CV Heart Talk Series

Dyslipidemia Management: New

Guidelines & Total Vascular
Benefit
Rizaldy Pinzon, MD, PhD
Bethesda Hospital/ Duta Wacana University School of Medicine
Yogyakarta
PP-LIP-IDN-0090-JAN-2021
Core Principles of
Dyslipidemia Management:
Guideline, Treatment Targets, Lipid-
lowering Therapy
Case
• J is a 60-year-old female with a history of dyslipidemia, hypertension and type II
diabetes mellitus.
• For the last month, the patient had been experiencing numbness and tingling in
her left great toe.
• Her blood pressure was elevated at 148/98, but the remainder of her vital signs
were all within normal range.
• The patient reported that her home blood glucose readings had been 150-200
mg/dL.
• The patient’s mother, father, and brother had a history of coronary artery disease.
Case
• The patient was currently taking 500 mg of metformin, 81 mg of aspirin, 20
mg of lisinopril, 20 mg of atorvastatin and one tablet of a multivitamin daily.
• Her HbA1c was elevated at 7.8%,
• Her total cholesterol was high at 220 mg/dL, triglycerides were also
elevated at 186 mg/dL, her LDL was 110 mg/dL, and her HDL was low at 36
mg/dL.
• The patient’s medication was adjusted as follows, her atorvastatin was
increased to 40 mg every evening, lisinopril was also increased to 40 mg
daily, and her metformin will be slowly titrated to reach 1,000 mg twice
daily.
Quiz
• Which is recommended by the American Diabetes Association regarding the use
of statins in patients with type 2 diabetes?
A. Moderate-intensity statins are recommended in all patients with type 2 diabetes
and CVD
B. High-intensity statins are recommended in all patients with type 2 diabetes
regardless of the level of glycemic control
C. High-intensity statins are only recommended in patients who have a history of
myocardial infarction
D. Moderate-intensity statins are recommended in all patients with type 2 diabetes
40-75 years of age without CVD or who are not at high risk for CVD
 Age and the impact of LDL-C on atherosclerosis
Greater RRR per Lesser RRR
mmol/l reduction Plaque stabilisation Response to initiation of LDL lowering
Plaque resolution

Fatty streaks Complex plaque

Artery wall
LDL chol (mmol/l)

FH LDLc rise with age (men)

Polygenic HC
Integrated LDL exposure

Age (years)
FH, familial hypercholesterolemia; HC, hypercholesterolemia; LDL-C, low-density lipoprotein cholesterol; RRR, relative risk reduction.
Packard CJ. Trends Cardiovasc Med 2018;28:348-354.
 ESC/EAS 2019 recommendations for risk assessment
• Risk factor screening including the lipid profile should be considered in men >40 years old and in women
>50 years of age or postmenopausal

• SCORE (Systematic Coronary Risk Evaluation) scheme should be used to estimate the 10-year risk of a first
fatal CV event, such as a stroke or heart attack, or cardiac sudden death

• No risk estimation model is needed in patients already at high or very high risk such as those with:
documented ASCVD, type 1 or type 2 diabetes, very high levels of individual risk factors, familial
hypercholesterolemia, carotid plaque, or chronic kidney disease

New recommendations for risk assessment include:

 ApoB analysis
 Measurement of Lp(a) at least once in each person’s lifetime
 Arterial ultrasound or coronary artery calcium score to refine risk estimation in
selected moderate-risk or low-risk patients
ACS, acute coronary syndrome; ApoB, apolipoprotein B; ASCVD, atherosclerotic cardiovascular disease; CAC, coronary artery calcium; CV, cardiovascular; CVD, cardiovascular disease; DM, diabetes mellitus; FH, familial hypercholesterolemia; HDL, high-
density lipoprotein; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein(a); T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; TGs, triglycerides.
Mach, F. et al. Eur Heart J.2020 Jan 1;41(1):111-188
2019 ESC/EAS Guidelines: CV risk categories
VERY HIGH-RISK HIGH-RISK MODERATE-RISK LOW-RISK
• Documented ASCVD* • TC >8 mmol/L (>310 • Young patients (type 1 • Calculated SCORE <1% for
• Diabetes mellitus† mg/dL); LDL-C >4.9 diabetes mellitus <35 years; 10-year risk of fatal CVD
• Severe CKD‡ mmol/L (>190 type 2 diabetes mellitus <50
• Very high levels of mg/dL); BP ≥180/110 years) with disease duration
individual risk factors§ mmHg <10 years, without other risk
• Diabetes mellitusǁ factors
• Moderate CKD¶ • Calculated SCORE ≥1% and
<5% for 10-year risk of fatal
CVD

