This document summarizes updates in hyperlipidemia management. It discusses how atherosclerosis is a chronic disease that starts early, and greater LDL-C exposure accelerates coronary heart disease risk. Lowering LDL-C goals are recommended across cardiovascular risk categories, with more intensive reduction compared to previous guidelines. PCSK9 inhibitors like evolocumab are effective and safe at lowering LDL-C and reducing cardiovascular events, even at very low LDL-C levels below previous targets.

1. Update in hyperlipidaemia management
Dr Adel Sallam.MD ,FCMR.FCCT
Cardiologist and advanced cardiovascular image
specialist

2. Atherosclerosis is a Chronic Disease and Starts Early
Coronary Calcium Carotid IMT IVUS NIR Spectroscopy
Coronary CT MR Angiography IVUS-VH OCT

3. Greater LDL-C Exposure Accelerates
CHD Risk1
0
Age in years
Cumulative
LDL-C
(g)
Threshold for CHD
60
3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57
0
80
60
40
20
Increased threshold age
Female sex
Decreased threshold age
Male sex
Smoking
Hypertension
Diabetes
↑TG, ↑Lp(a), ↓HDL-C
12.5 years 35 years 55 years
HoFH HeFH Without FH
CHD = coronary heart disease; FH = familial hypercholesterolemia; HeFH = Heterozygous Familial Hypercholesterolemia;
HDL-C = high density lipoprotein cholesterol; HoFH = Homozygous Familial Hypercholesterolemia; LDL-C = low-density
lipoprotein cholesterol; Lp(a) = lipoprotein(a); TG = triglycerides.
1- Nordestgaard BG, et al. Eur Heart J. 2013;34:3478-3490.

4. Lower LDL-C is Better:
Over 25 Years of Lipid Lowering Trials Consistently
Demonstrate1,2
1. The Cholesterol Treatment Trialists’ Collaboration. Lancet. 2010;376:1670-1681. 2. Raymond C, et al. Clev Clin J Med. 2014; 81:11-19.
2. Adapted from Raymond et al.2
Event
rate
(%)
Mean treatment LDL-C level at follow-up (mg/dL)
25%
20%
15%
10%
5%
0%
0 20 40 60 80 100 120 140 160 180 200
4S-pbo
LIPID-pbo
4S-Rx
LIPID-Rx
Every 40mg/dl, 1 mmol/dl decrease in LDL-C decreases relative risk of CV events by 20-25%1
MIRACL-pbo
HPS-pbo
CARE-pbo
CARE-Rx
HPS-Rx
A to Z-S20
A to Z-S40-80
MIRACL-Atv80
IDEAL-Atv80
IDEAL-Sim20-40
TNT-Atv10
PROVE-IT-Prv40
TNT-Atv80
PROVE-IT-Atv80

5. Cumulative
Effect of
Lifelong LDL-C
Log-Linear Effect of Lower LDL-C on CHD
Cannon CP, et al. AHA, November, 17 2014.
Ference, BA et al. J Am Coll Cardiol 2015;doi:10.1016/j.jacc.2015.02.020).

6. MEDICAL HISTORY
• BMI: 34 kg/m2
• Diagnosed three vessel coronary
artery disease 1n 2014
• Underwent CAG plus PCI twice (total
10 stent)
• Hypertension
• Diabetes
• Previous heavy smoker
KA lives a sedentary lifestyle and doesn’t
exercise regularly. His coronary risk factor
profile includes a smoker 30-year history of
cigarette smoking and altered lipid levels.
CURRENT TREATMENT REGIMEN
 Rosuvastatin 40 mg qd
 Valsartan 160 mg qd[
 Aspirin 81 mg qd
 Sitagliptin 50/1000 BID
Current Lipid Profile (mg/dL)
LDL-C 269
HDL-C 38
Triglycerides 120
Total Cholesterol 320
K A; 43 years

