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8/19/2019 Mikhailidis Lipid Guidelines
1/23
LIPID GUIDELINES: 2 15
D P Mikhailidis
BSc MSc MD FCPP FCP FRSPH FFPM FRCP FRCPath
Academic Head
Dept. of Clinical Biochemistry
(Vascular Disease Prevention Clinics)
Royal Free campus
University College London (UCL)
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DECLARATION OF INTEREST
• Attended conferences and gave talks sponsor
by MSD and Genzyme
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DECLARATION OF INTEREST
• Lead: Guidelines for Medical Management o
Carotid Artery Stenosis (Eur Soc Vasc Surg )
• Chairperson: Expert Panel on Small Dense
Low Density Lipoprotein
• Co-chairperson: Expert Panel on Post-Prand
Hypertriglyceridaemia
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DECLARATION OF INTEREST
Editor-in-Chief of several journals, includi
• Curr Med Res Opin
• Expert Opin Pharmacother
• Angiology
• Curr Vasc Pharmacol
• Open Cardiovasc Med J
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American College of Cardiology ACC) and American Heart A
AHA) guidelines
November 2013
Stone, N. J. et al. 2013 ACC/AHA guideline on the treatment ocholesterol to reduce atherosclerotic cardiovascular risk in adreport of the American College of Cardiology/American HeartAssociation Task Force on Practice Guidelines. Circulation http://dx.doi.org/10.1161/01.cir.0000437738.63853.7a.
http://dx.doi.org/10.1161/01.cir.0000437738.63853.7ahttp://dx.doi.org/10.1161/01.cir.0000437738.63853.7a
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• ACC/AHA 2013: Mention the use of statins almost exclusivelycalculation and threshold controversial. “Rejected” by the EAand ADA. They are “statin” guidelines, not lipid guidelines.
• IAS guidelines 2013: Mention the use of bile acid sequestrantezetimibe for patients not getting to LDL-C target or unable tohigh dose statin or any statin dose.
• National Institute for Clinical Excellence (NICE) 2014: Similar t
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GUIDELINE LDL TARGETS
USA (2001) ≤ 2.6 mmol/l ( 100 mg/dl)
UK (2004) ≤ 2.0 mmol/l ( 80 mg/dl)USA (2004) ≤ 1.8 mmol/l ( 70 mg/dl)(optional) very high risk patientsUK JBS2 (2005) ≤ 2.0 mmol/l ( 80 mg/d
cholesterol 4.0 mmol/l; 160 mg/dl)European (2007) ≤ 2.5 mmol/l ( 96 mg/Canada (2009) ≤ 2.0 mmol/l ( 80 mg/d
ESC/EAS (2011) ≤ 1.8 mmol/l (70 mg/
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ACC/AHA GUIDELINES 2013
1] A new pooled equation to calculate risk.
This equation seems to overestimate risk leading to more patietreated with statins. We should consider that the cost effectivean initiative, if very low risk patients are treated, may be offsetdiabetes (NOD) and other adverse effects (e.g. cataracts) assocstatin use.
Aspirin analogy
“Healthy volunteer effect”
Who will be (over)calculated as high risk?
Limited to USA population
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ACC/AHA GUIDELINES 2013
1] A new pooled equation to calculate risk.
This threshold for intervention is set at 7.5%. The authors mainthere is evidence even at 5%! They state that it is reasonable tomoderate intensity statin therapy at a risk of 5 – 7.5%.
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ACC/AHA GUIDELINES 2013
1] A new pooled equation to calculate risk.
Vaucher et al. Eur Heart J 2014:35: 958-59
Ray K et al. Eur Heart J 2014:35: 960-68
Ridker PM, Cook NR. Lancet 2013; 382:1762-65
Seth B et al. Metabolism 2014; in press
Banerjee S et al. Expert Rev Cardiovasc Ther 2014; 12: 285-90
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ACC/AHA GUIDELINES 2013
2] No specific low density lipoprotein cholesterol (LDL-C) targetpercentage reduction in LDL-C in different risk categories is speexample, high-intensity statin therapy, that lowers LDL-C by ≥50recommended mainly for secondary prevention and in some padiabetes.
