Lipid management update in

high risk patients: How to deal

with International Guidelines?
Tsunami of Cardiovascular Disease Targets Indonesia
 Serangan Jantung & Stroke merupakan penyebab
kematian utama di Indonesia 1,2

Tingginya angka
kematian di
Indonesia akibat
Penyakit
Jantung
Stroke Koroner Tingginya kadar
merupakan mencapai 26%.1 kolesterol LDL
penyebab dan tekanan darah
kematian merupakan 2
faktor risiko utama
utama di
serangan Jantung
Indonesia. 2 & Stroke.3

1. Hasil Survei Kesehatan Rumah Tangga Nasional (SKRTN) DEPKES tahun 2001
2. Badan Penelitian dan Pengembangan Kesehatan Kementrian Kesehatan RI. Riset Kesehatan Dasar. 2013.
http://www.depkes.go.id/resources/download/general/Hasil%20Riskesdas%202013.pdf
3. The atlas of heart disease and stroke. World Health Organization website. http://www.who.int/cardiovascular_diseases/resources/atlas/en/.
Need for optimization of treatment dyslipidemia
to maximize benefit and improve outcome
 Kelas Rekomendasi
(Class of recommendations)
KELAS SARAN
DEFINISI
REKOMENDASI PENGGUNAAN KATA
Kelas I Terbukti dan/atau persetujuan umum bahwa Direkomendasikan /
pemberian terapi atau prosedur bermanfaat, Diindikasikan
berguna, efektif
Kelas II Ada pertentangan bukti dan/atau perbedaan
opini mengenai kegunaan/efikasi terapi atau
prosedur
Kelas IIa Tingkat bukti/opini lebih besar ke Harus
kegunaan/efikasi dipertimbangkan
Kelas IIb Kegunaan/efikasi kurang didukung bukti/opini Dapat
dipertimbangkan
Kelas III Terbukti/persetujuan umum bahwa pemberian Tidak
terapi atau prosedur tidak memiliki direkomendasikan
kegunaan/manfaat; dan pada beberapa kasus
mungin berbahaya
 Tingkat Bukti
(Level of Evidence)

Data didapat dari banyak penelitian klinis acak (RCT –

Level of Evidence A
Randomized Clinical Trials) atau meta-analisis

Data didapat dari satu penelitian klinis acak (RCT –

Level of Evidence B Randomized Clinical Trials) atau penelitian klinis tanpa
acak (non-randomized studies) yang besar

Konsensus atau opini ahli dan/atau studi kecil, studi

Level of Evidence C
retrospektif, dan studi registri
 New 2013 ACC/AHA Guidelines identify 4 Statin benefit
groups: Shift from a target-based approach to a drug
and dose-based approach

Group 1 Group 2

Clinical ASCVD LDL-C ≥190 mg/dL

CHD, stroke, and
peripheral arterial
disease, all of presumed
atherosclerotic origin

Group 3 Group 4

Diabetes mellitus ASCVD risk ≥7.5%

+ age of 40–75 years No diabetes

+ LDL-C 70–189 mg/dL + age of 40–75 years
(1.8–4.9 mmol/L) + LDL-C 70–189 mg/dL
(1.8–4.9 mmol/L)

ASCVD, atherosclerotic cardiovascular disease

CHD, coronary heart disease 17
LDL-C, low-density lipoprotein-cholesterol Stone NJ, et al. J Am Coll Cardiol 2013 Nov 7. Epub ahead of print
 Intensity of Treatment
• (Group1) Known ASCVD: high-intensity statin*
• (Group2) LDL-C >190 mg/dl: high-intensity statin*
* Unless >75 years old or statin-intolerant, then use moderate-intensity statin

• (Group3) Diabetes, age 40-75, LDL-C 70-189 mg/dl:

moderate-intensity statin unless score ≥7.5%, then
high-intensity statin
• (Group4) Patients aged 40-75, LDL-C 70-189 mg/dl
with a global 10-year risk score of ≥7.5%: moderate
to high-intensity statin

2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce

Atherosclerotic Cardiovascular Risk in Adults
 Intensity of Statin Therapy
High Moderate Low
 LDL-C ≥50%  LDL-C 30 to <50%  LDL-C <30%
Atorva 40-80 mg Atorva 10-20 mg Simva 10 mg
Rosuva 20-40 mg Rosuva 5-10 mg Prava 10-20 mg
Simva 20-40 mg Lova 20 mg
Pravas 40 mg Fluva 20-40 mg
Lova 40 mg Pitava 1 mg
Fluva XL 80 mg
Fluva 40 mg bid
Pitava 2-4 mg