8. LDL Goal < 1.5 mmol/L in High Risk Patients

9. Unmet Needs in LDL-C Lowering: When Statins Won’t
Do1
. 1-Arafah M, Al-Hinai AT, Mahmeed WA, Al-Rasadi K, Tamimi OA, Herz SA et al. Centralized pan-middle east survey on the under
treatment of hypercholesterolemia: Results from the cepheus study in arabian gulf countries. Angiology. 2014; 65 (10): 919-926.
PR-REP-SAU-000040 JAN 2018

10. While Intensifying Statin Therapy Provides
Additional CV Risk Reduction, Residual CV Risk
Remains*
Residual Risk
Relative Risk Reduction
with Treatment
0.0
0.05
0.10
0.15
Major
Cardiovascular
Event
(%)
0 1 2 3 4 5 6
Years
Low Intensity Statin
High Intensity Statin
* LaRosa JC, et al. N Engl J Med. 2005;352:1425-1435.
A total of A total of 10,001
patients with coronary heart
disease and LDL-C of < 130
mg/dL were randomly
assigned to either low
intensity or high intensity
statin therapy.
*The primary endpoint was
the occurrence of a first
major cardiovascular event,
defined as death from CHD,
nonfatal non-procedure
related MI, resuscitation
after cardiac
arrest, or fatal or nonfatal
stroke.

11. MEDICAL HISTORY
• BMI: 34 kg/m2
• Diagnosed three vessel coronary
artery disease 2014
• Underwent CAG plus PCI twice (total
10 stent) 2ed attack 2016
• Hypertension
• Diabetes
• Previous heavy smoker
KA lives a sedentary lifestyle and doesn’t
exercise regularly. His coronary risk factor
profile includes a smoker 30-year history of
cigarette smoking and altered lipid levels.
CURRENT TREATMENT REGIMEN
 Rosuvastatin 40 mg qd
 Ezetimibe 10 mg qd
 Omacor 1g TID
 Valsartan 160 mg qd[
 Aspirin 81 mg qd
 Sitagliptin 50/1000 BID
Current Lipid Profile (mg/dL)
LDL-C 201
HDL-C 44
Triglycerides 115
Total Cholesterol 225
K A; 43 years

13. CV RISK CATEGORIES
2019 2016
1. ASCVD definition more precise
2. DM definition more precise
• T1DM of long durationadded
3. FH with ASCVD or another risk factoradded

14. CV RISK CATEGORIES 2019
2019 2016

15. • Trials of LDL-lowering indicate RELATIVE RISK reduction is proportional
to the ABSOLUTE REDUCTION in LDL-C
• Lower is better: lowering LDL-C with statins, ezetimibe, or PCSK9-
inhibitors safe and effective to <1.4 mmol/L (55mg/dL)
• Intensity of LDL-lowering therapy should be based on:
• (A) Risk, irrespective of cause(s) of the risk (e.g., primary or
secondary prevention, diabetes, or chronic kidney disease)
AND
• (B) baseline LDL cholesterol (which determines how much
reduction in risk can be achieved)
 FUNDAMENTAL PRINCIPLES FOR LDL LOWERING THERAPY
2019 ESC/EASGuidelinesfor the managementof dyslipidaemias: lipidmodification to reducecardiovascularrisk (EuropeanHeartJournal2019 -doi:10.1093/eurheartj/ehz455)

16. RECOMMENDED TREATMENT GOALS FOR LDL-LOWERING
THERAPY : MAIN CHANGES FROM 2016 to 2019
Riskcategory LDL goals (starting with untreated LDL-C)
2016 2019
<1.8mmol/L(70mg/dL)
or>50%ifLDL-C1.8-3.5
(70-135mg/dL)
<2.6mmol/L(100mg/dL)
or>50% ifLDL-C2.6-5.2
(100-200mg/dL)
<3.0 mmol/L (115 mg/dL)
<3.0 mmol/L (115 mg/dL)
<1.4 mmol/L (55 mg/dL)
and>50%↓
<1.8 mmol/L (70 mg/dL)
and>50%↓
< 2.6 mmol/L (100 mg/dL)
<3.0 mmol/L (115 mg/dL)
Very-high-risk
High-risk
Low-risk
1. MORE INTENSIVE REDUCTION OF LDL-C ACROSS CV RISK CATEGORIES
1 A
1 A
A
A
IIb
IIa
1
B
Moderate-risk
IIa C
B
B
1

