Clinical Practice of Case Sharing

of Current Lipid Management

Syarief Hidayat
 Kasus
Seorang laki-laki berumur 48 tahun datang ke poliklinik
pasca perawatan 1 bulan yang lalu dengan infark
miokard akut post primary PCI
• Tidak ada riwayat hipertensi
• Tidak ada riwayat diabetes
• Tidak merokok
• Tidak ada riwayat keluarga dengan PJK
• Riwayat TIA 1 tahun yang lalu
• Menggunakan atorvastatin 40 mg
• Obat lain yang digunakan: aspirin, clopidogrel,
bisoprolol, ramipril
Pemeriksaan fisik:
• Tekanan darah 110/80 mmHg
• Pemeriksaan fisik lain dalam batas normal

Profil lipid:
• Kolesterol total 136 mg/dl
• LDL-C 68 mg/dl
• HDL-C 40 mg/dl
• Trigliserida 210 mg/dl

Ureum, kreatinin, gula darah, SGOT, SGPT dalam

batas normal.
Toraks foto normal, EKG OMI anteroseptal.
 Kategori risiko kardiovaskular
untuk penderita adalah?

A. Very high risk

B. High risk

C. Moderate risk

D. Low risk
 Berapa target kolesterol LDL
yang ingin dicapai?

A. <100 mg/dl

B. <70 mg/dl

C. <55 mg/dl

D. <40 mg/dl
 Bagaimana strategi terapi
untuk mencapai target tersebut?

A. Atorvastatin 40 mg

B. Atorvastatin 80 mg

C. Atorvastatin 40 mg + ezetimibe

D. Rosuvastatin 40 mg
 Pertanyaan
• Merlipatgandakan dosis statin akan menghasilkan berapa % tambahan
penurunan LDL?

A. 6%
B. 12%
C. 18%
D. >25%
 Doubling a Statin Dose Yields
Only 6% Incremental Drop in
LDL-C
Statin Rule of 6
Reduction of LDL-C, %

6% drop
6% drop
6% drop

0 10 20 30 40 50 60 70 80

Statin, mg

Adapted from Knopp RH. N Engl J Med. 1999;341:498–511; Stein EA. Am J Cardiol.
2002;89(suppl):50C–57C.
 Risk Benefit Ratio of Statin Titration
Atorvastatin Lovastatin Simvastatin
10 mg 20 mg 40 mg 80 mg 20 mg 40 mg 80 mg 40 mg 80 mg
0
% Decrease in LDL-C

-10

-20

-30

-40

-50

-60
2.5
Elevated Transaminases

2.0
(% of Patients)

x
2.3
1.5

x
7
1.
1.0

0.5

0.0
10 mg 20 mg 40 mg 80 mg 20 mg 40 mg 80 mg 40 mg 80 mg

Data from prescribing information for atorvastatin, lovastatin, simvastatin.

This does not represent data from a comparative study.
Statin limitation: dose titration raises
counterregulatory effect and cholesterol absorption
Atorvastatin 20mg Atorvastatin 80mg
+71%
% Change
80
+48%
60
P<0.05
40
P<0.05
20
0
-20
-40
Cholesterol
-60 P<0.05
P<0.05 production
(lathosterol)
-80
-100 -69% Cholesterol
-76% Absorption
Lamon Fava et al J Lipid Res 2007; 48: 1746-53 (campesterol)
 Counter regulation of cholesterol
absorption and synthesis

~50% ~50%

According to Sheperd J et al.

SheperdJ. EurHeart J 2001; 3(suppl E):E2-E512 Assmann G, et al. Curr Med Res Opin. 2008;24(1):249–259.
Bays H et al. ClinTher2004; 26(11):1758-1773
SantosaS et al. Life Sci2007; 80:505-51414
Bays H. Expert Opin Investig Drugs 2002; 11:1587-1604
PACE: Efficacy of Ezetimibe Added to
Atorvastatin Versus Atorvastatin Uptitration
orHigh-risk
Switching to Rosuvastatin 1
patients with hypercholesterolemia not at LDL-C <100 mg/dL (~2.6 mmol/L) on
a

atorvastatin 10 mg
EZ 10 mg + Atorva 10
mg n=90
EZ 10 mg + Atorva 10 EZ 10 mg + Atorva 10 mg
mg n=30 n=28

Atorva 20 mg EZ 10 mg + Atorva 20 mg
n=243 n=124
Atorva 10 mg
N=2,646
Atorva 20 mg Atorva 40 mg
n=240 n=126

Rosuva 10 mg EZ 10 mg + Atorva 20 mg
n=468 n=234

Rosuva 10 mg Rosuva 20
n=476 mg n=206
Week: - - Day 6 1
6 5 1 2
Double-blind Double-blind
Screening Run-In Randomizatio Treatment Treatment
n Phase I Phase II
n=1,547

Adapted with permission from Bays HE et al.1

a
High risk of CHD was defined as: 1) subjects without CVD who had type 2 diabetes, or ≥2 risk factors and a 10-year risk for CHD >20% as determined by
the Framingham calculation, or 2) subjects with CVD, including established coronary or other atherosclerotic vascular disease.
PACE = A randomized, double-blind, active-controlled, multicenter study of patients with Primary hypercholesterolemia and high cardiovascular risk who are
not adequately controlled with Atorvastatin 10 mg: a Comparison of the efficacy and safety of switching to coadministration Ezetimibe and atorvastatin
versus doubling the dose of atorvastatin or switching to rosuvastatin
EZ = ezetimibe; Atorva = atorvastatin; Rosuva = rosuvastatin; CHD = coronary heart disease; CVD = cardiovascular disease.
1. Bays HE et al. Am J Cardiol. 2013;112:1885–1895.
 PACE Phase II: Greater Additional LDL-C Reduction
with Ezetimibe plus Atorvastatin 20 mg1