*Documented ASCVD, either clinical or unequivocal on imaging. Documented ASCVD includes previous ACS (MI or unstable angina), stable angina, coronary revascularization, stroke and TIA, and peripheral arterial disease. Unequivocally documented
ASCVD on imaging includes those findings that are known to be predictive of clinical events, such as significant plaque on coronary angiography or CT scan (multivessel coronary disease with two major epicardial arteries having >50% stenosis), or on
carotid ultrasound.
†
Diabetes mellitus with target organ damage, or at least three major risk factors, or early onset of type 1 diabetes mellitus of long duration (>20 years).
‡
eGFR <30 mL/min/1.73 m 2.
§
A calculated SCORE ≥10% for 10-year risk of fatal CVD; FH with ASCVD or with another major risk factor.
ǁ
Diabetes mellitus without target organ damage, with diabetes mellitus duration ≥10 years or another additional risk factor.
¶
eGFR 30-59 mL/min/1.73 m 2.
ASCVD, atherosclerotic cardiovascular disease; BP: blood pressure; CKD, chronic kidney disease; CV, cardiovascular; CVD, cardiovascular disease; EAS, European Atherosclerosis Society; eGFR, estimated glomerular filtration rate; ESC, European Society
of Cardiology; LDL-C, low-density lipoprotein cholesterol; MI, myocardial infarction; SCORE, Systematic Coronary Risk Estimation; TC, total cholesterol.
Mach, F. et al. Eur Heart J.2020 Jan 1;41(1):111-188
AHA Cholesterol Guidelines 2018
Executive summary: Risk enhancers
In adults 40 to 75 years of age without diabetes mellitus and 10-year risk of 7.5% to 19.9%
(intermediate risk), risk-enhancing factors favour initiation of statin therapy 

• Family history of premature ASCVD

• Metabolic syndrome
• Chronic kidney disease
• History of preeclampsia or premature menopause (age <40 years)
• Chronic inflammatory disorders (eg, rheumatoid arthritis, psoriasis or chronic HIV)
• Apolipoprotein B ≥130 mg/dL, high-sensitivity C-reactive protein ≥2.0 mg/L,
• Ankle-brachial index (ABI) <0.9

Grundy SM, et al. Circulation 2019; 139:e1082-e1143.

ESC/EAS 2019 LDL-C: Goals for patients of different risk
levels
Risk Group New (2019) LDL-C goals Previous (2016) LDL-C goals

≥50% LDL reduction and

<1.4 mmol/L (<55 mg/dL)
<1.8 mmol/L (<70 mg/dL) or ≥50% ↓ if baseline
Very high including T2DM ASCVD + another event within
1.8–3.5 mmol/L (70–135 mg/dL)
2 years: consider LDL-C goal
<1.0 mmol/L (<40 mg/dL)

≥50% LDL reduction and <2.6 mmol/L (<100 mg/dL) or ≥50% ↓ if baseline
High including T2DM
<1.8 mmol/L (<70 mg/dL) 2.6–5.1 mmol/L (100–200 mg/dL)

Moderate <2.6 mmol/L (<100 mg/dL) <3.0 mmol/L (<115 mg/dL)

Low <3.0 mmol/L (<116 mg/dL) <3.0 mmol/L (<115 mg/dL)

ASCVD, atherosclerotic cardiovascular disease; CAC, coronary artery calcium;; CV, cardiovascular; CVD, cardiovascular disease; DM, diabetes mellitus; HDL, high-density lipoprotein; LDL-C, low-density lipoproteins cholesterol; Lp(a), lipoprotein(a);
PUFAs, polyunsaturated fatty acids; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus.
Mach, F. et al. Eur Heart J.2020 Jan 1;41(1):111-188
AHA Cholesterol Guidelines 2018:
Intervention algorithms Personalized approach
LDL-C ≥190 mg/dL (≥4.9 mmol/L): No risk assessment; High-intensity statin (Class I)
Primary prevention:
Access ASCVD risk in Diabetes mellitus and age 40-75 y: Moderate-intensity statin (Class I)
each age group
emphasize adherence Diabetes mellitus and age 40-75 y:
to healthy lifestyle Risk assessment to consider high-intensity statin (Class llia)
Age >75 y: Clinical assessment, risk discussion