20. The Role of PCSK9 in the Regulation of LDL Receptor
Expression

21. HR 0.85 (0.79-0.92)
P<0.0001
HR 0.80 (0.73-0.88)
P<0.0001
FOURIER: Effects of PCSK9i Evolocumab
27,564 high-risk, stable patients with established CV disease (prior MI, prior stroke, or
symptomatic PAD) + high risk feature
(2.6)
(2.07)
(1.5)
Placebo
59% reduction
P<0.00001
Absolute  56 mg/dl
15
10
(1.03)
Evolocumab
(median 30 mg/dl, IQR 19-46 mg/dl)
(0.52)
CVD, cardiovascular disease; cor revasc, coronary revascularization; KM, Kaplam-Meier; UA, unstable angina
5
0
CVD, MI, stroke
CVD, MI, stroke
UA, cor revasc
Sabatine MS et al. N Engl J Med. 2017; 376: 1713-22.
LDL-C
mg/dL
(mmol/L)
KM
rate
at
3
years
(%)

22. FOURIER – Lower CV Event Rates with Lower
LDL-C Levels*, Even Down to 20 mg/dL (0.52 mmol/L)
19.3 38.6 58 77.3 19.3 96.7 135.3 154.7 174
mmol/L
mg/dL
LDL cholesterol 4 weeks after randomisation
*Relationship between the achieved LDL-cholesterol concentration at 4 weeks and the risk of CVD, MI, or stroke
Giugliano RP et al. Lancet. 2017;390(10106):1962-1971.

23. FOURIER - Safety Events
% pts
25
20
15
10
5
Adj P-values for trend >0.10
for each comparison
LDL-C (mM) at 4 wks
<0.5
0.5-1.3
1.3-1.8
1.8-2.6
≥2.6
0
SAE AE->Discon New DM Cancer Cataract
SAE, serious adverse event;
DM, diabetes mellitus
Giugliano RP, et al.Presented at the European Society of Cardiology Congress, Barcelona, August 2017
Giugliano RP, et al. Lancet 2017 doi: /10.1016/S0140-6736(17)32290-0 [epub ahead of print]

24. FOURIER - Safety Events
% pts
10
% Patients (n/N)
LDL-C (mM) at 4 wks
<0.5
0.5-1.3
5
Adj P-values for trend >0.10
for each comparison
1.3-1.8
1.8-2.6
≥2.6
0
Neurocog AST/ALT↑ CK↑ Non-CV death Hem stroke
Giugliano RP, et al.Presented at the European Society of Cardiology Congress, Barcelona, August 2017
Giugliano RP, et al. Lancet 2017 doi: /10.1016/S0140-6736(17)32290-0 [epub ahead of print]

25. CV
Death,
MI,
or
Stroke
Benefit of EvoMab Based on
Time from Qualifying MI
Qualifying MI <2 yrs ago Qualifying MI ≥2 yrs ago
12% 12%
24% RRR 10.8% 13% RRR
10%
8%
HR 0.76
(95% CI 0.64-0.89)
P<0.001
Δ 2.9%
NNT 35
7.9%
10%
8%
HR 0.87
(95% CI 0.76-0.99)
P=0.04
9.3%
8.3%
Δ 1.0%
NNT 101
6%
4%
Placebo 6%
4%
Evolocumab
2%
Pinteraction=0.18
2%
0%
0 6 12 18 24 30 36
0%
0 6 12 18 24 30 36
Months after Randomization
Sabatine MS. Presented at the American Heart Association Scientific Sessions, Anaheim, November 2017

26. CV
Death,
MI,
or
Stroke
Benefit of EvoMab Based on #
of Prior MIs
≥2 Prior MIs 1 Prior MI
16% 16%
14%
12%
10%
21% RRR
HR 0.79
(95% CI 0.67-0.94)
P=0.006
15.0%
Δ 2.6%
NNT 38
12.4%
14%
12%
10%
16% RRR
HR 0.84
(95% CI 0.74-0.96)
P=0.008
8%
6%
4%
2%
0%
Placebo
Evolocumab
0 6 12 18 24 30 36
8%
6%
4%
2%
Pinteraction=0.57
0%
8.2%
6.6%
0 6 12 18 24 30 36
Δ 1.7%
NNT 60
Months after Randomization
Sabatine MS. Presented at the American Heart Association Scientific Sessions, Anaheim, November 2017

