Mikhailidis Lipid Guidelines

8/19/2019 Mikhailidis Lipid Guidelines

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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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• 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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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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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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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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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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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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4] Some conditions (e.g. rheumatoid arthritis) that are accepteby other guidelines are only mentioned in parenthesis in the AC


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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.

Mikhailidis Lipid Guidelines

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