Age 0–19 y Age 20–39 y Age 40–75 y

Lifestyle to prevent or reduce Estimate lifetime risk to encourage lifestyle to LDL-C ≥70-<190 mg/dL (≥1.8-4.9
ASCVD risk reduce ASCVD risk mmol/L) without diabetes mellitus
Diagnosis of familial Consider statin if family history premature 10-year ASCVD risk percent begins risk
hypercholesterolemia  statin ASCVD and LDL-C ≥160 mg/dL (≥4.1 mmol/L) discussion
Risk stratification
<5% 5%-<7.5% ≥7.5%-<20% ≥20%
“Low risk” “Borderline risk” “Intermediate risk” “High risk”

Risk discussion:
Risk discussion:
If risk enhancers present
Risk discussion: Patient preferences
If risk estimate + risk
Emphasize lifestyle to then risk discussion Risk discussion:
enhancers favor statin,
reduce risk factors regarding moderate- Initiate statin to reduce
initiate moderate-intensity
(Class I) intensity statin therapy LDL-C ≥50% (Class I)
statin to reduce LDL-C by
(Class IIb) 30%-49% (Class I)

Grundy SM, et al. Circulation 2019; 139:e1082-e1143.

Tailored regimen
LDL-C, Low density Lipoprotein-Cholesterol; ASCVD, Atherosclerotic Cardiovascular Disease, AHA: American Heart Association
 Age, cholesterol and CHD risk –
Predicted greater relative risk reduction with early intervention
A Age at risk (years): B
Age at risk Sex Number of
80–89 (years): deaths
Men 2919 0.79 (0.74–0.84)
80–89
Woman 2707 0.92 (0.86–0.97)
70–79 Total 5626 0.85 (0.82–0.89)
Test for heterogeneity: x21=12.0 (p=0.0005)
0.80 (0.77–0.83)
60–69 Men 7372
Hazard ratio (95% Cl)

70–79 0.86 (0.82–0.90)

Woman 3457
Total 10829 0.82 (0.80–0.85)
50–59 Test for heterogeneity: x21=4.1 (p=0.04)
0.71 (0.69–0.74)
60–69 Men 8594 0.73 (0.68–0.78)
Woman 1825 0.72 (0.69–0.74)
40–49 Total 10419
Test for heterogeneity: x21=0.3 (p=0.6)
0.59 (0.57–0.61)
50–59 Men 5001 0.55 (0.49–0.61)
Woman 560
Total 5561 0.58 (0.56–0.61)

Test for heterogeneity: x21=1.5 (p=0.2) 0.45 (0.41–0.48)

40–49 Men 1191 0.43 (0.34–0.55)
Woman 118
Total 1309 0.44 (0.42–0.48)

Test for heterogeneity: x21=0.0 (p=0.8)

Test for trend by age: x21=415 (p<0.0001)

Usual total cholesterol (1 mmol/L) Hazard ratio (95% Cl) for 1 mmol/L
Lower usual total cholesterol
Prospective Studies Collaboration Lancet 2007;370;1829-1839.
CHD, coronary heart disease; CI, confidence interval
Inherited vs pharmacologically based LDL lowering
2x2 factorial mendelian randomization study: log-linear association between genetically and
pharmacologically mediated lower low-density lipoprotein cholesterol and risk of coronary heart disease

‘Earlier is better’
Proportional risk reduction (SE) log

Genetic variants PCSK9 46L

LDL lowering from rs11591147
birth
NPC1L1 LDL-C score
HMGCR LDL-C score
scale

LDLR
rs2228671 LDLR LDL lowering trials
ABCG5/8 rs6511720 A to Z GISSI-P
rs4299376 PCSK9 Average age 62 yrs
rs11206510 Combined
HMGCR NPC1L1 & HMGCR LDL-C score
rs12916 ALLHAT-LLT
PCSK9
rs2479409 HMGCR LDL-C score
IMPROVE-IT
NPC1L1 NPC1L1 LDL-C score
SEARCH
rs217386

Lower LDL-C (mg/dl)

