6. DR. MUHADI - Kasus Dislipidemia 8 Mei 2106

8/15/2019 6. DR. MUHADI - Kasus Dislipidemia 8 Mei 2106

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dr. Muhadi SpPD KKV, FINASIM

• Jakarta, August 22nd 1976

• Internist – Clinical Cardiologist FKUI-RSCM• ICCU RS Cipto Mangunkusumo, Jakarta

• American Heart Association Licenced BLS ACLS Instructors

• PB PAPDI (Perhimpunan Dokter Spesialis Penyakit Dalam

Indonesia)• PB IKKI (Ikatan Keseminatan Kardioserebrovaskular Indonesia)

• Anggota Komite Ahli Nasional Penanggulangan Penyakit Tidak

Menular, Kemkes RI 2015-2020


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Challenges in dyslipidemia

management and case study


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Step 2. Pemeriksaan Fisik dan Penunjang

• Pada pemeriksaan fisik pasien didapatkan BMI

23 kg/m2, TD 150/80 mmHg.

• Pasien kemudian diperiksakan lab dengan

hasil GDS 280 mg/dL, kolesterol total 260

mg/dL, Trigliserida 400 mg/dL, LDL 140

mg/dL, HDL 35 mg/dL


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Step 3. Menentukan Masalah

• Dislipidemia

• HT

• DM• Overweight


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Dislipidemia

• Dislipidemia adalah kelainan metabolismelipid yang ditandai dengan peningkatanmaupun penurunan satu atau lebih fraksi lipid

dalam darah.

• Beberapa kelainan fraksi lipid yang utama

adalah kenaikan kadar kolesterol total,kolesterol LDL, dan atau trigliserida, sertapenurunan kolesterol HDL.


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Dislipidemia

• No. ICPC (International Classification of Primary Care) II :

T93 Lipid disorder

• No. ICD (International Classification of Diseases) X :E78.5 Hiperlipidemia

• Tingkat Kemampuan: 4A Lulusan dokter mampumembuat diagnosis klinik dan melakukan

penatalaksanaan penyakit tersebut secara mandiri dan

tuntas.


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Level (mg/dl) Classification

240 High


>40 Minimum goal*

40-50 Desired goal*

>50 High


500 Very High

Total Cholesterol HDL-Cholesterol

Triglyceride

Source: Expert Panel on Detection, Evaluation, and Treatment of High BloodCholesterol in Adults. JAMA 2001;285:2486-2497

ATP III Classification of Lipoprotein Levels

*These goals apply to men. For women, the minimum goal is >50 mg/dL

HDL=High density lipoprotein


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HT

• Hipertensi adalah kondisi terjadinya

peningkatan TDS lebih dari ≥ 140 mmHg dan

atau TDD ≥ 90 mmHg.

• No ICPC II : K86 Hypertension uncomplicated

No ICD X : I10 Essential (primary) hypertension

• Tingkat Kemampuan: 4A


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DM

• DM adalah gangguan metabolik yang ditandai olehhiperglikemia akibat defek pada kerja insulin (resistensiinsulin) dan sekresi insulin atau kedua-duanya.

• ICPC II : T89 Diabetes insulin dependentT90 Diabetes non-insulin dependent

• ICD X : E10 Insulin-dependent diabetes mellitus

E11 Non-insulin-dependent diabetes mellitus

• Tingkat Kemampuan:a. Diabetes Melitus tipe 1 = 4Ab. Diabetes Melitus tipe 2 = 4A

c. Diabetes Melitus tipe lain = 3A


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Overweight

• No. ICPC II : T82 obesity, T83 overweight

• No. ICD X : E66.9 obesity unspecified

• Tingkat Kemampuan: 4A

Klasifikasi IMT untuk populasi Asia dewasa


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Step 3a. Stratifikasi Faktor Risiko


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SCORE Chart:

Assessment of Cardiovascular Risk Score http://www.heartscore.org/

European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J. 2012;33:1635 –1701

SCORE, Systematic Coronary Risk Evaluation Project; CVD, cardiovascular disease

10-year risk of fatal CVD is

based on risk factors: Age,

smoking, sex, systolic blood

pressure and total

cholesterol.


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10-year Atherosclerotic Cardiovascular Disease Using

Pooled Cohort Equations

Stone NJ, Robinson J, Lichtenstein AH et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report ofthe American College of Cardiology/American Heart Association Task Force on practice guidelines. 2013. Accessed January 28, 2014.


