LIPID MANAGEMENT ACCORDING TO

2016 ESC/EAS GUIDELINES

dr. Erwin Mulia, SpJP(K), FAsCC, FIHA

Routine Assessment of Plasma
Lipid Profiles:
Total Cholesterol, LDL-C, HDL-C,
TG
Laboratory Methods for Evaluating LDL-
C

Method Recommendation

Friedewald TG < 400 mg/dL (fasting required)

• TG < 600 mg/dL (fasting not

required)
Direct
• Very high risk patients (ASCVD,
DM)

Erwinanto, et al. Panduan Tata Laksana

Dislipidemia. 2017
 Primary target: LDL-C

 Secondary target:
non-HDL-C (TC – HDL-
C)

 Not a target: HDL-C

 Steps To Achieve
Primary And Secondary
Lipid Targets
 STEP 1

Perform Risk
Assessment
 Risk Level
• Very High risk
– Known CVD
– Diabetes with TOD such as microalbuminuria or a major
risk factor: smoking, hypertension, dyslipidemia
– Severe CKD (GFR <30mL/min/1.73m2)
– A calculated 10 year risk SCORE ≥10%
• High risk
– Markedly elevated single risk factors e.g. familial
dyslipidaemias or severe hypertension.
– Most people with diabetes
– Moderate CKD (GFR 30-59mL/min/1.73m2)
– A calculated SCORE ≥5% and <10% for 10-year risk of
fatal CVD
• Moderate risk
– A calculated SCORE of ≥1% and <5% for 10-year risk of
fatal CVD
• Low risk
Catapano AL, et al. Eur Heart J.
2016;37:2999-3058
– The low risk category applies to individuals with SCORE
 Definition of CVD
 Unequivocally documented CVD on imaging
such as significant plaque on coronary
angiography or carotid ultrasound
 Myocardial infarction
 Acute coronary syndrome
 Coronary intervention (PCI)
 CABG and other arterial revascularization
procedures
 Stroke and TIA
Catapano AL, et al. Eur Heart J.
 Peripheral arterial disease (PAD)
2016;37:2999-3058
 CHD Risk Assessment
Based On SCORE System
 Variable of the SCORE Chart
 Gender
 Age
 Systolic Blood Pressure
 Total Cholesterol
 HDL-C
 Smoking

Catapano AL, et al. Eur Heart J.

2016;37:2999-3058
 High CVD Low CVD

Reiner Z, et al. Eur Heart J.

2011;32:1769-1818
Reiner et al; Management of Dyslipidemia - ESC Pocket
Guidelines
 STEP 2

Identify LDL-C Goal

 Treatment Targets of LDL-C
Risk Category LDL-C
Low and < 115 mg/dL

Moderate Risk (< 190 mg/dL and < 100

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
Catapano AL, et al. Eur Heart J.
2016;37:2999-3058
70-135 mg/dL
 STEP 3

Make a Strategy
to Reach LDL-C Goal
 Initiation of Treatment
LDL – C (mg/dL)
Total CV
Risk
100 – 155 –
(SCORE) % <70 70 – <100
<155 <190
≥190

LSI, drug
No No No No
if
<1 interventi interventi interventi interventi
uncontroll
on on on on
ed

LSI, drug LSI, drug LSI, drug

No No
if if if
≥1 – <5 interventi interventi
uncontroll uncontroll uncontroll
on on
ed ed ed

LSI, drug
>5 – <10 No LSI + LSI + LSI +
if
interventi
LSI = Lifestyle Intervention drug drug drug
or high risk uncontroll
onInfarction, statin therapy should therapy
*In patients wih Myocardial therapyof total cholesterol
be considered irrespective therapy
ed
levels
Catapano AL, et al. Eur Heart J.
2016;37:2999-3058
≥10 LSI, drug
LSI + LSI + LSI + LSI +
Strategy for LOW and MODERATE
risk patients

Visit 1 6 weeks Visit 2

Check lipid profile LDL goal not achieved
Start LSI Intensify LSI

6 weeks

Visit 3 Visit 3
LDL goal achieved LDL goal not achieved
Continue LSI Drug therapy

Monitor adherence every 4-6

months
 Lifestyle Interventions aimed to:
Lower LDL-C Increase HDL-C Lower TG

Reduce dietary saturated fat

Increase dietary fiber

Reduce total amount of dietary carbohydrate

Reduce alcohol intake

Increase habitual physical activity

Reduce excessive body weight

Quit smoking

Reiner Z, et al. Eur Heart J.