Ference BA, et al. J Am Coll Cardiol 2015;65:1552-1561.
 Association of LDL-C with CHD risk in statin trials
4S – Placebo
Rx - Statin therapy
PRA – pravastatin
ATV - atorvastatin
Secondary Prevention

4S – Rx
Event rate (%)

LIPID – Placebo

LIPID – Rx CARE – Placebo

CARE – Rx Primary Prevention
HPS – Rx TNT – ATV10 HPS – Placebo
TNT – ATV80 PROVE - IT – PRA WOSCOPS – Placebo
PROVE - IT – ATV AFCAPS – Placebo
AFCAPS – Rx WOSCOPS – Rx
JUPITER – RSV ASCOT – Placebo
JUPITER – Placebo
ASCOT – Rx

LDL-C achieved mg/dL (mmol/L)

1. Rosensen RS. Exp Opin Emerg Drugs 2004;9:269-279. 2. LaRosa JC, et al. N Engl J Med 2005;352:1425-1435.
 2019 ESC/EAS Guidelines: Treatment algorithm for
pharmacological LDL-C lowering
Total CV assessment
In selected low- and moderate-risk patients
Baseline LDL-C levels
Risk modifiers
imaging (subclinical atherosclerosis)
Y Indication for drug therapy N

Define treatment goal Lifestyle advice/ interventions

High potency statin at highest

recommended / tolerable dose to reach the • Secondary prevention (very high-risk)
goal Add PCSK9 • Primary prevention: patient with FH and
inhibitor another major risk factor (very-high risk)

Y LDL-C goal reached? N

N
Consider adding • Primary prevention: patients at
PCSK9 inhibitor very-high risk but without FH
Follow-up annually, or Add ezetimibe
more frequently if
indicated

LDL-C goal reached? Y Follow-up annually, or more frequently if indicated

ASCVD, atherosclerotic cardiovascular disease; BP, blood pressure; CKD, chronic kidney disease; CV, cardiovascular; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; FH, familial hypercholesterolemia; LDL-C, low-density lipoprotein cholesterol;
PCSK9, proprotein convertase subtilisin/kexin type 9; SCORE, Systematic Coronary Risk Estimation; T1DM, type 1 DM; T2DM, type 2 DM; TC, total cholesterol.
Mach, F. et al. Eur Heart J.2020 Jan 1;41(1):111-188
2019 ESC/EAS Guidelines: Sequence of therapies for
LDL-C lowering
• High-intensity statin to be prescribed up to the highest tolerated dose to reach treatment
goals
• If goals not achieved: add ezetimibe
• Consider/add PCSK9 inhibitor if:
• LDL-C goal is not achieved on maximum tolerated statin and ezetimibe in patients with very high
risk, without FH, for primary prevention
• LDL-C goal not achieved on maximum tolerated statin and ezetimibe in patients with very high risk
FH*
• If a statin-based regimen is not tolerated at any dosage (even after re-challenge), ezetimibe should be
considered
• If a statin-based regimen is not tolerated at any dosage (even after re-challenge), a PCSK9 inhibitor
added to ezetimibe may also be considered
• If the goal is not achieved, statin combination with a bile acid sequestrant may be considered
*With ASCVD or with another major risk factor.
ASCVD, atherosclerotic cardiovascular disease; FH, familial hypercholesterolemia; LDL-C, low-density lipoprotein cholesterol; PCSK9, proprotein convertase subtilisin/kexin type 9.
Mach, F. et al. Eur Heart J.2020 Jan 1;41(1):111-188
AHA Cholesterol Guidelines 2018
Executive summary – statin choice
In adults 40 to 75 years of age without diabetes mellitus and with LDL-C levels ≥70 mg/dL
(≥1.8 mmol/L), at a 10-year ASCVD risk of ≥7.5%, start a moderate-intensity statin if a discussion of
treatment options favours statin therapy 
High-, Moderate-, and Low-intensity Statin Therapy*
High intensity Moderate intensity Low intensity
LDL-C lowering ≥50% 30%–49% <30%
Statins Atorvastatin (40 mg) 80 mg Atorvastatin 10 mg (20 mg) Simvastatin 10 mg
Rosuvastatin 20 mg (40 mg) Rosuvastatin (5 mg) 10 mg
Simvastatin 20–40 mg
… Pravastatin 40 mg (80 mg) Pravastatin 10–20 mg
Lovastatin 40 mg (80 mg) Lovastatin 20 mg
Fluvastatin XL 80 mg Fluvastatin 20–40 mg
Fluvastatin 40 mg BID
Pitavastatin 1–4mg
Boldface type indicates specific statins and doses that were evaluated in RCTs, and the Cholesterol Treatment Trialists’ 2010 meta-analysis. All these RCTs
demonstrated a reduction in major cardiovascular events. 