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Risk Stratification:

Framingham Risk Score On Line Calculator

Source: Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterolin Adults Risk Assessment Tool. http://hp2010.nhlbihin.net/atpiii/calculator.asp


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Step 3a. Stratifikasi Faktor Risiko

Qx Calculate

16.3 %

10-year risk of Atherosclerotic

Cardiovascular Disease (ASCVD)

> 30 % (High Risk)

Estimated 10 –year Global CVD Risk

11 % (Moderate Risk)


Wanita

58 thn

Ras Asia

Kol Total = 260 mg/dL

Kol HDL = 35 mg/dL

TDS = 150 mmHg

Pengobatan HT

DM *

Tidak merokok

Tidak ada riw peny

vaskular (PJK, PAD,

Stroke) *


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0 10 20

2 RFs

0-1 RFs

CAD or Risk Equivalent**

A risk assessment tool* is needed for individuals with >2 RFs

Source: Expert Panel on Detection, Evaluation, and Treatment ofHigh Blood Cholesterol in Adults. JAMA 2001;285:2486-2497

CAD=Coronary artery disease, CHD=Coronary heart

disease, DM=Diabetes mellitus, RF=Risk factor

**Includes DM, non-coronary atherosclerotic vascular disease, and

>20% 10-year CHD risk by the FRS

*Such as the Framingham Risk Score (FRS)

10-year CHD Risk

Risk Assessment for LDL C Lowering


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Slide 18

NIDDM = noninsulin-dependent diabetes mellitus

*Number of deaths/total patients

Adapted from Balkau B, et al. Lancet. 1997;350:1680.

M o r t a l i t y R a t e ,

D e a t h s p e r 1 0 0 0 P a t i e n t - y e a r s

Diabetes More Than Doubles Mortality Rate

Compared With Nondiabetic Controls

All-cause Mortality Ratio

Diabetes:No diabetes

No diabetesDiabetes (NIDDM)

Whitehall Study Paris ProspectiveStudy

HelsinkiPolicemen Study

05

10

15

20

25

30

35

(1998/10,025) (27/61) (1446/6629) (119/279) (175/631) (12/24)

2.48:1 2.16:1 2.06:1

N*=


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Slide 19

Cardiovascular Mortality Increases Sharply

With Serum Cholesterol Concentration in

Patients With Diabetes

Adapted from Stamler J, et al. Diabetes Care. 1993;16:434 –444.

D e a t

h s p e r 1 0 , 0

0 0 P e r s o n - y e a r s

100

50

0

Cholesterol Level

150


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Slide 20

Diabetes Established as

“CHD Risk Equivalent”

Fatal and nonfatal MI in subjects with and without type 2 diabetes mellitus

CHD = coronary heart disease; MI = myocardial infarction

*7-year incidence of fatal and nonfatal MI in 1373 nondiabetic and 1059 diabetic subjects

Adapted from Haffner SM, et al. N Engl J Med . 1998;339:229 –234.

0

5

10

15

20

25

30

35

40

45

50

No Prior MI Prior MI

I n c i d e n c e * ,

%

(n=890)(n=1304) (n=69) (n=169)

No Diabetes

Diabetes

3.5

20.2 18.8

45


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Pertanyaan


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Soal no.1

Pemeriksaan lanjutan yang paling tepat

dilakukan pada pasien untuk evaluasi

progresifitas penyakit ini adalah:

a. Darah perifer lengkap, asam urat

b. HbA1C, creatinin, EKG

c. Urinalisa lengkap, asam urat, HbA1c

d. USG Whole Abdomen, EKG


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Soal no.2

Pasien dengan masalah di atas memiliki resiko

tinggi untuk terjadi penyakit ?

a. Gagal ginjal kronik

b. Sirosis hepatis

c. Penyakit Jantung koroner

d. Kolesistisis


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3.7

2.9

2.2

1.7

1.3

1.0

40 70 100 130 160 190

R e l a t i v e

R i s k

f o r C o r o n a r y

H e a r t D i s e a s e ( L

o g

S c a l e )

LDL-Cholesterol (mg/dL)

Source: Grundy S et al. Circulation 2004;110:227-239

CHD=Coronary heart disease, LDL-C=Low-density lipoprotein cholesterol

Coronary Heart Disease Risk According to LDL C Level


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4.0

3.0

2.0

1.0

25 45 65

HDL-C (mg/dL)

