atorwin rtd 2014 dr sukartono

Dyslipidemia Management with Better CVD Risk Prevention

Dyslipidemia Management with Better CVD Risk Prevention

Dr Sukartono Toposubroto SpPDRSI Pekajangan Pekalongan

Dr Sukartono Toposubroto SpPDRSI Pekajangan Pekalongan

Round Tabel DiscussionRSI Pekajangan

Round Tabel DiscussionRSI Pekajangan

Dyslipidaemia and CVD RiskDyslipidaemia and CVD Risk

Most cardiovascular events and deaths attributable to raised blood pressure and dyslipidaemia occur among patients with blood pressure and lipid concentrations deemed normal.

Intervention studies have confirmed the cardiovascular benefits of statins in primary prevention, secondary prevention and acute coronary syndromes across a wide age range and among patients with total cholesterol concentrations much lower than average.

The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome.

Conventional Risk Factors for Coronary Heart Disease

Conventional Risk Factors for Coronary Heart Disease

4 Risk Factors4 Risk Factors

CigaretteCigaretteSmokingSmoking

Hyper-Hyper-lipidemialipidemia

Hyper-Hyper-tensiontension DiabetesDiabetes

• 87% to 100% of patients who experienced a 87% to 100% of patients who experienced a fatal coronary event had an antecedent fatal coronary event had an antecedent exposure to exposure to 1 risk factor. 1 risk factor.**

• > 80% of patients with coronary disease had > 80% of patients with coronary disease had 1 of the 4 conventional risk factors.1 of the 4 conventional risk factors.****

* JAMA 2003;290:891 ** JAMA 2003;290:898* JAMA 2003;290:891 ** JAMA 2003;290:898

What is Dyslipidaemia?What is Dyslipidaemia?

Dyslipidemias are disorders of lipoprotein metabolism

Including lipoprotein overproduction & deficiency

They may manifest as one or more of the following: Elevated total cholesterol, low-density lipoprotein cholesterol (LDL), & triglyceride levels or as decreased high-density lipoprotein cholesterol (HDL) level

Cholesterol Biosynthetic Pathway

Lipid MetabolismLipid Metabolism Cholesterol synthesis

Lipoproteins:

VLDL

LDL

HDL

Chylomicrons

Apolipoproteins

LDL receptor

How to Assess Risk?How to Assess Risk?

• Assess risk factors:

CHD or CHD risk equivalent (regardless of number of risk factors) using NCEP ATP III definition of CHD & CHD risk equivalent

≥ 2 risk factors with no CHD & no CHD risk equivalent using NECP ATP III major risk factors that modify LDL goals

• If ≥ 2 risk factors & no CHD or CHD risk equivalent:

Assess global CHD risk by Framingham Point Score

CHD & CHD Risk EquivalentCHD & CHD Risk EquivalentClinical CHD Carotid artery

diseasePeripheral

arterial disease

Abnormal aortic

aneurysm

DM

Myocardial ischemia (angina)

Stroke history Claudication Present Present

Myocardial infarction Transient ischemic attack history

ABI > 0.9

Coronary angiography &/or stent replacement

Carotid stenosis > 50%

CABG

Prior unstable angina

Any of these present?

Yes -------------------------------------------- CHD or CHD risk equivalent

No ----- See if the patient has major risk factors that modify LDL goals

NCEP ATP III Definition of CHD & CHD Risk Equivalent

Major Risk Factors That Modify LDL GoalsMajor Risk Factors That Modify LDL Goals

Positive risk factors (↑ risk) Negative risk factors (↓ risk)

Age: Male ≥ 45 yrFemale ≥ 55 yr

High HDL (≥ 60 mg/dl)

Family history of premature CHD (definite MI or sudden death before 55 yr in father or other male first degree relative OR before 65 yr in mother or other female relative)

Current cigarette smoking

Hypertension (≥ 140/90 mm Hg or on antihypertensive drugs)

Low HDL (< 40 mg/dl)

NCEP ATP III Major Risk Factors That Modify LDL Goals

Check if your patient has ≥ 2 risk factors

Framingham Point ScoreFramingham Point Score

When to use it?