Grundy SM, et al. Circulation 2019;139:e1082-e1143.

SPARCL: Assessing effect of atorvastatin on vascular
events by territory
BACKGROUND
In the SPARCL trial:
• Atorvastatin reduced the first occurrence of stroke and the first occurrence of a
composite of vascular events relative to placebo in patients with recent
stroke/TIA and no known CHD

The current post hoc analysis of SPARCL data aimed to determine the extent to which
atorvastatin may have reduced vascular events

SPARCL, Stroke Prevention by Aggressive Reduction in Cholesterol Levels. CHD, coronary heart disease; TIA, transient ischemic attack.
Szarek M, et al. J Am Coll Cardiol 2020;75:2110-2118.
Atorvastatin reduced first and total vascular events
Cerebrovascular Coronary Peripheral

-164
events
390 fewer total vascular events with
Number of vascular events

atorvastatin (1,218 events for placebo,

828 events for atorvastatin)

Reductions by atorvastatin were evident

-102 in each territory
events

-55 -69
events events

Atorvastatin Placebo Atorvastatin Placebo Atorvastatin Placebo Atorvastatin Placebo

First event Second event Third event Fourth and subsequent

events
Szarek M, et al. J Am Coll Cardiol 2020;75:2110-2118.
Atorvastatin reduced first and total vascular events
Cumulative incidence functions for first and total vascular events
Atorvastatin reduced:
• First vascular events by Total vascular: HR (95% Cl) 0.68 (0.60–0.77), p<0.001
First vascular: HR (95% Cl) 0.73 (0.66–0.82), p<0.001 Placebo
total vascular
27% (p<0.001)

Expected vascular events

per 100 participants
• Total vascular events by Atorvastatin
total vascular
32% (p<0.001) Placebo first
vascular

• Total vascular events by Atorvastatin

first vascular
10% during the first year
(p=0.19) and by 40% after
the first year (p<0.001)

Years since randomization

No. at risk
Placebo 2,366 2,301 2,255 2,192 2,139 1,009 159
Atorvastatin 2,365 2,287 2,229 2,176 2,123 1,028 140
Szarek M, et al. J Am Coll Cardiol 2020;75:2110-2118.
Atorvastatin reduced events in all vascular territories
Total events
[Events per 100 participants]*
Atorvastatin Placebo HR (95% CI) p-value
(n=2,365) (n=2,366)

Total vascular 828 [42.3] 1,218 [62.7] 0.68 (0.60–0.77) <0.001

Total cerebrovascular 571 [28.2] 748 [37.1] 0.76 (0.66–0.88) <0.001

Total coronary 203 [10.8] 373 [20.1] 0.54 (0.42–0.70) <0.001

Total peripheral 54 [2.8] 97 [4.8] 0.56 (0.35–0.89) 0.014

* 6 years after randomization

Atorvastatin Placebo
better better

Over 6 years, 20 vascular events/100 participants were avoided with atorvastatin treatment
Szarek M, et al. J Am Coll Cardiol 2020;75:2110-2118.
SPARCL Post-hoc analysis
Conclusions
After a recent stroke or TIA: the total number of vascular events prevented
with atorvastatin was more than twice the number of first events prevented
with significant reductions in total cerebrovascular, total coronary and total
peripheral events

Reduction in total events may be considered another comprehensive metric

reflecting the clinical benefit and efficiency of atorvastatin treatment in
reducing disease burden after stroke or TIA

SPARCL, Stroke Prevention by Aggressive Reduction in Cholesterol Levels; TIA, transient ischemic attack.

Szarek M, et al. J Am Coll Cardiol 2020;75:2110-2118.