27. CV
Death,
MI,
or
Stroke
Benefit of EvoMab Based on
Multivessel Disease
Multivessel Disease No Multivessel Disease
14% 14%
12%
10%
8%
30% RRR
HR 0.70
(95% CI 0.58-0.84)
P<0.001
Placebo
12.6%
Δ 3.4%
NNT 29
9.2%
12%
10%
8%
11% RRR
HR 0.89
(95% CI 0.79-1.00)
P=0.055
8.9%
7.6%
Δ 1.3%
NNT 78
6%
4%
2%
0%
Evolocumab
0 6 12 18 24 30 36
6%
4%
2%
Pinteraction=0.03
0%
0 6 12 18 24 30 36
Months after Randomization
Sabatine MS. Presented at the American Heart Association Scientific Sessions, Anaheim, November 2017

28. H
o
s
p
f
o
r
U
A
,
o
r
C
o
r
R
e
v
a
s
c
CV
Death,
MI,
Stroke,
rd
Effect of Evolocumab
on Primary Endpoint
18%
16%
14%
12%
10%
8%
Patients w/ Diabetes at Baseline
Hazard Ratio 0.83
(95% CI 0.75-0.93)
P=0.0008
Placebo
17.1%
14.4%
D 2.7%
NNT 37
18%
16%
14%
12%
10%
8%
Patients w/o Diabetes at Baseline
Hazard Ratio 0.87
(95% CI 0.79-0.96)
P=0.0052
13.0%
11.4%
D 1.6%
NNT 62
6%
4%
Evolocumab
6%
4%
2%
0%
Pinteraction=0.60
2%
0%
0 6 12 18 24 30 36 0 6 12 18 24 30 36
Months after Randomization
Sabatine MS. Presented at the European Association for the Study of Diabetes 53 annual meeting, Lisbon, September 2017

29. #
Events
1563 1344
1151
848
1st Even
t
HR 0.85
(0.65-0.85)
(0.79-0.92)
Additional
Events
RR 0.74
Total Primary Endpoint Events
Total Events
3000
2000
1000
0
RR 0.82
(95%CI 0.75-0.90)
2714
P<0.001
2192
Placebo Evolocumab
-522
-303
-219
Murphy AHA 2017

30. For patients with very high CV risk and ACS
For patients with very high CV risk and a recurrent ACS event
a
• Guidelines recommend initiation of high-intensity statin therapy in all statin-naïve
patients with ACS and no contraindications, regardless of baseline LDL-C levels•
Goal (class I recommendation ): ≥ 50% LDL-C reduction from baseline and
LDL-C < 1.4 mmol/L (< 55 mg/dL)
b
a
• Recurrent event is defined as another event within 2 years, while taking maximally
tolerated statin therapy
• Goal (class IIb recommendation ): LDL-C < 1.0 mmol/L (< 40 mg/dL)
a
b
For Patients with a Recurrent ACS Event,
a Lower LDL-C Goal should be Considered
Class I recommendations, the highest level recommendations in the guidelines, are based on evidence and/or general agreement that a given treatment is beneficial,
useful, and effective. Class IIb recommendations are those based on conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a given
treatment and the usefulness/efficacy is less well established by evidence/opinion than class IIa recommendations. Note that a primary prevention goal of ≥ 50% LDL-
C reduction from baseline and LDL-C < 1.4 mmol/L (< 55 mg/dL) for patients with FH at very high risk is a class IIa recommendation.
Second event does not necessarily need to be of the same type as the first event.
ACS, acute coronary syndrome; CV, cardiovascular; LDL-C, low-density lipoprotein cholesterol.
1. Mach F, et al. Eur Heart J. 2019. doi:10.1093/eurheartj/ehz455. [Epub ahead of print.].

