Dyslipidemia Management: New Guidelines & Total Vascular Benefit

PP-LIP-IDN-0090-JAN-2021
CV Heart Talk Series
Dyslipidemia Management:
New Guidelines & Total
Vascular Benefit
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Core Principles of
Dyslipidemia Management:
Guideline, Treatment Targets,
Lipid-lowering Therapy

FH, familial hypercholesterolemia; HC, hypercholesterolemia; LDL-C, low-density lipoprotein cholesterol; RRR, relative risk reduction.
Packard CJ. Trends Cardiovasc Med 2018;28:348-354.
Age and the impact of LDL-C on atherosclerosis
Greater RRR per
mmol/l reduction
Plaque resolution
Fatty streaks
LDL
chol
(mmol/l)
Lesser RRR
Plaque stabilisation
Complex plaque
Response to initiation of LDL lowering
Artery wall
LDLc rise with age (men)
Integrated LDL exposure
Polygenic HC
FH
Age (years)

ESC/EAS 2019 recommendations for risk assessment
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
• 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

2019 ESC/EAS Guidelines: CV risk categories
*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 m2.
§A calculated SCORE ≥10% for 10-year risk of fatal CVD; FH with ASCVD or with another major risk factor.
ǁDiabetes mellitus without target organ damage, with diabetes mellitus duration ≥10 years or another additional risk factor.
¶eGFR 30-59 mL/min/1.73 m2.
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.
• Documented ASCVD*
• Diabetes mellitus†
• Severe CKD‡
• Very high levels of
individual risk factors§
VERY HIGH-RISK
• TC >8 mmol/L (>310
mg/dL); LDL-C >4.9
mmol/L (>190
mg/dL); BP ≥180/110
mmHg
• Diabetes mellitusǁ
• Moderate CKD¶
• Young patients (type 1
diabetes mellitus <35 years;
type 2 diabetes mellitus <50
years) with disease duration
<10 years, without other risk
factors
• Calculated SCORE ≥1% and
<5% for 10-year risk of fatal
CVD
• Calculated SCORE <1%
for 10-year risk of fatal
CVD
HIGH-RISK MODERATE-RISK LOW-RISK

Grundy SM, et al. Circulation 2019; 139:e1082-e1143.
• 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
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
AHA Cholesterol Guidelines 2018
Executive summary: Risk enhancers

ESC/EAS 2019 LDL-C: Goals for patients of different risk
levels
Risk Group New (2019) LDL-C goals Previous (2016) LDL-C goals
Very high including T2DM
≥50% LDL reduction and
<1.4 mmol/L (<55 mg/dL)
ASCVD + another event within
2 years: consider LDL-C goal
<1.0 mmol/L (<40 mg/dL)
<1.8 mmol/L (<70 mg/dL) or ≥50% ↓ if baseline
1.8–3.5 mmol/L (70–135 mg/dL)
High including T2DM
≥50% LDL reduction and
<1.8 mmol/L (<70 mg/dL)
<2.6 mmol/L (<100 mg/dL) or ≥50% ↓ if baseline
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.