C H

D r

i s k

r a t i o

2.0

1.0

0

4.0

Framingham Study

Source: Kannel WB. Am J Cardiol 1983;52:9B –12B

CHD=Coronary heart disease, HDL-

C=High-density lipoprotein cholesterol

CHD Risk According to HDL C Level


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Source: Sarwar N et al. Circulation 2007;115:450-458

CHD=Coronary heart disease

CHD Risk According to Triglyceride Levels

Meta-analysis of 29 prospective studies evaluating the risk of CHD relative

to triglyceride level (top third vs. bottom third)

An elevated triglyceride level is associated with increased CHD risk


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Soal no.3

Terapi farmakologi yang paling tepat diberikan

pada pasien adalah ?

a. Simvastatin 10 mg

b. Atorvastatin 20 mg

c. Gemfibrozil 300 mg

d. Ezetimibe


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Management of dyslipidaemia in women

ESC/EAS Guidelines for the management of Dyslipidemias 2011


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LDL Cholesterol

isThe Primary Target

in Dyslipidemia Treatment

NCEP ATP III 2003/ NCEP ATP III Update 2004

ADA/ACC Guideline Update for Secondary Prevention 2006

ESC/EAS Guidelines for the management of Dyslipidemias 20112013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce

Atherosclerotic Cardiovascular Risk in Adults


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Soluble fiber

Soy protein

Stanol esters

Dietary Adjuncts

Ezetimibe (Zetia)Cholesterol absorption inhibitor

Cholestyramine (Questran)

Colesevelam (Welchol)

Colestipol (Colestid)

Bile acid sequestrants

Atorvastatin (Lipitor)Fluvastatin (Lescol XL)

Lovastatin (Mevacor)

Pitavastatin (Livalo)

Pravastatin (Pravachol)

Rosuvastatin (Crestor)

Simvastatin (Zocor)

3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG-CoA) reductase inhibitors [Statins]

Drug(s)Class

Nicotinic acid Niacin

Therapies to Lower Levels of LDL C


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HDL-C=High-density lipoprotein cholesterol, LDL-C=Low-density lipoproteincholesterol, TC=Total cholesterol, TG=Triglyceride

Good- 9%+ 1%- 18%- 13%Ezetimibe

Good- 14-29%+ 4-12%- 25-50%- 19-37%Statins*

Good- 30%+ 11-13%- 4-21%- 19%Fibrates

Reasonable

to Poor- 30-70%+ 14-35%- 10-20%- 10-20%Nicotinic acid

PoorNeutral or+ 3%- 10-18%- 7-10%Bile acid

sequestrants

Patient

tolerabilityTGHDL-CLDL-CTCTherapy

Effect of Pharmacotherapy on Lipid Parameters

*Daily dose of 40mg of each drug, excluding rosuvastatin


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• In individuals without overt CV disease, the primary goal is an LDL-C


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Clinical ASCVD

• High-Intensity statin(age ≤75 years)

• Moderate-intensitystatin if >75 years ornot a candidate forhigh-intensity statin

LDL-C ≥190 mg/dL

• High-intensity statin

• Moderate-intensitystatin if not acandidate for high-intensity statin

Diabetes; age40-75 years*

• Moderate-intensitystatin

• High-intensity statin ifestimated 10 yearASCVD risk ≥7.5%

Estimated 10-yrASCVD risk ≥7.5%†;

age 40-75 years*

• Moderate- to high-intensity statin

ASCVD Statin Benefit GroupsHeart healthy lifestyle habits are the foundation of ASCVD prevention

2013 ACC/AHA Guideline Recommendations for

Statin Therapy

ASCVD prevention benefit of statin therapy may be less clear in other groups . Consider additional factors

influencing ASCVD risk , potential ASCVD risk benefits and adverse effects, drug-drug interactions, and patient

preferences for statin treatment.

* With LDL-C of 70-189 mg/dL† Estimated using the Pooled Cohort Risk Assessment Equations

Stone NJ, et al. J Am Coll Cardiol. 2013: doi:10.1016/j.jacc.2013.11.002. Available at:

http://content.onlinejacc.org/article.aspx?articleid=1770217. Accessed November 13, 2013.