Statins in bold were evaluated in randomized controlled trials;

those in italics were not

2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce

Atherosclerotic Cardiovascular Risk in Adults, p 34
Pooled Cohort Equations for ASCVD Risk
Prediction

ACC/AHA Guideline on the Assessment of cardiovascular Risk : A report of the American College of Cardiology/American
Heart Association Taskforce on practice guideline, 2013
ACC/AHA Guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of
the American College of Cardiology/American Heart Association Taskforce on practice guideline, 2013
20
ACC/AHA Guidelines Recommendations for Nonstatin
Drugs (Fibrates & Ezetimibe)

 The panel could find no data supporting the routine use of nonstatin
drugs added to statin therapy to further reduce ASCVD events
 In addition, identification of any RCT’s that assessed ASCVD outcomes in
statin-intolerant patients was not found

Fenofibrate dapat dipertimbangkan untuk digunakan bersama moderate/low

intensity statin hanya bila manfaatnya untuk menurunkan risiko ASCVD
ATAU menurunkan TG ketika kadarnya > 500 mg/dL, melebihi
risiko efek samping yang potensial
1. Stone NJ et al. J Am Coll Cardiol 2014;63:2889–2934
 Points of Agreement: ESC 2016 &
ACC/AHA 2013
When the risk is high, treatment should be
intensive

The ESC/EAS and IAS recommend LDL-lowering

therapy to achieve LDL-C goals

The ACC/AHA recommend the use of high intensity

statin therapy to reduce LDL-C by >50%.
 Points of Agreement: ESC 2016 &
ACC/AHA 2013

When the risk is moderately high, treatment

should be moderately intensive

The ESC/EAS and IAS recommend LDL-lowering

therapy to achieve LDL-C goals

The ACC/AHA recommend the use of moderate

intensity statin therapy to reduce LDL-C by >30%.
 Minor Points of Disagreement: ESC
2016, ACC/AHA 2013, NICE 2014
 Each uses different algorithms to calculate risk

 ACC/AHA version does not identify LDL-C goals

 ACC/AHA guidelines tend to deemphasize non-statin

drugs

 2014 NICE (UK) guidelines recommend atorvastatin

as the statin of choice for both primary prevention (20
mg) and secondary prevention (80 mg)
ESC-EAS Lipid Guidelines. Eur Heart J. 2016; On line 27 August
National Institute for Health and Care Excellence (UK); 2014
2013 ACC/AHA Lipid Guidelines. Circulation2014 Jun 24;129(25 Suppl 2):S1-45.
IAS Lipid Management Recommendations. J Clin Lipidol. 2014; 8:29
 So

• There are many points of agreement in

recent guidelines for the management of
plasma lipids
• All emphasize the importance of lifestyle
measures to reduce risk
• All agree that LDL-C is a primary target for
therapy to reduce ASCVD risk
• All agree that treatment decisions should be
based on overall CV risk rather than plasma
lipid levels alone
High Incidence of Clinical Events 30 Days Post-ACS
Indicates Need for More Aggressive Treatment

Incidence of death, MI, or recurrent angina at 30 days

35
Patients experiencing recurrent event (%)

30

25

20

15

10

0
Argentina France UK Canada US Netherlands

Fox KAA et al. Eur Heart J. 2000;21:1433-1439.

26
 Many Patients With ACS Are Not on Statin Therapy
When Discharged

Percentage of ACS patients discharged without statin therapy

90 82
80 72
68
Patients with ACS (%)

70
60
50
40
30
16
20
10
0
NRMI PURSUIT/GUSTO Swedish Register MINAP
of CIC
2001 2001 2001 2004

MINAP=National Audit of Myocardial Infarction Project.