Do you leave a high risk patient who has an LDL-C at target witadministration? Do you lower and LDL-C of 2.6 to 1.3 mmol/l (1mg/dl)?
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ACC/AHA GUIDELINES 2013
3] There is no guidance regarding the use of non-statin lipid lowThe International Atherosclerosis Society (IAS) 2013 position pathat these drugs (e.g. ezetimibe and bile acid sequestrants) canaddition to statins or in statin intolerant patients.
The NICE guidelines (2014) also specify the same as the IAS guidfocus on atorvastatin as first choice statin.
Hypertension example – do we have trials for every combinatio
SHARP trial for ezetimibe? IMPROVE-IT trial?
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ACC/AHA GUIDELINES 2013
4] Some conditions (e.g. rheumatoid arthritis) that are accepteby other guidelines are only mentioned in parenthesis in the AC
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ACC/AHA GUIDELINES 2013
5] No follow up checks needed.
GFR decline with age and risk of hypothyroidism? Unrecognisedinteractions? NAFLD/NASH?
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CHD EQUIVALENTS
•
Diabetes• Peripheral arter ial disease
• Symptomatic carotid disease
• Abdominal aortic aneurysm• Chronic kidney disease (eGFR
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Potential CHD Equivalents
• Non-A lcoholic Fatty L iver Di sease (NAFLD), especially NASH (Non-
Alcoholic Steatohepatitis)
• Metabolic Syndrome, Impaired Fasting Glucose, Impaired Glucose Tole
• Obstructive Sleep Apnoea (OSAS)
• Erectile Dysfunction (ED)
• Periodontitis
• Chemotherapy (e.g. anthracyclines) and Radiotherapy (chest)
• I nf lammatory Bowel Di sease
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Jafri H, Alsheikh-Ali AA, Karas RH. Meta-analysis: statin therapy d
not alter the association between low levels of high-density lipoprotei
cholesterol and increased cardiovascular risk. Ann I ntern M ed 2010
21;153:800-8
20 RCTs: 543 210 person-years of follow-up; 7 838 MIs
After adjustment for on-treatment LDL-C levels, age, hypertension,
diabetes, and tobacco use, there was a significant inverse association
between HDL-C levels and risk for MI in statin-treated patients and
control participants.
In Poisson meta-regressions, every 0.26 mmol/L (10 mg/dL) decrease
HDL-C was associated with 7.1 (95% CI 6.8 - 7.3) and 8.3 (8.1 - 8.5)
more MIs per 1000 person-years in statin-treated patients and contro
participants, respectively.
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TG LEVELS AND VASCULA
DISEASE
Risk of vascular events was increased in a meta-
analysis of 262,525 participants (10,158 events).
Increase in risk was in the range of 19 – 27% for eve1.0 mmol/l (88 mg/dl) increase in TG levels from the
baseline value after a follow up of 4 – 12 years.
N Sarwar et al. Circulation 2007; 115: 450-8
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TG LEVELS AND VASCULA
DISEASE
Links with:
HDL (inverse relationship; quality of HDL?)
LDL (dense LDL – more atherogenic)
Coagulation (e.g. factor VII)
Insulin resistance (e.g. metabolic syndrome,
IFG, IGT, DM)
Obesity (NAFLD and vascular risk)
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Whatever the guidelines “shared dec
making framework” is the way forw
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SUMMARY
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1] Who to treat:
Calculating risk; CHD equivalents; risk engines
2] Targets:Absolute levels vs % fall of LDL-C
3] What to use to achieve targets:
Statins and what else? PSCK-9?
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Athyros VG, Katsiki N, Karagiannis A, Mikhailidis DP. The 2013 Ameri
College of Cardiology/American Heart Association guidelines for the tre
dyslipidemia: mind the gaps! Curr Med Res Opin 2014;30:1701-5.
Mikhailidis DP, Athyros VG. Dyslipidaemia in 2013: New statin guidelin promising novel therapeutics. Nat Rev Cardiol 2014;11:72-4.
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