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Target Terapi

Stratifikasi Risiko Risiko Target Kol LDL

ACC/AHA CV Risk (2013) 16.3 %

10-year risk of Atherosclerotic

Cardiovascular Disease (ASCVD)

Framingham Risk Score

(2008)

> 30 % (High Risk)


ATP III (2004)

LDL < 100 mg/dL

Optional goal < 70 mg/dL

Framingham Risk Score

(ATP III, 2004)

11 % (Moderate Risk)


ATP III (2004)

LDL < 130 mg/dL

Optional goal < 100mg/dL


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Risk Category LDL-C Goal Initiate TLC

Consider

Drug Therapy

High risk:

CHD or CHD risk equivalents

(10-year risk >20%)


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Risk Category LDL-C

0-1 < 160 mg/dl

2 (10-year risk


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High-Intensity Statin

Therapy

Moderate-Intensity Stain

Therapy

Low-Intensity Statin

Therapy

LDL –C ↓ ≥50% LDL –C ↓ 30% to


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Relative LDL-lowering efficacy of different

doses of statins

A t o r v a s t a t i n

F l u v a s t a t i n

P i t a v a s t a t i n

L o v a s t a t i n

P r a v a s t a t i n

R o s u v a s t a t i n

S i m v a s t a t i n

% d e c r e a s e i n

L D L - C

- 40 mg 1 mg 20 mg 20 mg - 10 mg 30%

10 mg 80 mg 2 mg 40 or 80

mg

40 mg - 20 mg 38%

20 mg - 4 mg 80 mg 80 mg 5 mg 40 mg 41%

40 mg - - - 10 mg 80 mg 47%

80 mg - - - 20 mg - 55%

- - - 40 mg - 63%

US FDA. Web site http://www.fda.gov/drugs/drugsafety/ucm256581.htm. Accessed on December 9, 2013.

Training Use Only

http://www.fda.gov/drugs/drugsafety/ucm256581.htmhttp://www.fda.gov/drugs/drugsafety/ucm256581.htm


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Benefit of HMG CoA ReductaseInhibitor (Statin)

• Lowering Total and LDL Cholesterol, Triglyceride

and raising HDL Cholesterol levels

• Antiatherothrombotic effects

• Improvement of endothelial function

• Anti-inflammatory effects

• Inhibition of arterial smooth muscle proliferation

• Prevention of oxidation of LDL Cholesterol

• Plaque stabilization effects on macrophages

Sattar N et al, Lancet 2010; Buse J et al. Clin Diabetes 2003


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Soal no.4

Pada pasien dengan pemakaian terapi

simvastatin jangka panjang, efek samping yang

paling sering terjadi dan perlu diperhatikan

adalah ?

a. Gejala gastrointestinal

b. Miositis

c. Gastritis

d. Alergi obat


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Source: Kashani A et al. Circulation 2006;114:2788-2797

• 1.4% incidence of elevatedhepatic transaminases (1.1%incidence in control arm)

• Dose-dependent phenomenon thatis usually reversible

• 15.4% incidence of myalgias*(18.7% incidence in control arm)

• 0.9% incidence of myositis (0.4%incidence in control arm)

• 0.2% incidence of rhabdomyolysis(0.1% incidence in control arm)

74,102 subjects in 35 randomized clinical trials with statins

*The rate of myalgias leading to discontinuation of

atorvastatin in the TNT trial was 4.8% and 4.7% in

the 80 mg and 10 mg arms, respectively

HMG CoA Reductase Inhibitor:

Adverse Effects

Hepatocyte

Skeletal myocyte


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Dosis simvastatin maksimal

• Pada tahun 2011, FDA Amerika Serikat

mengeluarkan rekomendasi baru tentang

keamanan simvastatin 80 mg.


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Dosis statin maksimal


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Dosis simvastatin maksimal

• Simvastatin yang digunakan dengan dosismaksimum (80 mg) berhubungan dengan miopatiatau jejas otot terutama jika digunakan selama 12

bulan berturutan.

• Simvastatin dosis 80 mg tidak dianjurkandiresepkan bagi pasien baru, melainkan bagimereka yang telah menggunakan dosis tersebutselama 12 bulan berturutan tanpa keluhan ataugejala miopati.