Fonarow GC et al. Circulation. 2001;103:38-44; Aronow HD et al. Lancet. 2001;357:1063-1068; Stenestrand U et al. JAMA. 2001;285:430-436;
Birkhead JS et al. Heart. 2004;90:1004-1009.
27
O’Gara et al. 2013 ACCF/AHA STEMI Guideline. JACC Vol.61.No.4.2013:e78-140
 Lipid Management Recommendation

O’Gara et al. 2013 ACCF/AHA STEMI Guideline. JACC Vol.61.No.4.2013:e78-140

O’Gara et al. 2013 ACCF/AHA STEMI Guideline. JACC Vol.61.No.4.2013:e78-140
 Lipid Management Recommendation
• Treatment with statins in
patients with stabilized
after ACS (include STEMI)
lower the risk of CHD,
death, recurrent MI, stroke,
and coronary
revascularization
• Only High-Dose
Atorvastatin has been
shown to reduce death and
ischemic events amongst
patients with ACS
• Statin therapy after ACS is
O’Gara et al. 2013 ACCF/AHA STEMI beneficial even in patients
Guideline. JACC Vol.61.No.4.2013:e78-140
with baseline LDL<70
mg/dL
PROVE-IT TIMI 22: Atorvastatin for reduction of CV risk
in patients with ACS

Study design highlights

Patient population: Double-blind period

 Enrolled at 349 sites in

eight countries
 Men and women,
aged ≥18 years
 Hospitalized for an ACS in the
preceding 10 days
 Total-C ≤240 mg/dL or total-C
≤200 mg/dL if receiving lipid-
lowering therapy
Atorvastatin 80 mg/d
4162
patients
Pravastatin 40 mg/d
Mean 2-year follow-up
(925 primary events)

Primary endpoint:
 Time to the first occurrence of a
major CV event

Cannon CP, et al. N Engl J Med 2004;350:1495–1504

 PROVE-IT: Atorvastatin reduces CV risk in patients
with ACS

 PROVE-IT: atorvastatin 80 mg reduced the risk of death or a major CV event

by 16% (p=0.005) compared with pravastatin 40 mg in patients with ACS

Incidence of death or major CV events*

30
16%
Death or major CV event (%)

25 RRR
95% CI,
20 5 to 26%
(p=0.005)
ARR 3.9%
15 NNT 26
over 2 years
10
Pravastatin 40 mg (n=2063). Median LDL-C 95 mg/dL
5 Atorvastatin 80 mg (n=2099). Median LDL-C 62 mg/dL

0
0 0.5 1.0 1.5 2.0 2.5
Time (years) Cannon CP, et al. N Engl J Med 2004;350:1495–1504
*Major CV events: MI, unstable From New England Journal of Medicine, Cannon CP, et al. Intensive versus
angina requiring hospitalization, Moderate Lipid Lowering with Statins after Acute Coronary Syndromes, 350, 1495–1504.
revascularization, and stroke Copyright ©(2004) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society
PROVE-IT: Benefit of atorvastatin over pravastatin was
evident at 30 days

 PROVE-IT: atorvastatin 80 mg reduced the composite triple endpoint

(death, MI, or rehospitalization for ACS) within 30 days of randomization
 This benefit remained stable from 30 days onward

5
ARR 1.2% NNT=83 over 30 days
28%
Death, MI, or rehospitalization

4 RRR
for ACS (%)

HR 0.72
3 95% CI,
0.52 to 0.99
(p=0.046)
2

1 Pravastatin 40 mg (n=2063). Mean LDL-C at 30 days=88 mg/dL

Atorvastatin 80 mg (n=2099). Mean LDL-C at 30 days=60 mg/dL

0
0 5 10 15 20 25 30
Time (days following randomization)
Ray K, et al. JACC 2005;46:1405–1410
Reprinted from Journal of the American College of Cardiology, Volume 46, Ray K, et al. Early and Late Benefits of High-Dose Atorvastatin
in Patients With Acute Coronary Syndromes, 1405–1410. Copyright (2005), with permission from Elsevier
 PROVE-IT: Atorvastatin reduces acute cardiac events
in patients with ACS and diabetes

 PROVE-IT (sub-analysis): atorvastatin 80 mg reduced the risk of acute

cardiac events by 25% (p=0.03) compared with pravastatin 40 mg in a
post hoc analysis of patients with recent ACS and type 2 diabetes
Incidence of acute cardiac events*

25%
RRR
(p=0.03)
ARR 5.5%
NNT 18
over 2 years
Median Median
LDL-C at LDL-C at
30 days: 30 days:
57 mg/dL 81 mg/dL