31. 8 weeks
EVOPACS: Study Design Assessed Evolocumab in ACS
Patients within 24 - 72 Hours
ACS
(NSTEMI/UA,
STEMI)
N = 308
Randomized 1:1
1 country, 7 sites
In-hospital
(72 hours) Placebo SC QM + atorvastatin 40 mg QD (n = 153)
Evolocumab SC 420 mg QM + atorvastatin 40 mg QD (n = 155)
Assessments conducted day 1, weeks 4 and 8
PRIMARY ENDPOINT
 LDL-C change from baseline at week 8
INCLUSION CRITERIA
 ACS (NSTEMI/UA < 72H, STEMI < 24H)
SECONDARY ENDPOINT
 Safety and tolerability
 LDL-C levels
– ≥ 1.8 mmol/L (70 mg/dl) in patient previously on
stable treatment with high-intensity statin OR
– ≥ 2.3 mmol/L (90 mg/dl) in patients previously on
stable treatment with low- or moderate intensity statin
OR
– ≥ 3.2 mmol/L (125 mg/dL) in statin naïve patients or
patients not on stable statin treatment
ACS = acute coronary syndrome; SC = subcutaneous; QM = monthly; QD = daily; LDL-C = low-density lipoprotein cholesterol; NSTEMI = Non-ST-elevation myocardial infarction;
STEMI = ST-elevation myocardial infarction; UA = unstable angina; AE = adverse eventa
1. Koskinas KC, et al. Clinical Cardiology. 2018;41:1513-1520. 2. Koskinas KC, et al. JACC. [published online ahead of print August 31, 2019]. https://doi.org/10.1016/j.jacc.2019.08.010

32. Evolocumab
(n = 155)
Placebo
(n = 153)
Age (years)
Male gender, n (%)
)
Body mass index (kg/m2
Diabetes mellitus, n (%)
Insulin-treated
Arterial hypertension, n (%)
Active smoking, n (%)
Previous myocardial infarction, n (%)
Previous PCI, n (%)
Previous CABG, n (%)
Peripheral arterial disease, n (%)
History of stroke, n (%)
History of TIA, n (%)
History of malignancy, n (%)
In the evolocumab group, 15% of patients had a history of previous MI and
3% of patients had PAD
5 (3) 4 (3)
60.5±12.0 61.0±10.7
128 (83) 123 (80)
26.9±4.0 27.8±3.9
23 (15) 24 (16)
1 (1) 6 (4)
79 (51) 85 (56)
64 (41) 46 (30)
24 (15) 19 (12)
25 (16) 23 (15)
4 (3) 4 (3)
2 (1) 0 (0)
5 (3) 0 (0)
13 (8) 10 (7)
Baseline Demographics and CV Risk Factors
were Well Balanced
PCI = percutaneous coronary intervention; CABG = coronary artery bypass graft; TIA = trans ischemic attack; MI = myocardial infarction; PAD = peripheral artery disease
Koskinas KC, et al. JACC. [published online ahead of print August 31, 2019]. https://doi.org/10.1016/j.jacc.2019.08.010

33. Evolocumab
(n = 155)
Placebo
(n = 153)
a
Statin treatment , n (%)
No statin
Low- or moderate-intensity
statin
High-intensity statinb
Ezetimibe treatment, n (%)
124 (80) 117 (76)
13 (8) 22 (14)
18 (12) 14 (9)
6 (4) 9 (6)
a b
Majority of Patients Enrolled were Statin-Naïve
at Baseline
Stable (unchanged) in the past ≥4 weeks prior to study enrolment. Atorvastatin ≥40mg, rosuvastatin ≥20mg, or simvastatin 80mg.
Koskinas KC, et al. JACC. [published online ahead of print August 31, 2019]. https://doi.org/10.1016/j.jacc.2019.08.010