HMG CoA Reductase Inhibitor:


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Concomitant Use of Meds

Fibrate

Nicotinic acid (Rarely)

Cyclosporine

Antifungal azoles**

Macrolide antibiotics†

HIV protease inhibitors

Nefazadone

Verapamil, Amiodarone

Other Conditions

Advanced age (especially >80 years)

Women > Men especially at older age

Small body frame, frailty

Multisystem disease‡

Multiple medications

Perioperative period

Alcohol abuse

Grapefruit juice (>1 quart/day)

Risk factors for the development of myopathy*

Source: Pasternak RC et al. Circulation 2002;106:1024-1028

Adverse Effects

*General term to describe diseases of muscles

**Itraconazole, Ketoconazole†Erythromycin, Clarithromycin

‡Chronic renal insufficiency, especially from

diabetes mellitus


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Soal no.5

Terapi non farmakologis utama yang perlu

disarankan pada pasien adalah, kecuali ?

a. Turunkan berat badan

b. Olah raga rutin

c. Stop konsumsi jamu

d. Menjaga pola makan


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Intervensi gaya hidup yang dapat dilakukan untuk

mengurangi kolesterol LDL, kolesterol HDL dan TG


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Follow up

• Rekomendasi profil lipid yang diperiksa secara rutin adalahkolesterol total, kolesterol LDL, kolesterol HDL, dan TG.

• Kolesterol non-HDL dapat dihitung dengan mengurangkan

kolesterol HDL terhadap kolesterol total:

Kolesterol non-HDL = Kolesterol Total – Kolesterol HDL

• Dengan formula Friedewald dapat diperhitungkan bahwa:

Kolesterol LDL (mg/dL) = kolesterol total ̶ kolesterol HDL ̶

TG/5

(kecuali bila TG > 400 mg/dL atau dalam keadaan tidak puasa)


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Recommendations for monitoring lipids in

patiens on lipid-lowering therapy


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Follow Up

• Jika memungkinkan, sampel darah diambil setelah puasa 12

jam (diperlukan untuk pemeriksaan TG yang juga dipakai

untuk penghitungan konsentrasi kolesterol LDL memakai

formula Friedewald).

• Kolesterol total dan HDL dapat diperiksa dalam keadaan tidak

puasa.

• Konversi dari mg/dL menjadi mmol/L :

Untuk kolesterol total, LDL dan HDL: dikalikan 0,0259

Untuk TG: dikalikan 0,0113


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Recommendations for monitoring enzymes in

patiens on lipid-lowering therapy


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NEXT ???


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Treatment of low HDL

cholesterol (


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Non-HDL Cholesterol

• LDL-C is the primary goal of therapy for

persons with dyslipidemia

• Non HDL Chol is a secondary goal of therapy in

persons with TG >= 200 mg/dl

• Non HDL-C = Total Cholesterol – HDL C

= VLDL Chol + LDL C


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ATP III: Management of


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56

©2004 PPS®

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.

*Primary aim of therapy is to get to LDL-C goal.†Primary aim of therapy is to reduce risk for pancreatitis through TG lowering first,then focus on LDL-C.‡To achieve non–HDL-C goal (set at 30 mg/dL higher than LDL-C goal), intensifytherapy with LDL-C–lowering drug, or add nicotinic acid or fibrate.

Classification TG Level (mg/dL) Treatment Strategy

Borderline high* 150 –199

weight, physical activity

High* 200 –499

weight, physical activity,consider drug treatment to reach

non –HDL-C goal‡

Very high†

500 Very low-fat diet, weight,physical activity, nicotinic acid or

fibrate

ATP III: Management of Elevated TG


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Most physicians believe they adhere to guidelines, but

most patients remain undertreated

0

10

20

30

40

50

60

70

80

90

100

US UK Australia France Germany

P h y s i c i a n s w h o r e p o r t b e i n

g c o n s i s t e n t w i t h

o r m o r e a g g r e s s i v e t h a n

g u i d e l i n e s ( % )

% of treated patientsreaching goal

Basis for

% reaching goal : L-TAP EUROASPIRE II VIC II EUROASPIRE II EUROASPIRE II

Pearson T et al. Arch Intern Med. 2000;160:459-467. EUROASPIRE II Study group. Eur Heart J. 2001;22:554-72.

Vale M et al. Med J Aust. 2002;176:211-215. Physician self-reported behavior based on Pfizer Market Research.

TERIMA KASIH


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ObesityDiabetesHypertension Dyslipidemia

TERIMA KASIH

6. DR. MUHADI - Kasus Dislipidemia 8 Mei 2106

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