(n=499) (n=479)
Ahmed S, et al. Acute coronary syndromes and diabetes: is intensive lipid lowering beneficial?
Results of the PROVE IT-TIMI 22 trial. European Heart Journal, 2006,
*Death, MI, and unstable angina requiring hospitalization 27(19), 2323–2329, by permission of Oxford University Press
 ARMYDA-ACS trial: Study design
580 pts excluded for:
- 451 statin therapy
- 41 emergency angiography
- 43 LVEF <30%
- 30 contraindications to statins 20 pts excluded for indication to:
- 15 severe renal failure - medical therapy (N=8)
- bypass surgery (N=12)

30 days
Atorvastatin 80 mg
12 hrs pre-angio;
further 40 mg
Randomization (N=191)

PCI
2 hrs before
atorvastatin
N=96 N=86
771 pts with atorvast Primary
NSTE-ACS Coronary combined
sent to angiography end point:
early coronary PCI
Placebo placebo 30-day
angiography 12 hrs pre-angio; N=85 death, MI,
(<48 hours) further TVR
Jan ’05 - Dec ‘06 dose 2 hrs
before
N=95
1st blood sample 2nd and 3rd
blood samples
(pre-PCI)
(8 and 24 hrs
Primary end point:
Incidence of major adverse cardiac events post-PCI)
(MACE: death, MI, TVR) from the
procedure up to 30 days
CK-MB, troponin-I, myoglobin, CRP
 ARMYDA-ACS trial
Composite primary end-point (30-day death, MI, TVR)

88% Risk Reduction of MACE

% 20 17

15 P=0.01

Atorvastatin
10
Placebo
5
5

MACE = Major Acute Cardiovascular Events

37
 ARMYDA-ACS
Individual and Combined Outcome Measures
of the Primary End Point at 30 days
21
14/85
% 18 13/85 (17%)
(15%)
15 P=0.01
P=0.04
12
9
4/86 4/86
6 (5%) (5%)
1/85
3 (2%)

0
Death MI TVR MACE
Composite
Primary End Point
Atorvastatin Placebo

38
 2014

Kernan W, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline
for healthcare professionals from the American Heart Association/ American Stroke Association. Stroke. 2014;45(7):2160-
2236
SPARCL: Study Design

Patient Population Double-blind period

 ~200 sites worldwide Atorvastatin 80 mg/d

 Documented stroke
or TIA within previous 4732
6 months Patients
 No history of CHD
Placebo
 LDL-C levels ≥100
mg/dL and
≤190 mg/dL 540 primary end points

Primary End Point

Time to the first occurrence of a fatal or nonfatal stroke
TIA = transient ischemic attack; CHD = coronary heart disease; LDL-C = low-density
lipoprotein cholesterol.
The SPARCL Investigators. Cerebrovasc Dis. 2003;16:389–395.
Placebo

Atorvastatin
 Secondary Endpoint:
Time to Major Coronary Event
8%
Major Coronary Event (%)

6% 35%
RR

4%
Placebo
Atorvastatin

2%

Adjusted HR (95% CI)* = 0.65 (0.49, 0.87), p = 0.003

0%
0 1 2 3 4 5 6
Years Since Randomization
* Treatment effect from Cox proportional hazards models with pre-specified adjustment
for geographical region, entry event, time since entry event, gender, and baseline age.
Amarenco P, Bogousslavsky J, Callahan A III, et al. N Engl J Med. 2006;355:549-59
Statin Therapy Is Not Associated With Increased
Risk for Hemorrhagic Stroke
A recent meta-analysis demonstrated that statin therapy does not increase
risk of hemorrhagic stroke vs control

Trials Odds Ratios (95% Cl)

HPS
GREACE*
MIRACL
KLIS*
LIPID
CARE
4S
AFCAPS
OVERALL (95% Cl) HR 0.90 (0.65-1.22)
Heterogeneity P=.15

0.05 0.2 0.5 1.0 3.0 10.0

*Statin vs usual care. Favors statin Favors control

Adapted with permission from Amarenco P et al. Stroke. 2004;35:2902-2909.

 High Intensity Statins & Renal
Safety ?