Risk stratification
Tailored regimen
Personalized approach
Patient preferences
Grundy SM, et al. Circulation 2019; 139:e1082-e1143.
LDL-C, Low density Lipoprotein-Cholesterol; ASCVD, Atherosclerotic Cardiovascular Disease, AHA: American Heart Association
AHA Cholesterol Guidelines 2018:
Intervention algorithms
Age 0–19 y
Lifestyle to prevent or reduce
ASCVD risk
Diagnosis of familial
hypercholesterolemia  statin
Age 20–39 y
Estimate lifetime risk to encourage lifestyle to
reduce ASCVD risk
Consider statin if family history premature
ASCVD and LDL-C ≥160 mg/dL (≥4.1 mmol/L)
Age 40–75 y
LDL-C ≥70-<190 mg/dL (≥1.8-4.9
mmol/L) without diabetes mellitus
10-year ASCVD risk percent begins risk
discussion
Age >75 y: Clinical assessment, risk discussion
Risk discussion:
Emphasize lifestyle to
reduce risk factors
(Class I)
<5%
“Low risk”
5%-<7.5%
“Borderline risk”
≥7.5%-<20%
“Intermediate risk”
Risk discussion:
If risk enhancers present
then risk discussion
regarding moderate-
intensity statin therapy
(Class IIb)
Risk discussion:
If risk estimate + risk
enhancers favor statin,
initiate moderate-intensity
statin to reduce LDL-C by
30%-49% (Class I)
≥20%
“High risk”
Risk discussion:
Initiate statin to reduce
LDL-C ≥50% (Class I)
Diabetes mellitus and age 40-75 y:
Risk assessment to consider high-intensity statin (Class llia)
Diabetes mellitus and age 40-75 y: Moderate-intensity statin (Class I)
LDL-C ≥190 mg/dL (≥4.9 mmol/L): No risk assessment; High-intensity statin (Class I)
Primary prevention:
Access ASCVD risk in
each age group
emphasize adherence
to healthy lifestyle

Prospective Studies Collaboration Lancet 2007;370;1829-1839.
CHD, coronary heart disease; CI, confidence interval
Age, cholesterol and CHD risk –
Predicted greater relative risk reduction with early intervention
A B
Hazard
ratio
(95%
Cl)
Usual total cholesterol (1 mmol/L)
Age at risk (years):
80–89
70–79
60–69
50–59
40–49
Age at risk
(years):
70–79
60–69
50–59
40–49
Sex Number of
deaths
Men
Woman
Total
2919
2707
5626
Test for heterogeneity: x2
1=12.0 (p=0.0005)
Men
Woman
Total
7372
3457
10829
1=4.1 (p=0.04)
Men
Woman
Total
8594
1825
10419
1=0.3 (p=0.6)
Men
Woman
Total
5001
560
5561
1=1.5 (p=0.2)
Men
Woman
Total
1191
118
1309
1=0.0 (p=0.8)
Test for trend by age: x2
1=415 (p<0.0001)
0.79 (0.74–0.84)
0.92 (0.86–0.97)
0.85 (0.82–0.89)
0.80 (0.77–0.83)
0.86 (0.82–0.90)
0.82 (0.80–0.85)
0.71 (0.69–0.74)
0.73 (0.68–0.78)
0.72 (0.69–0.74)
0.59 (0.57–0.61)
0.55 (0.49–0.61)
0.58 (0.56–0.61)
0.45 (0.41–0.48)
0.43 (0.34–0.55)
0.44 (0.42–0.48)
Hazard ratio (95% Cl) for 1 mmol/L
Lower usual total cholesterol
80–89

Inherited vs pharmacologically based LDL lowering
‘Earlier is better’
Ference BA, et al. J Am Coll Cardiol 2015;65:1552-1561.
2x2 factorial mendelian randomization study: log-linear association between genetically and
pharmacologically mediated lower low-density lipoprotein cholesterol and risk of coronary heart
disease
Proportional
risk
reduction
(SE)
log
scale
Lower LDL-C (mg/dl)
Genetic variants
LDL lowering from
birth
LDL lowering trials
Average age 62 yrs
Combined
NPC1L1 & HMGCR LDL-C score
HMGCR LDL-C score
NPC1L1 LDL-C
score
NPC1L1
rs217386
PCSK9
rs2479409
HMGCR
rs12916
ABCG5/8
rs4299376 PCSK9
rs11206510
LDLR
rs2228671 LDLR
rs6511720
NPC1L1 LDL-C score
HMGCR LDL-C score
A to Z GISSI-P
PCSK9 46L
rs11591147
SEARCH
IMPROVE-IT
ALLHAT-LLT

