despite treatment with maximal tolerated statin dose, in combination with ezetimibe or in patients with statin intolerance, a PCSK9 inhibitor may be considered.
27 2016 ESC/EAS Guidelines for the management of dyslipidaemias Table of content: - What is cardiovascular disease prevention? - Total cardiovascular risk - Evaluation of laboratory lipid and apolipoprotein parameters - Treatment targets - Lifestyle modifications to improve the plasma lipid profile - Drugs for treatment of hypercholesterolaemia - Drugs for treatment of hypertriglyceridaemia - Drugs affecting high-density lipoprotein-cholesterol - Management of dyslipidaemia in different clinical settings - Monitoring of lipids and enzymes in patients on lipid-lowering therapy - Strategies to encourage adoption of healthy lifestyle changes and adherence to lipid modifying therapies
Treatment of dyslipidaemia in older adults Recommendations Class Level Treatment with statins is recommended for older adults with established CVD in the same way as for younger patients. I A Since older people often have co-morbidities and have altered pharmacokinetics, lipidlowering medication should be started at a lower dose and then titrated with caution to achieve target lipid levels that are the same as in younger subjects. IIa C Statin therapy should be considered in older adults free from CVD, particularly in the presence of hypertension, smoking, diabetes and dyslipidaemia. IIa B
Management of dyslipidaemia in women Statin treatment is recommended for primary prevention of CAD in high-risk women. Statins are recommended for secondary prevention in women with the same indications and targets as in men. Lipid-lowering drugs should not be given when pregnancy is planned, during pregnancy or during the breastfeeding period. However, bile acid sequestrants (which are not absorbed) may be considered.
Lipid management in patients with moderate to severe chronic kidney disease Recommendations Class Level Patients with stage 3 5 CKD have to be considered at high or very high CV risk. I A The use of statins or statin/ezetimibe combination is indicated in patients with nondialysis-dependent CKD. In patients with dialysis-dependent CKD and free of atherosclerotic CVD, statins should not be initiated. I III A A In patients already on statins, ezetimibe or on a statin/ezetimibe combination at the time of dialysis initiation, these drugs should be continued particularly in patients with CVD. IIa C In adult kidney transplant recipients treatment with statins may be considered. IIb C
Tips to aid adherence to multiple drug therapies 1. Agree on rather than dictate a drug regimen to your patient and tailor it to his/her personal lifestyle and needs. 2. Back up verbal instructions with clear written instructions. 3. Simplify the dosing regimen and consider a fixed dose combination pill where available. 4. Perform a regular review of medicines to minimize polypharmacy (or ask the pharmacist to assist). 5. Encourage self-monitoring and use cues and technologies to act as reminders. 6. Provide information on common side effects and discuss management strategies. 7. Involve the partner, other family members or the caregiver in the patient s treatment.