LIPID GUIDELINES: 2015

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)

DECLARATION OF INTEREST
Attended conferences and gave talks sponsored
by MSD and Genzyme

DECLARATION OF INTEREST
Lead: Guidelines for Medical Management of
Carotid Artery Stenosis (Eur Soc Vasc Surg)
Chairperson: Expert Panel on Small Dense
Low Density Lipoprotein
Co-chairperson: Expert Panel on Post-Prandial
Hypertriglyceridaemia

DECLARATION OF INTEREST
Editor-in-Chief of several journals, including:
Curr Med Res Opin
Expert Opin Pharmacother
Angiology
Curr Vasc Pharmacol
Open Cardiovasc Med J

American College of Cardiology (ACC) and American Heart Association

(AHA) guidelines
November 2013
Stone, N. J. et al. 2013 ACC/AHA guideline on the treatment of blood
cholesterol to reduce atherosclerotic cardiovascular risk in adults: a
report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines. Circulation
http://dx.doi.org/10.1161/01.cir.0000437738.63853.7a.

 ACC/AHA 2013: Mention the use of statins almost exclusively. Risk

calculation and threshold controversial. Rejected by the EAS, IAS, NLA
and ADA. They are statin guidelines, not lipid guidelines.
IAS guidelines 2013: Mention the use of bile acid sequestrants or
ezetimibe for patients not getting to LDL-C target or unable to tolerate a
high dose statin or any statin dose.
National Institute for Clinical Excellence (NICE) 2014: Similar to IAS, EAS.

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 patients
UK JBS2 (2005) 2.0 mmol/l (80 mg/dl) (total
cholesterol 4.0 mmol/l; 160 mg/dl)
European (2007) 2.5 mmol/l (96 mg/dl)
Canada (2009) 2.0 mmol/l (80 mg/dl)
ESC/EAS (2011) 1.8 mmol/l (70 mg/dl)

ACC/AHA GUIDELINES 2013

1] A new pooled equation to calculate risk.
This equation seems to overestimate risk leading to more patients being
treated with statins. We should consider that the cost effectiveness of such
an initiative, if very low risk patients are treated, may be offset by new onset
diabetes (NOD) and other adverse effects (e.g. cataracts) associated with
statin use.
Aspirin analogy
Healthy volunteer effect
Who will be (over)calculated as high risk?
Limited to USA population

ACC/AHA GUIDELINES 2013

1] A new pooled equation to calculate risk.

This threshold for intervention is set at 7.5%. The authors maintain that
there is evidence even at 5%! They state that it is reasonable to consider
moderate intensity statin therapy at a risk of 5 7.5%.

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

ACC/AHA GUIDELINES 2013

2] No specific low density lipoprotein cholesterol (LDL-C) targets. Instead the
percentage reduction in LDL-C in different risk categories is specified. For
example, high-intensity statin therapy, that lowers LDL-C by 50%, is
recommended mainly for secondary prevention and in some patients with
diabetes.
Do you leave a high risk patient who has an LDL-C at target without drug
administration? Do you lower and LDL-C of 2.6 to 1.3 mmol/l (100 to 50
mg/dl)?

ACC/AHA GUIDELINES 2013

3] There is no guidance regarding the use of non-statin lipid lowering drugs.
The International Atherosclerosis Society (IAS) 2013 position paper specifies
that these drugs (e.g. ezetimibe and bile acid sequestrants) can be used in
addition to statins or in statin intolerant patients.
The NICE guidelines (2014) also specify the same as the IAS guidelines and
focus on atorvastatin as first choice statin.

Hypertension example do we have trials for every combination we use?

SHARP trial for ezetimibe? IMPROVE-IT trial?

ACC/AHA GUIDELINES 2013

4] Some conditions (e.g. rheumatoid arthritis) that are accepted as high risk
by other guidelines are only mentioned in parenthesis in the ACC/AHA text.

ACC/AHA GUIDELINES 2013

5] No follow up checks needed.
GFR decline with age and risk of hypothyroidism? Unrecognised drug
interactions? NAFLD/NASH?

CHD EQUIVALENTS

Diabetes
Peripheral arterial disease
Symptomatic carotid disease
Abdominal aortic aneurysm
Chronic kidney disease (eGFR <60 ml/min/1.73m2
Rheumatoid arthritis (?psoriasis + arthritis, SLE)

Potential CHD Equivalents

Non-Alcoholic Fatty Liver Disease (NAFLD), especially NASH (NonAlcoholic Steatohepatitis)
Metabolic Syndrome, Impaired Fasting Glucose, Impaired Glucose Tolerance
Obstructive Sleep Apnoea (OSAS)
Erectile Dysfunction (ED)
Periodontitis
Chemotherapy (e.g. anthracyclines) and Radiotherapy (chest)

Inflammatory Bowel Disease

Jafri H, Alsheikh-Ali AA, Karas RH. Meta-analysis: statin therapy does

not alter the association between low levels of high-density lipoprotein
cholesterol and increased cardiovascular risk. Ann Intern Med 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 in
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 control
participants, respectively.

TG LEVELS AND VASCULAR

DISEASE
Risk of vascular events was increased in a metaanalysis of 262,525 participants (10,158 events).
Increase in risk was in the range of 19 27% for every
1.0 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

TG LEVELS AND VASCULAR

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)

Whatever the guidelines shared decisionmaking framework is the way forward

SUMMARY

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?

Athyros VG, Katsiki N, Karagiannis A, Mikhailidis DP. The 2013 American

College of Cardiology/American Heart Association guidelines for the treatment of
dyslipidemia: mind the gaps! Curr Med Res Opin 2014;30:1701-5.
Mikhailidis DP, Athyros VG. Dyslipidaemia in 2013: New statin guidelines and
promising novel therapeutics. Nat Rev Cardiol 2014;11:72-4.