1. Rosensen RS. Exp Opin Emerg Drugs 2004;9:269-279. 2. LaRosa JC, et al. N Engl J Med 2005;352:1425-1435.
Association of LDL-C with CHD risk in statin trials
Event
rate
(%)
LDL-C achieved mg/dL (mmol/L)
Rx - Statin therapy
PRA – pravastatin
ATV - atorvastatin
PROVE - IT – ATV
TNT – ATV80
HPS – Rx
CARE – Rx
LIPID – Rx
4S – Rx
LIPID – Placebo
CARE – Placebo
HPS – Placebo
TNT – ATV10
PROVE - IT – PRA
JUPITER – RSV
AFCAPS – Rx
AFCAPS – Placebo
WOSCOPS – Placebo
WOSCOPS – Rx
ASCOT – Placebo
JUPITER – Placebo
ASCOT – Rx
4S – Placebo
Secondary Prevention
Primary Prevention

2019 ESC/EAS Guidelines: Treatment algorithm for
pharmacological LDL-C lowering
Total CV assessment
Baseline LDL-C levels
Risk modifiers
imaging (subclinical atherosclerosis)
In selected low- and moderate-risk patients
Indication for drug therapy
Define treatment goal Lifestyle advice/ interventions
High potency statin at highest
recommended / tolerable dose to reach
the goal
LDL-C goal reached?
Follow-up annually, or
more frequently if
indicated
Add ezetimibe
LDL-C goal reached? Follow-up annually, or more frequently if indicated
Add PCSK9
inhibitor
• Secondary prevention (very high-risk)
• Primary prevention: patient with FH and
another major risk factor (very-high risk)
Consider adding
PCSK9 inhibitor
• Primary prevention: patients at
very-high risk but without FH
Y N
Y
N
N
Y
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.

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.

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
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.
AHA Cholesterol Guidelines 2018
Executive summary – statin choice
High intensity Moderate intensity Low intensity
LDL-C lowering ≥50% 30%–49% <30%
Statins Atorvastatin (40 mg) 80 mg
Rosuvastatin 20 mg (40 mg)
Atorvastatin 10 mg (20 mg)
Rosuvastatin (5 mg) 10 mg
Simvastatin 20–40 mg
Simvastatin 10 mg
… Pravastatin 40 mg (80 mg)
Lovastatin 40 mg (80 mg)
Fluvastatin XL 80 mg
Fluvastatin 40 mg BID
Pitavastatin 1–4mg
Pravastatin 10–20 mg
Lovastatin 20 mg
Fluvastatin 20–40 mg
High-, Moderate-, and Low-intensity Statin Therapy*

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

Atorvastatin reduced first and total vascular events
390 fewer total vascular events
with atorvastatin (1,218 events for
placebo, 828 events for atorvastatin)
Reductions by atorvastatin were
evident in each territory
Number
of
vascular
events
First event Second event Third event Fourth and subsequent
events
Atorvastatin Placebo Atorvastatin Placebo Atorvastatin Placebo Atorvastatin Placebo
-164
events
-102
events
-55
events
-69
events
Cerebrovascular Coronary Peripheral

Atorvastatin reduced first and total vascular events
Atorvastatin reduced:
• First vascular events by
27% (p<0.001)
• Total vascular events by
32% (p<0.001)
• Total vascular events by
10% during the first year
(p=0.19) and by 40%
after the first year
(p<0.001)
Expected
vascular
events
per
100
participants
Years since randomization
Placebo
total vascular
Atorvastatin
total vascular
Placebo first
vascular
Atorvastatin
first vascular
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
Cumulative incidence functions for first and total vascular
events
No. at risk
Placebo
Atorvastatin
2,366
2,365
2,301
2,287
2,255
2,229
2,192
2,176
2,139
2,123
1,009
1,028
159
140

Atorvastatin reduced events in all vascular territories
Over 6 years, 20 vascular events/100 participants were avoided with atorvastatin treatment
Total events
[Events per 100 participants]*
Atorvastatin
(n=2,365)
Placebo
(n=2,366)
HR (95% CI) p-value
Total vascular
Total cerebrovascular
Total coronary
Total peripheral
828 [42.3]
571 [28.2]
203 [10.8]
54 [2.8]
1,218 [62.7]
748 [37.1]
373 [20.1]
97 [4.8]
0.68 (0.60–0.77)
0.76 (0.66–0.88)
0.54 (0.42–0.70)
0.56 (0.35–0.89)
<0.001
<0.001
<0.001
0.014
* 6 years after randomization
Atorvastatin
better
Placebo
better

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.