2011;32:1769-1818
 Drug Treatment
Risk Level Drug
Low Statin
Moderate Statin
Statin or Statin +
High
Ezetimibe
Very High Statin or Statin +
(no ASCVD or DM) Ezetimibe
Very High Statin or Statin +
(ASCVD or DM with Ezetimibe
TOD or or Statin + PCSK9
Major RF) Inhibitor
 Strategy to Reach LDL-C Goal
Risk level

Very high without

Low or moderate High
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

Uptitrate to
YES On maximally NO
maximally
tolerated high intensity
tolerated dose
statin?

NO NO
At LDL-C Ezetimibe 10 mg At LDL-C goal?
YES goal? should be considered (<70 mg/dL) YES
(<70 mg/dL)
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
Moderate-
High-intensity Low-intensity
intensity
statin therapy statin therapy
statin therapy
(mg) (mg)
(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 by approx. <30%
<50%
Atorvastatin 40-80 Atorvastatin 10-20 Simvastatin 10
Rosuvastatin 20- Rosuvastatin 5-10 Pravastatin 10-20
40 Simvastatin 20-40 Lovastatin 20
Pravastatin 40-80 Fluvastatin 20-40
Lovastatin 40 Pitavastatin 1
Fluvastatin Xl 80
Fluvastatin 40 bid
Pitavastatin 2-4
Donald M. Lloyd-Jones DM, et al. JACC. 2016;68:92-125
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
 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

LDL-C is above target
target
• Immediate fibrate
therapy regardless
of current LDL-C TLC and statin TLC and statin
level and CHD risk therapy 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
Catapano AL, et al. Eur Heart J.
specific reasons for more frequent reviews)
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
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
Symptoms improve:
persist: 1) Low-dose third
statin re- second statin at usual 1) Low-dose second
or starting dose efficacious (potent)++
challenge efficacious++ statin
statin
2) Efficacious++ statin with
Symptom- 2) Efficacious++ statin with
Sympto alternate day or
free: alternate day or
ms once/twice weekly
continue once/twice weekly
re-occur dosing regimen
statin dosing regimen

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

Ezetimibe

A + bile acid absorption

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

 First step: do risk assessment

 Second step: identify LDL-C goal based

on risk assessment

 Third step: make strategy to reach LDL-C

goal

 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
Lipid Workshop Case
A 60-year old gentleman visit your
office for consulting his lipid profile.

• He was hypertensive, controlled with

antihypertensive drugs
• Not a smoker
• Not aware of diabetes
• No family history of CAD
• History of heart attack, 1 year ago
• Dyslipidemic, being treated with
Physical examination:
• Blood pressure 120/80 mmHg.
• Other physical findings are non-remarkable.

Lipid profile:
• Total Cholesterol 219 mg/dL,
• LDL-C 130 mg/dL,
• HDL-C 38 mg/dL,
• Triglyceride 180 mg/dL.

Fasting blood glucose and liver enzymes are

within normal limits.
Chest x-ray normal, ECG shows old anteroseptal
wall MI.
What will you do first?

Identify LDL-C target

Start statin therapy

Start statin plus fenofibrate therapy

Perform risk assessment

GO TO STEP 1 OF LECTURE 2

PERFORM RISK
ASSESSMENT
 Risk Level
• Very High risk
– Known CVD
– Diabetes with TOD such as microalbuminuria or a major
risk factor: smoking, hypertension, dyslipidemia
– Severe CKD (GFR <30mL/min/1.73m2)
– A calculated 10 year risk SCORE ≥10%
• High risk
– Markedly elevated single risk factors e.g. familial
dyslipidaemias or severe hypertension.
– Most people with diabetes
– Moderate CKD (GFR 30-59mL/min/1.73m2)
– A calculated SCORE ≥5% and <10% for 10-year risk of
fatal CVD
• Moderate risk
– A calculated SCORE of ≥1% and <5% for 10-year risk of
fatal CVD
• Low risk
Catapano AL, et al. Eur Heart J.
2016;37:2999-3058
– The low risk category applies to individuals with SCORE
 Variable of the SCORE Chart
 Gender
 Age
 Systolic Blood Pressure
 Total Cholesterol
 HDL-C
 Smoking

Catapano AL, et al. Eur Heart J.