Ezetimibe as an adjunct to diet when diet and exercise alone are not enough
10
Treated Baseline at Week 6, %

LDL-C
IRLS Mean Change From

–10 –7%
–8

–20 –17% –17

–30 P<0.001 P<0.001

Adding ezetimibe 10 mg Doubling atorvastatin Switching from Doubling rosuvastatin
to atorvastatin 20 mg to 40 mg rosuvastatin 10 mg to to 20 mg
(n=124) (n=124) ezetimibe 10 mg + atorvastatin 20 mg (n=205)
Mean on-statin baseline Mean on-statin baseline (n=231) Mean on-statin baseline
LDL-C = 119 mg/dL LDL-C = 121 mg/dL Mean on-statin baseline LDL-C = 120 mg/dL
(~3.1 mmol/L) (~3.1 mmol/L) LDL-C = 119 mg/dL (~3.1 mmol/L)
(~3.1 mmol/L)

IRLS = iteratively reweighted least squares.

1. Bays HE et al. Am J Cardiol. 2013;112:1885–1895.
 PACE Phase II: Effect on Multiple Lipid
Parameters1
Ezetimibe as an adjunct to diet when diet and exercise alone are not enough

Adding ezetimibe 10 mg Doubling atorvastatin Switching from Doubling rosuvastatin

to atorvastatin 20 mga to 40 mgb rosuvastatin 10 mg to to 20 mgd
(n=124) (n=124) ezetimibe 10 mg + atorvastatin 20 mgc (n=205)
(n=231)

Total-C Apo B Non–HDL-C

0
Treated Baseline at Week 6, %

-5 –4
IRLS Mean Change From

–5 –4
–5 –6 –6
-10
–11 –10
–12 –12
-15
–15
–16
P<0.001 P<0.001
-20 P=NS P<0.001
P<0.001 P<0.001
-25

a
Mean treated baseline for group with ezetimibe added to atorvastatin 20 mg: Total-C 202 mg/dL (~5.2 mmol/L), apoB 102 mg/dL, non–HDL-C 151 mg/dL (~3.9 mmol/L)
b Mean treated baseline for group doubled to atorvastatin 40 mg: Total-C 203 mg/dL (~5.2 mmol/L), apoB 103 mg/dL, non–HDL-C 151 mg/dL (~3.9 mmol/L).
c
Mean treated baseline for group switched from rosuvastatin 10 mg to ezetimibe 10 mg + atorvastatin 20 mg: Total-C 204 mg/dL (~5.3 mmol/L), apoB 102 mg/dL,
non–HDL-C 151 mg/dL (~3.9 mmol/L).
d
Mean treated baseline for group doubled to rosuvastatin 20 mg: Total-C 203 mg/dL (~5.2 mmol/L), apoB 103 mg/dL, non–HDL-C 150 mg/dL (~3.9 mmol/L).
IRLS = iteratively reweighted least squares; Total-C = total cholesterol.
1. Bays HE et al. Am J Cardiol. 2013;112:1885–1895.
 TEMPO Study

Ezetimibe 10 mg + Atorvastatin 20 mg (n=98)

Atorvastatin 20 mg
(N=1,347 screened)

(N=196 randomized)

Atorvastatin 40 mg (n=98)

Visit 1 Week 0 Week 6

Run-in Double-Blind Period

Randomization
(LDL-C 100–160 mg/dL and
triglycerides ≤350 mg/dL)

72 Sites in the United States, Canada, Austria, and Costa Rica.

1. Conard SE et al. Am J Cardiol. 2008;102(11):1489–1494.
 Ezetimibe + Atorvastatin Provided Superior LDL-C–Lowering Efficacy vs Double the
Dose of Atorvastatin1

Ezetimibe 10 mg +
Atorvastatin 20 mg Atorvastatin 40 mg
(n=92) (n=92)
Baseline 120 mg/dL 118 mg/dL
0
Mean Change at

–10
Week 6, %

–11
–20

–30
–31a
–40
Reprinted from The American Journal of Cardiology, 102(11), Conard SE, Bays HE, Leiter LA, et al, Efficacy and safety of ezetimibe added on to
atorvastatin (20 mg) versus uptitration of atorvastatin (to 40 mg) in hypercholesterolemic patients at moderately high risk for coronary heart
disease, 1489–1494, © 2008, with permission from Elsevier.
a
P<0.001 vs atorvastatin 40 mg.
1. Conard SE et al. Am J Cardiol. 2008;102(11):1489–1494.
Pemeriksaan profil lipid bulan berikutnya
sebagai berikut:
• Kolesterol total 120 mg/dl
• LDL-C 40 mg/dl
• HDL-C 40 mg/dl
• Trigliserida 140 mg/dl
 Bagaimana terapi selanjutnya?

A. Lanjutkan Atorvastatin 40 mg + ezetimibe

B. Lanjutkan Atorvastatin 40 mg

C. Lanjutkan Atorvastatin 20 mg

D. Lanjutkan Simvastatin 20 mg
Conclusion
 Lipid Management

– Statins are first-line treatment for reduction of LDL-C1,2

– Despite guideline recommendations for the use of statins as first-
line treatment, dyslipidemia remains undertreated
– Modification of lifestyle, is necessary to halt the rise in CVD-
related mortality along with using Ezetimibe in addition to
Statins, for patients who could not achieve their target..

PLOS ONE | www.plosone.org 9 January 2014 | Volume 9 | Issue 1 | e84350*

Journal of Clinical Lipidology, Vol 8, No 3, June 2014**
THANK YOU