History of dyslipidemia guideline development

2016 2017

ESC/EAS guideline Update ESC/EAS task force

PERKI
• Risk assessment
• SCORE chart PCSK9 inhibitor

European Heart Journal (2016) 37, 2999–3058

European Heart Journal (2017) 0, 1–13
 STEP 1

Perform Risk Assessment

Risk categories

European Heart Journal (2016) 37, 2999–3058

 STEP 2

Identify LDL-C Goal

 Treatment Goals for LDL-C
Risk Category LDL-C

Low and Moderate Risk < 115 mg/dL

High Risk < 100 mg/dL

or ≥ 50%  if baseline 100-200 mg/dL

Very High Risk < 70 mg/dL

or ≥ 50%  if baseline 70-135 mg/dL
 STEP 3

Make a Strategy
to Reach LDL-C Goal
Strategy for LOW and MODERATE risk patients
 Drug Treatment
Risk Level Drug
Low Statin

Moderate Statin

High Statin or Statin + Ezetimibe

Very High
Statin or Statin + Ezetimibe
(no ASCVD or DM)
Very High Statin or Statin + Ezetimibe
(ASCVD or DM with TOD or
Major RF) or Statin + PCSK9 Inhibitor
 Strategy to Reach LDL-C Goal
Risk level

Low or moderate High Very high without

ASCVD or DM
% LDL-C reduction
to target?

Choose appropriate Moderate to high High intensity

intensity statin* intensity statin statin

LDL-C target not achieved LDL-C target not achieved LDL-C target not achieved

Up titrate statin dose High intensity statin High intensity statin +

or or ezetimibe
Higher intensity statin High intensity statin +
ezetimibe

*Mostly low to moderate intensity

 Strategy for ASCVD and Diabetes
Patients at very high CV risk i.e.
• Documented ASCVD, clinical or unequivocal on imaging
• Diabetes and TOD with major RF

YES On maximally NO Uptitrate to maximally

tolerated high intensity tolerated dose
statin?

NO NO
At LDL-C goal? Ezetimibe 10 mg At LDL-C goal?
YES (<70 mg/dL) should be considered (<70 mg/dL) YES

LDL-C Rapid
NO >140 mg/dL? progression of NO
(requiring >50% reduction ASCVD and LDL-C
to reach goal) >100 mg/dL

YES

Consider PCSK9 inhibitor treatment to attain LDL-C goal (<70 mg/dL)

Chapman MJ, et al. Eur Heart J. 2016.

doi:10.1093/eurheartj/ehw480
High, Moderate, and Low-Intensity Statin Therapy

High-intensity Moderate-intensity Low-intensity

statin therapy (mg) statin therapy (mg) statin therapy (mg)

Daily dose lowers Daily dose lowers Daily dose lowers

LDL-C on average, LDL-C on average, LDL-C on average,
by approx. ≥50% by approx. 30% to <50% by approx. <30%
Atorvastatin 40-80 Atorvastatin 10-20 Simvastatin 10
Rosuvastatin 20-40 Rosuvastatin 5-10 Pravastatin 10-20
Simvastatin 20-40 Lovastatin 20
Pravastatin 40-80 Fluvastatin 20-40
Lovastatin 40 Pitavastatin 1
Fluvastatin Xl 80
Fluvastatin 40 bid
Pitavastatin 2-4
LDL-C Reduction With Each Titration of
Rosuvastatin, Atorvastatin, Simvastatin, or
Pravastatin

Rosuvastatin (mg) Atorvastatin (mg) Simvastatin (mg) Pravastatin (mg)

Mean %
Change
in LDL-C
From
Untreated
Baseline

p<0.002 vs atorvastatin 10 mg; simvastatin 10, 20, 40 mg; †p<0.002 vs atorvastatin 20, 40
mg; simvastatin 20, 40, 80 mg; pravastatin 20, 40 mg; ‡ p<0.002 vs atorvastatin 40 mg;
simvastatin 40, 80 mg; pravastatin 40 mg
Jones PH et al. Am J Cardiol.. 2003;92:152–160
 Efficacy of Combination of Ezetimibe and
Statins in Lowering LDL-C

RSV, rosuvastatin; EZE, ezetimibe; SIM, simvastatin

a p = 0.002 vs. SIM 40 mg/EZE 10 mg,
b p < 0.001 vs. SIM 40 mg/EZE 10 mg and SIM 80 mg/EZE 10 mg,

Ballantyne CM, et al. Atherosclerosis.. 2014;232:86–93.