34. Calculated
LDL-
cholesterol
(mmol/L)
The reduction in LDL-C levels was evident at 4 weeks and maintained at 8 weeks
Primary Endpoint: Significant Reduction in LDL-C
at 8 Weeks
3.61 mmol/L
(139 mg/dL)
3.42 mmol/L
(132 mg/dL)
Mean Values (±SD)
2.00 mmol/L
(77 mg/dL)
0.79 mmol/L
(31 mg/dL)
2.06 mmol/L
(80 mg/dL)
0.79 mmol/L
(31 mg/dL)
No. of patients
Placebo
Evolocumab
148
146
144
136
149
141
Absolute difference, LS means (mmol/L) 1.34 1.43
Percentage difference 38.4% 40.7%
P-value <0.001 <0.001
AE, adverse event; LS = least-squares; LDL-C = low-density lipoprotein cholesterol; SD = standard deviation .
Koskinas KC, et al. JACC. [published online ahead of print August 31, 2019]. https://doi.org/10.1016/j.jacc.2019.08.010

35. Mean
Percentage
Change
From
Baseline
In
LDL-cholesterol
The percent change in LDL-C from baseline to week 8 was 77% in the
evolocumab group and 35% in the placebo group
Percent Change in LDL-C at 4 Weeks was
Maintained at Week 8
Placebo Evolocumab Placebo Evolocumab
P < 0.001 P < 0.001
AE, adverse event; LS = least-squares; LDL-C = low-density lipoprotein cholesterol; SD = standard deviation
Koskinas KC, et al. JACC. [published online ahead of print August 31, 2019]. https://doi.org/10.1016/j.jacc.2019.08.010

36. Proportion
of
patients
Proportion
of
patients
Compared with placebo, substantially more patients receiving evolocumab were able to
achieve LDL-C levels < 1.8 (96% vs 38%) and < 1.4 mmol/L (90% vs 11%)
90% of Evolocumab Patients Achieved New ESC/EAS
Guideline Goal of LDL-C < 1.4 mmol/L (< 55 mg/dL)
LDL-C < 1.8 mmol/L (<70 mg/dL) LDL-C < 1.4 mmol/L (<55 mg/dL)
Placebo Evolocumab Placebo Evolocumab
LDL-C = low-density lipoprotein cholesterol
Koskinas KC, et al. ESC 2019, Paris Aug 31-Sept 4.
Koskinas KC, et al. JACC. [published online ahead of print August 31, 2019]. https://doi.org/10.1016/j.jacc.2019.08.010
Mach F. et al. Eur J Heart. [published online ahead of print August 31, 2019]. https://doi.org/10.1093/eurheartj/ehz455

37. Evolocumab
(n = 155) a
Placebo
(n = 152)
P-value
Any adverse event
Serious adverse event
Adverse event resulting in study
drug discontinuation
The percentage of patients who experienced AEs, SAEs, and AEs
resulting in study discontinuation were similar between groups
78 (50.3) 77 (50.7) 0.72
12 (7.7) 11 (7.2) 0.84
2 (1.3) 3 (2.0) 0.65
a
Secondary Endpoint: No New Safety Findings
Number (proportion) of patients with each event type are reported, not counting multiple events of the same type. Fisher's exact tests in case of zero events in one group.
Excluded is one patient randomly allocated to placebo who withdrew consent early and refused study drug injection and any study intervention.
AE = adverse event; SAE = serious adverse event
Koskinas KC, et al. JACC. [published online ahead of print August 31, 2019]. https://doi.org/10.1016/j.jacc.2019.08.010

38. Summary
• The EVOPACS study demonstrated that evolocumab, in addition to high-intensity
statin therapy, resulted in significantly greater reduction in LDL-C levels after 8 weeks,
compared with high-intensity statin therapy alone
• Evolocumab was well tolerated, with no new safety findings
• Treatment with evolocumab in the ACS setting enabled:
– > 95% of patients to achieve LDL-C targets < 1.8 mmol/L (<70 mg/dL), compared
with 38% of patients receiving statin therapy alone
– > 90% of patients to achieve LDL-C targets < 1.4 mmol/L (<55 mg/dL), compared
with 11% of patients receiving statin therapy alone, which aligns with the LDL-C
goal in 2019 ESC/EAS Dyslipidemia Guidelines
LDL-C = low-density lipoprotein cholesterol
Koskinas KC, et al. ESC 2019, Paris Aug 31-Sept 4.
Koskinas KC, et al. JACC. [published online ahead of print August 31, 2019]. https://doi.org/10.1016/j.jacc.2019.08.010
Mach F, et al. Eur J Heart. [published online ahead of print August 31, 2019]. https://doi.org/10.1093/eurheartj/ehz455