TST (French cohort):
Evaluating benefit of targeting lower LDL-C levels
BACKGROUND
• SPARCL: 16% RRR with 5-year treatment with atorvastatin 80 mg/day vs placebo in patients with
stroke and no known CHD
• Based on SPARCL, the 2014 AHA/ASA and 2010 ESO guidelines recommended statin therapy
to lower lipid levels after TIA/ischemic stroke

• The TST trial evaluated the benefit of targeting an LDL-C <70 mg/dL to
reduce the risk of CV events in 2,860 patients with ischemic stroke with
atherosclerotic stenosis of cerebral vasculature, in French and Korean
populations
• The present analysis evaluates the French cohort of the TST trial
(5.3 years follow-up)
SPARCL, Stroke Prevention by Aggressive Reduction in Cholesterol Levels; TST, Treating Stroke to Target.
AHA/ASA, American Heart Association/American Stroke Association; CV, cardiovascular; ESO, European Stroke Organization; LDL-C, low-density lipoprotein cholesterol.
Amarenco P, et al. Stroke 2020;51:1231-1239.
Rate of primary endpoint was lower in patients with
LDL-C goal <70 mg/dL
Event rate, %

Primary endpoint: composite of ischemic

stroke; MI; new symptoms requiring urgent
coronary or carotid revascularization; and
vascular death

Strategy
Time, year
<70 mg/dL 1073 915 807 691 590 487 392 253 106
100±10 mg/dL 1075 889 800 702 586 475 353 238 104

Amarenco P, et al. Stroke 2020;51:1231-1239.

Targeting lower LDL-C significantly reduced the
primary endpoint
Primary endpoint: composite of ischemic stroke; MI; new symptoms requiring urgent coronary
or carotid revascularization; and vascular death

HR 0.74 (95% Cl 0.57–0.95);

12.9 p=0.019
Absolute risk reduction = 3.3%
NNT = 30
Patients (%)

9.6

<70 mg/dL
100±10 mg/dL

Primary endpoint
Amarenco P, et al. Stroke 2020;51:1231-1239.
Targeting lower LDL-C significantly reduced
vascular events
p=0.021
HR (95% CI) 0.75 (0.58–0.96)

p=0.023
HR (95% CI) 0.72 (0.54–0.96) 13.6
p=0.046
HR (95% CI) 0.73 (0.54–0.99)

10.4 10.3
Patients (%)

9.1
7.5
6.7

<70 mg/dL (N=1073)

100±10 mg/dL (N=1075)

Cerebral infarction/urgent carotid or All strokes Primary endpoint or intracranial

cerebral artery revascularization (Cerebral infarction or hemorrhage
intracranial hemorrhage)

Selected secondary outcomes

Amarenco P, et al. Stroke 2020;51:1231-1239.
TST (French cohort): Conclusion

After an ischemic stroke of documented atherosclerotic origin:

Targeting an LDL-C of <70 mg/dL during 5.3 years

prevented 1 subsequent major vascular event in 4
without increasing the risk of intracranial hemorrhage (NNT 30)

Amarenco P, et al. Stroke 2020;51:1231-1239.

2019 ESC/EAS Guidelines: Treatment of dyslipidemia in
patients with prior ischemic stroke

Lipid-lowering therapy for prevention of ASCVD events in patients with prior ischaemic stroke

Class Level
Patients with a history of ischaemic stroke or TIA are at very-high risk of
ASCVD, particularly recurrent ischaemic stroke, so it is recommended that
they receive intensive LDL-C-lowering therapy. I A

EAS, European Atherosclerosis Society; ESC, European Society of Cardiology; ASCVD, atherosclerotic cardiovascular disease; LDL-C, low-density lipoprotein cholesterol; TIA, transient ischemic attack.

Mach, F. et al. Eur Heart J.2020 Jan 1;41(1):111-188

Statin-specific Issues in
Dyslipidemia Management
2018 AHA/ACC Guidelines: Statin-associated side effects
The guideline “prefers statin-associated side effects because the large majority of patients are able to tolerate statin
rechallenge with an alternative statin or alternative regimen, such as reduced dose or in combination with non-statins”

Statin-associated side effects Frequency Predisposing factors

RCTs: 1-5% Age, female sex, low BMI, high-risk medications*, comorbidities#,
Myalgia (CK Normal) Observational studies/ Asian ancestry, excess alcohol, high levels of physical activity,
clinical setting: 5-10% and trauma