2016;37:2999-3058
 Definition of CVD
 Unequivocally documented CVD on imaging
such as significant plaque on coronary
angiography or carotid ultrasound
 Myocardial infarction
 Acute coronary syndrome
 Coronary intervention (PCI)
 CABG and other arterial revascularization
procedures
 Stroke and TIA
Catapano AL, et al. Eur Heart J.
 Peripheral arterial disease (PAD)
2016;37:2999-3058
What is the LDL-C target?

< 70 mg/dL

< 100 mg/dL

< 130 mg/dL

< 160 mg/dL

GO TO STEP 2 OF LECTURE 2

IDENTIFY LDL-C GOAL

LDL-C 130 mg/dL

Treatment Targets of LDL-C

Risk Category LDL-C
Low and < 115 mg/dL

Moderate Risk (< 190 mg/dL and < 100 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

Catapano AL, et al. Eur Heart J.

2016;37:2999-3058
Appropriate therapy for this
patient would be:
TLC (Therapeutic Lifestyle
Changes)
TLC + statin

TLC + statin + ezetimibe

TLC + statin + fibrate

TLC + statin + niacin

STEP 3 OF LECTURE 2

MAKE A STRATEGY

TO REACH LDL-C GOAL

 Initiation of Treatment
LDL – C (mg/dL)
Total CV
Risk
100 – 155 –
(SCORE) % <70 70 – <100
<155 <190
≥190

LSI, drug
No No No No
if
<1 interventi interventi interventi interventi
uncontroll
on on on on
ed

LSI, drug LSI, drug LSI, drug

No No
if if if
≥1 – <5 interventi interventi
uncontroll uncontroll uncontroll
on on
ed ed ed

LSI, drug
>5 – <10 No LSI + LSI + LSI +
LSI = Lifestyle Intervention interventi
if
drug drug drug
or high risk
*In patients wih Myocardial on
uncontroll
Infarction, statin therapy should betherapy therapy
considered irrespective therapy
of total cholesterol
levels
ed
Catapano AL, et al. Eur Heart J.
2016;37:2999-3058
≥10 LSI, drug
LSI + LSI + LSI + LSI +
 Lifestyle Interventions aimed to:
Lower LDL-C Increase HDL-C Lower TG

Reduce dietary saturated fat

Increase dietary fiber

Reduce total amount of dietary carbohydrate

Reduce alcohol intake

Increase habitual physical activity

Reduce excessive body weight

Quit smoking

Reiner Z, et al. Eur Heart J.

2011;32:1769-1818
 Drug Treatment
Risk Level Drug
Low Statin
Moderate Statin
Statin or Statin +
High
Ezetimibe
Very High Statin or Statin +
(no ASCVD or DM) Ezetimibe
Very High Statin or Statin +
(ASCVD or DM with Ezetimibe
TOD or or Statin + PCSK9
Major RF) Inhibitor
 High, Moderate, and Low-Intensity
Statin Therapy
Moderate-
High-intensity Low-intensity
intensity
statin therapy statin therapy
statin therapy
(mg) (mg)
(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 by approx. <30%
<50%
Atorvastatin 40-80 Atorvastatin 10-20 Simvastatin 10
Rosuvastatin 20- Rosuvastatin 5-10 Pravastatin 10-20
40 Simvastatin 20-40 Lovastatin 20
Pravastatin 40-80 Fluvastatin 20-40
Lovastatin 40 Pitavastatin 1
Fluvastatin Xl 80
Fluvastatin 40 bid
Pitavastatin 2-4
Donald M. Lloyd-Jones DM, et al. JACC. 2016;68:92-125
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
 STEP 4 OF LECTURE 2
ACHIEVE SECONDARY TARGET IN
HIGH AND VERY HIGH RISK PATIENTS
• Triglyceride 180
mg/dL.
TG ≥ 200 mg/dL

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

risk of CHD

Yes No

• TLC LDL-C is above

LDL-C is above target
target
• Immediate fibrate
therapy regardless
of current LDL-C TLC and statin TLC and statin
level and CHD risk therapy 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 OF LECTURE 2
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?
–AL,Annually
Catapano et al. Eur Heart J. (if there is no adherence problems or other

specific reasons for more frequent reviews)

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

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

Ezetimibe

A + bile acid absorption

A+B
inhibitor B + fibrate (not
gemfibrozil)
+: such as atorvastatin or
rosuvastatin
* Reiner Z et al. (2011) If still not at goal: consider additional (future) novel
Catapano AL, et al. Eur Heart J. therapies:
2016;37:2999-3058 PCSK9 monoclonal antibody therapy, CETP inhibitor