44
 45
PLANET I and II investigated the effects of atorvastatin and
rosuvastatin on renal function
in patients with CKD with and without diabetes

PLANET I and II were multicenter, randomized, double-blind studies

Patient population 52 weeks follow-up

PLANET I
 Type I or II diabetes
Rosuvastatin 40 mg/day
PLANET II
 No diabetes PLANET I: n=325*
Both studies PLANET II: n=220*
Rosuvastatin 10 mg/day
 Moderate proteinurea1
 Hypercholesterolemia2 Atorvastatin 80 mg/day
 ACEis or ARBs for ≥3
months prior to screening

 Primary endpoint: Within-group change in urinary protein/creatinine ratio (UPCR) from

baseline to Week 52 or last on-treatment observation carried forward (Week 52 LOCF)

*Intention-to-treat (ITT) populations

1.Urinary protein/creatinine ratio 500–5,000 mg/g;
2.Fasting LDL-C ≥90 mg/dL (2.33 mmol/L);
ACEi, angiotensin converting enzyme inhibitor; De Zeeuw D, et al. Lancet 2015. http://dx.doi.org/10.1016/S2213-
ARB, angiotensin receptor blocker 8587(14)70246-3
 46
PLANET I: Effect of atorvastatin or rosuvastatin on
urinary protein/creatinine ratio
Rosuvastatin 10 mg
1.4 Rosuvastatin 40 mg
Atorvastatin 80 mg
UPCR (Baseline: on-treatment)

1.2

1.0 p=0.83
p=0.53
p=0.033
0.8

0.6
0
0 14 26 39 52 LOCF
Number of patients Time (weeks)
Rosuvastatin 10 mg 107 103 97 96 95 107
Rosuvastatin 40 mg 116 112 107 106 106 116
Atorvastatin 80 mg 102 96 91 88 82 102

Data are mean baseline: on-treatment ratios

Error bars are 95% CIs. LOCF marks 52-week data accounting for all
patients in ITT population Reprinted from The Lancet, 3, de Zeeuw D, et al, Renal effects of
LOCF, last observation carried forward; UPCR, urinary atorvastatin and rosuvastatin in patients with diabetes who
protein/creatinine ratio have progressive renal disease (PLANET I): a randomised clinical
p values are vs baseline trial, 181–190. Copyright (2015), with permission from Elsevier
 47
PLANET I: Effect of atorvastatin or rosuvastatin on
estimated glomerular filtration rate
Rosuvastatin 10 mg
2 Rosuvastatin 40 mg
Atorvastatin 80 mg
0
(mL/min per 1.73 m2)

p=0.21
Change in eGFR

–2

–4

–6
p=0.0098
p=0.0002
–8

–10
0 4 8 14 26 39 52 LOCF
Number of patients Time (weeks)
Rosuvastatin 10 mg 107 106 104 103 99 95 95 107
Rosuvastatin 40 mg 116 115 112 111 109 104 109 116
Atorvastatin 80 mg 102 99 98 97 92 86 86 102

Data are mean changes from baseline

Error bars are 95% CIs. LOCF marks 52-week data accounting for all
patients in ITT population Reprinted from The Lancet, 3, de Zeeuw D, et al, Renal effects of
eGFR, estimated glomerular filtration rate; LOCF, last observation atorvastatin and rosuvastatin in patients with diabetes who
carried forward have progressive renal disease (PLANET I): a randomised clinical
p values are vs baseline trial, 181–190. Copyright (2015), with permission from Elsevier
 48

PLANET I: Reported adverse events

Rosuvastatin Rosuvastatin Atorvastatin

n (%) 10 mg (n=116) 40 mg (n=123) 80 mg (n=110)
Any adverse event 69 (59.5) 79 (64.2) 63 (57.3)

Any serious adverse event* 18 (15.5) 20 (16.3) 21 (19.1)

Any renal adverse event 9 (7.8) 12 (9.8) 5 (4.5)

Acute renal failure 0 5 (4.1) 1 (0.9)

Serum creatinine doubling 0 6 (4.9) 0

Serum creatinine doubling
0 9 (7.3) 1 (0.9)
or acute renal failure
Death 4 (3.4) 1 (0.8) 0

Statistical analysis of adverse events was not presented

One serious AE (2 episodes of cardiac failure in rosuvastatin 10 mg group) was considered related to study drug