Myositis/myopathy (CK > ULN) with

Rare -
symptoms or objective weakness

Rhabdomyolysis Rare -
Statin-associated autoimmune myopathy Rare -

Depends on population; more

DM risk factors:
New-onset DM frequent if DM risk factors
BMI ≥30, FBG ≥100 mg/dL; metabolic syndrome, HbA1c ≥6%
are present

Transaminase elevation 3 x ULN Infrequent -

Hepatic failure Rare -

*High-risk medications: CYP3A4 inhibitors, OATP1B1 inhibitors. #Comorbidities: HIV, renal, liver, thyroid, preexisting myopathy.
BMI, body mass index; CK, creatine kinases; DM, diabetes mellitus; FBG, fasting blood glucose; HbA 1c, hemoglobin A1C; RCTs, randomized controlled trials; ULN, upper limit of normal.
Grundy SM, et al. J Am Coll Cardiol 2018:25709.
Myalgia occurred at a low and similar incidence in patients
receiving atorvastatin 10 mg and atorvastatin 80 mg
Incidence of myalgia with atorvastatin (Atv) 10 and 80 mg
compared with placebo (Pbo)

A retrospective analysis of pooled data from 49 clinical

trials of atorvastatin in 14,236 patients treated for an
average period of 2 weeks to 52 months

All cause
Treatment-associated

2.9 2.7

1.4 1.5
1.2 0.7
Atv 10 mg (n=7,258) Atv 80 mg (n=4,798) Pbo (n=2,180)

Newman C, et al. Am J Cardiol 2006;97:61-67.

Statin therapy in Asian diabetic patients:
Effects on renal function
Objective: To investigate and compare the statins affecting renal function in Asian patients with diabetes
Change in kidney function after statin use Change in lipid level after statin use

p=0.012 p<0.001 p<0.001

eGFR, ml/min/1.73m2

p=0.001

LDL-C, mg/dL
Atorvastatin Rosuvastatin Atorvastatin Rosuvastatin
Baseline 1 year Baseline 1 year

In both statin treatment groups, patients showed improved serum lipid levels and significantly reduced eGFRs