 Long Term Follow-Up Statin
Treatment

B Death from Cardiovascular Causes A CHD-Related Death or Nonfatal MI

12 20

Placebo Placebo
10
16

8
Participants with Event (%)

Participants with Event (%)

12
6 Pravastatin Pravastatin
8
4 P<0.001
P=0.01 4
2

0 0
0 2 4 6 8 10 12 14 16 0 2 4 6 8 10 12 14 16
Years since Randomization Years since Randomization
No. at Risk No. at Risk

Placebo 3293 3254 3185 3113 3022 2902 2785 2114 Placebo 3293 3199 3071 2953 2841 2691 2549 1903
Pravastatin 3302 3275 3223 3158 3068 2974 2835 2177 Pravastatin 3302 3237 3157 3065 2943 2819 2675 2026

Ford I, et.al. N Eng J Med. 2007; 357:1477-

86
 STEP 4

Achieve Secondary Target in

high and very high risk patients
 TG ≥ 200 mg/dL

TG ≥ 500 mg/dL High or very high 10-year risk of CHD

Yes No

• TLC LDL-C is above target LDL-C is above target

• Immediate fibrate therapy

regardless of current LDL-C
level and CHD risk TLC and statin therapy TLC and statin therapy

LDL-C target is achieved but

TG is stil ≥ 200mg/dL

Consider fenofibrate addition

 Non-HDL-C is apo-B containing lipoprotein
(IDL, VLDL, and LDL)

Non-HDL-C = TC - HDL

Non-HDL-C target is 30 mg/dL above LDL-C target

 STEP 5

Monitoring of lipids and

enzymes in patients on lipid-
lowering therapy
 Testing Lipids
How often should lipids be tested?
– Before starting lipid-lowering drug treatment, at least 2
measurements with an interval of 1-12 weeks, EXCEPT in
conditions where concomitant drug treatment is suggested such
as ACS and very high-risk patients

How often should a patient’s lipids be tested after starting lipid-

lowering treatment?
– 8 (±4) weeks after starting treatment
– 8 (±4) weeks after adjustment of treatment until within the
target range

How often should lipids be tested once a patient has reached the
target or optimal lipid level?
– Annually (if there is no adherence problems or other specific
reasons for more frequent reviews)
Catapano AL, et al. Eur Heart J. 2016;37:2999-
3058
 Monitoring Liver Enzymes
How often should liver enzymes (SGPT) be routinely measured in
patients on lipid-lowering drugs?
– Before treatment
– Once 8-12 weeks after starting a drug treatment or after dose
increase
– Routine control of SGPT thereafter is not recommended during
lipid-lowering treatment
What if liver enzymes become elevated in a person taking lipid-
lowering drugs?
If SGPT<3x ULN:
– Continue therapy.
– Recheck liver enzymes in 4-6 weeks
If value rises ≥3x ULN:
– Stop lipid-lowering therapy or reduce dose and recheck liver
enzymes within 4-6 weeks.
– Cautious reintroduction of therapy may be considered after
SGPT has returned to normal.
– If SGPT remains elevated check for other reasons
Catapano AL, et al. Eur Heart J. 2016;37:2999-
3058
 Consider if Statin-Attributed Muscle Symptoms
Favour Statin Continuation/Reinitiation

Symptomatic & CK <4x ULN CK ≥4x ULN +/- rhabdomyolisis

2-4 weeks washout of statin 6 weeks washout of statin until

normalisation of CK: creatinine and
symptoms

Symptoms improve:
Symptoms persist:
second statin at usual or
statin re-challenge 1) Low-dose third efficacious 1) Low-dose second
starting dose
(potent)+ statin efficacious+ statin
2) Efficacious+ statin with 2) Efficacious+ statin with
Symptom-free: Symptoms alternate day or once/twice alternate day or once/twice
continue statin re-occur weekly dosing regimen weekly dosing regimen

Aim: achieve LDL-C goal* with maximally tolerated dose of statin

Ezetimibe

A + bile acid absorption inhibitor A+B

B + fibrate (not gemfibrozil)

+: such as atorvastatin or rosuvastatin

* Reiner Z et al. (2011) If still not at goal: consider additional (future) novel therapies:
PCSK9 monoclonal antibody therapy, CETP inhibitor
Catapano AL, et al. Eur Heart J. 2016;37:2999-
3058
SUMMARY
STEPS IN MANAGING DYSLIPIDEMIA

q First step: do risk assessment

q Second step: identify LDL-C goal based on risk

assessment

q Third step: make strategy to reach LDL-C goal

q Fourth step: treat non-HDL-C in high and very high risk

patients in whom LDL-C target has been achieved but
non-HDL-C is still 30 mg/dl above LDL-C targets

q Fifth step: monitor lipids and enzymes