40. NEW LOWER TARGET FOR THOSE AT
HIGHEST RISK

41. The Role of PCSK9 Mabs in New Guidelines

42. Assess risk and titrate to risk
Here is how

43. a
Addition of a PCSK9 Inhibitor Received
the Highest Class I Recommendation for
Very High Risk Secondary Prevention and FH Patients
Recommendation
Class of
recommendationa
For primary prevention patients at very high risk, but without FH, who do not achieve their
LDL-C goal on a maximally tolerated dose of statin and ezetimibe, combination with a
PCSK9 inhibitor may be considered
IIb
For very-high-risk secondary prevention patients not achieving their goal on
a maximally tolerated dose of statin and ezetimibe, combination with a PCSK9
inhibitor is recommended
I
For very high risk FH patients (i.e. with ASCVD or another major risk factor) who
do not achieve their goal on a maximally tolerated dose of statin and ezetimibe,
combination with a PCSK9 inhibitor is recommended
I
If a statin-based regimen is not tolerated at any dosage (even after rechallenge), a
PCSK9 inhibitor added to ezetimibe may also be considered
IIb
Class I recommendations, the highest level recommendations in the guidelines, are based on evidence and/or general agreement that a given treatment is beneficial, useful, and
effective. Class IIb recommendations are those based on conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a given treatment and the
usefulness/efficacy is less well established by evidence/opinion than class IIa recommendations.
ASCVD, atherosclerotic cardiovascular disease; FH, familial hypercholesterolaemia; LDL-C, low-density lipoprotein cholesterol; PCSK9, proprotein convertase subtilisin/kexin type 9.
1. Mach F, et al. Eur Heart J. 2019. doi:10.1093/eurheartj/ehz455. [Epub ahead of print.].

44. Patients unable to
tolerate statins
Difficult to Treat Hyperlipidaemia
PCSK9 Inhibitors
Evolocumab, Alirocumab
Patients with Familial
Hypercholesterolemia
(i.e HoFH & HeFH)
Very high Lp(a)
Hypercholesterolemia in
patients at VERY HIGH CV
risk (not at LDL-C goal with
max tolerated statin±Eze)
PCSK9 Inhibitors: Challenging Hyperlipidemia
CURRENT LIPID LOWERING STRATEGIES (Statins±Ezetimibe) Targeting
LDL-C
C
LDL-C
Very high LDL-C
plasma levels
Very low LDL-C goal
In Very high CV risk

45. MEDICAL HISTORY
• BMI: 32 kg/m2
• Diagnosed with severe coronary
artery
disease with a three vessel coronary
artery disease
• Underwent CAG plus PCI twice (total
10 stent)
• Hypertension
• Diabetes
• Previous heavy smoker
With life style modification
exercise regularly.
cigarette smoking and marked improve
lipid levels.
CURRENT TREATMENT REGIMEN
 Evolocumab 140 mg Q2w
 Rosuvastatin 40 mg qd
 Ezetimibe 10 mg qd
 Omacor 1g TID
 Valsartan 160 mg qd[
 Aspirin 81 mg qd
 Sitagliptin 50/1000 BID
Current Lipid Profile (mg/dL)
LDL-C 25
HDL-C 41
Triglycerides 97
Total Cholesterol 111
K A; 43 years

49. Conclusions
• Clinical care starts with an assessment of absolute risk
• E.G. Very HIGH risk (secondary Prevention) or Very High Risk Primary
Prevention- Reduce LDL-C by 50%
and
• THEN titrate LDL-C to risk
• First Optmise Statins (High Intensity) then Ezetimibe
• PCSK9 inhibitors can be added any oral regimen when there is
insufficient LDL-C reduction in a patient for their level of risk
• ACHIEVE THE LDL THAT IS RIGHT FOR YOUR PATIENT
20