No episodes of acute renal failure were considered related to study drug

Reprinted from The Lancet, 3, de Zeeuw D, et al, Renal effects of atorvastatin and
rosuvastatin in patients with diabetes who have progressive renal disease (PLANET I): a
randomised clinical trial, 181–190. Copyright (2015), with permission from Elsevier
Clinical trials of atorvastatin have reported reductions
in CV events across multiple patient populations

Regimen
Study Population follow-up Lipid effects CV endpoints
Hypertension, Atorvastatin 10 mg Final LDL-C
Nonfatal MI + fatal CHD
ASCOT-LLA1 high total-C Placebo Atorvastatin 90 mg/dL
↓36% (p=0.0005)
(n=10 305) (Median 3.3 years) Placebo 126 mg/dL
Type 2 Atorvastatin, 10 mg Final LDL-C
CARDS2 Major CV events ↓37%
diabetes, no Placebo Atorvastatin: 83 mg/dL
(p=0.001)
CHD (n=2838) (Median ≈3.9 yr) Placebo: 111 mg/dL
Atorvastatin, up to
Final LDL-C
Stable CHD 80 mg CV events ↓17%
ALLIANCE3 Atorvastatin: 95 mg/dL
(n=2442) Usual care (p=0.026)
Usual care: 111 mg/dL
(Mean 4.3 yr)

Atorvastatin, 80 mg Final LDL-C

Stable CHD Major CVD events ↓22%
TNT4 Atorvastatin, 10 mg 80 mg: 77 mg/dL
(n=10 001) (p<0.001)
(Median 4.9 yr) 10 mg: 101 mg/dL

Prior Atorvastatin 80 mg LDL-C during study

Fatal or nonfatal stroke
SPARCL5 stroke/TIA Placebo Atorvastatin 73 mg/dL
↓16% (p=0.03)
(n=4731) (Median 4.9 years) Placebo 128 mg/dL

1. Sever PS, et al. Lancet 2003;361:1149–1158; 2. Colhoun HM, et al. Lancet. 2004;364:685–696;
3. Koren MD, et al. J Am Coll Cardiol 2004;44:1772–1779; 4. LaRosa JC, et al. N Engl J Med 2005;352:1425–1435;
5. Amarenco P, et al. N Engl J Med. 2006;355:549–559
 Atorvastatin has established evidence of CV event
reduction across a wide range of patients

Atorvastatin Rosuvastatin

Rosuvastatin has not

been assessed in an
outcomes trial of
patients with diabetes

1. Sever PS et al. Lancet 2003;361:1149–58; 2. Colhoun HM et al. Lancet 2004;364:685–96;

3. Sever PS et al. Diabetes Care 2005;28:1151–57; 4. Koren MJ, Hunninghake DB, on behalf of the ALLIANCE Investigators, J Am
ACS, acute coronary syndrome Coll Cardiol 2004;44:1772–79; 5. Athyros VG et al. Angiology 2003;54(6):679–90;
CKD, chronic kidney disease 6. Shepherd J et al. J Am Coll Cardiol 2008;51:1448–54; 7. Schwartz GG et al. JAMA 2001;285:1711–18;
CRP, C-reactive protein 8. SPARCL Investigators. N Engl J Med 2006;355:549–59; 9. Ridker PM et al. N Engl J Med 2008;359:2195–207;
50
TIA, transient ischemic attack 10. Koenig W, Ridker PM. Eur Heart J 2011;32(1):75–83; 11. Ridker PM et al. J Am Coll Cardiol 2010;55(12):1266–73.
Atorvastatin versus rosuvastatin

 Atorvastatin has been evaluated in a larger number of CV outcome trials (11)

than rosuvastatin (4)
 Atorvastatin has an established safety profile which includes patients with
CKD

Patient characteristics Atorvastatin Crystalline Rosuvastatin

10-80 mg 1–3 5-40 mg 4
Initiation at any dose in YES NO
(recommended start dose
Asian patients 5 mg)

Elderly YES NO
(recommended start dose
(>70 years of age) 5 mg)

Severe renal impairment YES NO

(recommended start dose
(CrCL < 30 mL/min) 5 mg and NOT to exceed
10 mg)

1. Harper CR, Jacobson TA. J Am Coll Cardiol 2008;51:2375–2384;

2. LIPITOR Product Document; 3. Newman CB et al. Am J Cardiol 2006;97:61–67;
4. Crestor (Rosuvastatin calcium) Prescribing Information. AstraZeneca, December 2012 51