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)
TST (French cohort):
Evaluating benefit of targeting lower LDL-C levels
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
Primary endpoint: composite of
ischemic stroke; MI; new symptoms
requiring urgent coronary or carotid
revascularization; and vascular death
Event
rate,
%
Strategy
<70 mg/dL
100±10 mg/dL
1073
1075
915
889
807
800
691
702
590
586
487
475
392
353
253
238
106
104
Time, year

Targeting lower LDL-C significantly reduced the
primary endpoint
HR 0.74 (95% Cl 0.57–0.95);
p=0.019
Absolute risk reduction = 3.3%
NNT = 30
Primary endpoint: composite of ischemic stroke; MI; new symptoms requiring urgent
coronary or carotid revascularization; and vascular death
Patients
(%)
Primary endpoint
<70 mg/dL
100±10 mg/dL
9.6
12.9

Targeting lower LDL-C significantly reduced
vascular events
Patients
(%)
Cerebral infarction/urgent carotid or
cerebral artery revascularization
All strokes
(Cerebral infarction or
intracranial hemorrhage)
Primary endpoint or intracranial
hemorrhage
<70 mg/dL (N=1073)
100±10 mg/dL (N=1075)
p=0.046
HR (95% CI) 0.73 (0.54–0.99)
p=0.023
HR (95% CI) 0.72 (0.54–0.96)
p=0.021
HR (95% CI) 0.75 (0.58–0.96)
6.7
9.1
7.5
10.4 10.3
13.6
Selected secondary outcomes

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)

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
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.
Class Level
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.

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
Myalgia (CK Normal)
RCTs: 1-5%
Observational studies/
clinical setting: 5-10%
Age, female sex, low BMI, high-risk medications*, comorbidities#,
Asian ancestry, excess alcohol, high levels of physical activity, and
trauma
Myositis/myopathy (CK > ULN) with
symptoms or objective weakness
Rare -
Rhabdomyolysis Rare -
Statin-associated autoimmune myopathy Rare -
New-onset DM
Depends on population;
more frequent if DM risk
factors are present
DM risk factors:
BMI ≥30, FBG ≥100 mg/dL; metabolic syndrome, HbA1c ≥6%
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; HbA1c, 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
Newman C, et al. Am J Cardiol 2006;97:61-67.
%
Atv 10 mg (n=7,258)
All cause
Treatment-associated
Atv 80 mg (n=4,798) Pbo (n=2,180)
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
Incidence of myalgia with atorvastatin (Atv) 10 and 80
mg compared with placebo (Pbo)
2.9
1.4
2.7
1.5
1.2 0.7

Statin therapy in Asian diabetic patients:
Effects on renal function
GFR, glomerular filtration rate; LDL-C, low-density lipoprotein cholesterol.
Han E, et al. Endocrinol Metab. 2017;32:274-280.
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
Objective: To investigate and compare the statins affecting renal function in Asian patients with diabetes
eGFR,
ml/min/1.73m
2
LDL-C,
mg/dL
Atorvastatin Rosuvastatin Atorvastatin Rosuvastatin
p=0.001
p=0.012 p<0.001
p<0.001
Baseline 1 year Baseline 1 year
Change in kidney function after statin use Change in lipid level after statin use

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.
Reference: Latest BPOM Approved Lipitor Local Product Document 2021 Full product information can be requested to:
PT Pfizer Indonesia
World Trade Center 3, 28th Floor
Jl. Jend. Sudirman Kav. 29-31
Jakarta 12920

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