Conclusions: Moderate-intensity dose of atorvastatin was associated with fewer

detrimental effects on renal function than rosuvastatin
GFR, glomerular filtration rate; LDL-C, low-density lipoprotein cholesterol.
Han E, et al. Endocrinol Metab. 2017;32:274-280.
LIPITOR Abbreviated Product Information
DESCRIPTION: Atorvastatin tablets for oral administration contain 10, 20, 40, 80 mg atorvastatin.
INDICATIONS AND USAGE: Atorvastatin is indicated as an adjunct to diet for the reduction of elevated total-C, LDL-C, apo B, and TG in patients with primary hypercholesterolemia, combined (mixed)
hyperlipidemia, and heterozygous and homozygous familial hypercholesterolemia when response to diet and other non pharmacological measures are inadequate. Prevention of cardiovascular complications in
patients with hypertension (40 years or older) and dyslipidemia with at least 3 risk factors for future cardiovascular events, such as LVH, ECG abnormalities, NIDDM, peripheral vascular disease, post history of
cerebrovascular events including transient ischemic attack (TIA) ≥3 months previously, microalbuminuria/proteinuria, smoking (regular smoker within the last year of 20 cigarettes or cigars/week), TC/HDL – C
ratio ≥6, and history of coronary artery disease event in a first degree relative before age 55 (males) or 60 (women), atorvastatin is indicated to: Reduce the risk of fatal CHD and non-fatal MI, Reduce the risk of
stroke, Reduce the risk of revascularization procedures and angina pectoris. Pediatric Patients (10-17 years of age), Atorvastatin is indicated as an adjunct to diet to reduce total-C, LDL-C and apo-B levels in boys
and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: LDL-C remains ≥190 mg/dL or LDL-C
remains ≥160 mg/dL and: There is a positive family history of premature CVD or Two or more other CVD risk factors are present in the pediatric patient. CONTRAINDICATIONS: Hypersensitivity to any component
of this medication, active liver disease or unexplained persistent elevations of serum transaminases exceeding three times the upper limit of normal (ULN), or who are pregnant, breast-feeding, or of childbearing
potential who are not using adequate contraceptive measures. SPECIAL WARNINGS AND SPECIAL PRECAUTIONS FOR USE: Hepatic Effects: As with other lipid-lowering agents of the same class, moderate (>3 x
ULN) elevations of serum transaminases have been reported following therapy with atorvastatin. Skeletal Muscle Effect – Myalgia, has been reported in atorvastatin- treated patients. The risk of myopathy is
increased with concurrent administration of drugs that increase the systemic concentration of atorvastatin. Hemorrhagic stroke: Patients with hemorrhagic stroke on entry appeared to be at increased risk for
recurrent hemorrhagic stroke. INTERACTION WITH OTHER MEDICAMENTS AND OTHER FORMS OF INTERACTION: The risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with
concurrent administration of cyclosporine, fibric acid derivatives, lipid-modifying doses of niacin or CYP 3A4 inhibitors (e.g Erythromycin and azole antifungals). UNDESIRABLE EFFECT: The most frequent (more
than 1%) adverse effects associated with atorvastatin therapy, in patients participating in controlled clinical studies were dyspepsia, abdominal pain, headache, nausea, myalgia, asthenia, constipation, flatulence,
arthralgia, diarrhea, and insomnia. POSOLOGY AND METHOD OF ADMINISTRATION: The usual starting dose is 10 mg once a day. The dosage range is 10 to 80 mg once daily. Doses may be given any time of the
day with or without food. Starting and maintenance dosage should be individualized according to baseline LDL-C levels, the goal of therapy, and patient response. After initiation and/or upon titration of
atorvastatin, lipid levels should be analyzed within 2 to 4 weeks, and dosage adjusted accordingly. Primary Hypercholesterolemia and Combined (Mixed) Hyperlipidemia - The majority of patient are controlled with
10 mg atorvastatin once daily. A therapeutic response is evident within 2 weeks, and the maximum response is usually achieved within 4 weeks. The response is maintained during chronic therapy. Homozygous
familial Hypercholesterolemia -In a compassionate-use study of patient with homozygous familial hypercholesterolemia, most patient responded to 80 mg of atorvastatin. Heterozygous familial
hypercholesterolemia in pediatric patients (10-17 years of age) – The recommended starting dose of atorvastatin is 10 mg/day; the maximum recommended dose is 20 mg/day (doses greater than 20 mg have
not been studied in this patient population). Doses should be individualized according to the recommended goal of therapy. Adjustment should be made at intervals of 4 weeks or more. Use in Children - Treatment
experience in a pediatric population is limited to doses of atorvastatin up to 80 mg/day for one year in 8 patients with homozygous FH. No clinical or biochemical abnormalities were reported in these patients.
Use in Combination with Other Medicinal Compounds - In cases where co-administration of atorvastatin with cyclosporine, telaprevir, or the combination tipranavir/ritonavir is necessary, the dose of atorvastatin
should not exceed 10 mg. Use of atorvastatin is not recommended in patients taking letermovir co-administered with cyclosporine. Pharmacokinetic drug interactions that result in increased systemic
concentration of atorvastatin have also been noted with other human immunodeficiency virus (HIV) protease inhibitors (lopinavir/ritonavir, saquinavir/ritonavir, darunavir/ritonavir, fosamprenavir,
fosamprenavir/ritonavir and nelfinavir), hepatitis C (HCV) protease inhibitors (boceprevir, elbasvir/grazoprevir, simeprevir), clarithromycin, itraconazole, and letermovir. Caution should be used when co-prescribing
atorvastatin, and appropriate clinical assessment is recommended to ensure that the lowest dose of atorvastatin necessary is employed. PRESENTATIONS: Lipitor 10 mg: Box of 3 blisters of 10 tablets; Box of 9
blisters of 10 tablets Reg. No. DKI 9790700217 A1. Lipitor 20 mg: Box of 3 blisters of 10 tablets; Box of 9 blisters of 10 tablets Reg. No. DKI 9790700217 B1, Lipitor 40 mg: Box of 3 blisters of 10 tablets; Box of 9
blisters of 10 tablets Reg. No. DKI 9790700217 C1, Lipitor 80 mg: Box of 3 blister of 10 tablets; Box of 9 blister of 10 tablets Reg No. DKI1790700217D1. STORAGE: Store below 30°C. HARUS DENGAN RESEP
DOKTER / On Medical Prescription Only.
Full product information can be requested to:
Reference: Latest BPOM Approved Lipitor Local Product Document 2021 PT Pfizer Indonesia
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