• If the patient has CHD or CHD risk equivalent

• ≥ 2 risk factors & no CHD or CHD risk equivalent

• < 2 risk factors

NO

Yes

NO

Framingham Point ScoreFramingham Point Score

• It defines the 10 year risk of developing CHD

• Framingham Point Score Male

• Framingham Point Score Female

How to Assess:How to Assess:

Your patient must fall in one of 3 categories:

• If the patient has CHD or CHD risk equivalent

• ≥ 2 risk factors & no CHD or CHD risk equivalent

• < 2 risk factors No need to use Framingham score

because these patients already have ≥ 20% risk

of CHD in 10 years without any calculation

Use to Framingham score to assess their 10 year

risk No need to use

Framingham score because they already have

low risk for CHD

Classification of Lipid LevelsClassification of Lipid Levels

Total cholesterol mg/dl LDL cholesterol mg/dl

< 200 Desirable < 100 Optimal

200-239Border line high

100-129Near optima/Above optimal

≥ 240 High

130-159Borderline high

160-189 High

≥ 190 Very high

NCEP ATP III Classification of Blood Lipids

Classification of Lipid LevelsClassification of Lipid Levels

Triglycerides mg/dl HDL cholesterol mg/dl

< 150 Normal

< 40 Low150-199

Border line high

200-400 High ≥ 60 High

≥ 500 Very high

NCEP ATP III Classification of Blood Lipids

Secondary Causes of Lipoprotein Abnormalities

Secondary Causes of Lipoprotein Abnormalities

Non Lipid Risk Factors for CHDNon Lipid Risk Factors for CHD

Modifiable Risk Factors Non Modifiable Risk Factors

Hypertension Age

Cigarette smoking Male

Thrombogenic/ hemostatic state Family history of premature CHD

Diabetes

Obesity

Physical inactivity

Atherogenic Diet

Treatment ModalitiesTreatment Modalities

Therapeutic Life Style Changes Therapeutic Life Style Changes

Nutrient Recommended intake

Total fat 25-35% of total calories

Saturated fate < 7% of total calories

Polyunsaturated fat Up to 10% of total calories

Monounsaturated fat Up to 20% of total calories

Carbohydrates 50-60% of total calories

Fiber 20-30 g/day

Cholesterol < 200 mg/day

Protein 15% of total calories

Therapeutic Life Style Changes Therapeutic Life Style Changes

Other life style changes include:

• Weight reduction specially in overweight patients (reduce 10% in the first 6 months)

• Increase physical activity

• Smoking cessation

Therapy Dose (g/day) Effect

Dietary soluble fiber 2-8 LDL-C 5-10%

Soy protein 20-30 LDL-C 5-7%

Stanol esters 1.5-4 LDL-C 10-15%

Dietary Adjuncts: Efficacy at Reducing LDL-CDietary Adjuncts: Efficacy at Reducing LDL-C

Jones PJ. Curr Atheroscler Rep 1999;1:230-235Lichtenstein AH. Curr Atheroscler Rep 1999;1:210-214Rambjor GS et al. Lipids 1996;31:S45-S49Ripsin CM et al. JAMA 1992;267:3317-3325

Approximate Mortality Reduction Potential of Drug Vs Lifestyle Interventions in Patients with

Coronary Disease*

Approximate Mortality Reduction Potential of Drug Vs Lifestyle Interventions in Patients with

Coronary Disease*

DrugDrug

LifestyleLifestyle

LowLow dosedose aspirinaspirin 18%18%StatinsStatins21%21%ßß Blockers

Blockers23%23%ACEACE Inhibitors

Inhibitors 26%26%

SmokingSmoking cessation

cessation35%35%

PhysicalPhysical activityactivity

25%25%ModerateModerate alcohol

alcohol20%20%

Combined lifestyle

Combined lifestyle changeschanges

45%45%

Iestra JA et al. Circ 2005;112:924Iestra JA et al. Circ 2005;112:924

Drug Therapy for DyslipidemiaDrug Therapy for Dyslipidemia

• Bile acid resins

• Ezetimibe

• Niacin

• Statins

• Fibric acid derivatives

• Fish oil

• Postmenopausal drug therapy

ATORVASTATIN : HMG-CoA Reductase Inhibitor ATORVASTATIN : HMG-CoA Reductase Inhibitor Mechanism of ActionMechanism of Action

AcetylCoA

HMG-CoA

Mevalonate Farnesylpyrophosphate

Squalene Cholesterol

Squalenesynthase

Dolichol

Farnesyl-transferase

Farnesylatedproteins

E,E,E-Geranylgeranylpyrophosphate

Geranylgeranylatedproteins

Ubiquinones

HMG-CoA Reductase

Inhibition of the Cholesterol Biosynthetic Pathway

ATORWIN 10 & 20

Clinical TrialsClinical Trials

Trial Intervention Initial LDL Change in LDL

CHD event reduction

Acute coronary syndrome patients

MIRACL Atorvastatin 124-72 ↓ 42% ↓ 26%

AVERT Atorvastatin 145-77 ↓ 42% ↓ 36%

Patients without evidence of CHD

ASCOT Atorvastatin 132-85 ↓ 31% ↓ 50%

Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA)

Sever PS et al. Lancet. 2003;361:1149-1158

0

1

2

3

4

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

Atorvastatin 90 mg/dl*

Placebo 126 mg/dl*

P=0.0005

Cum

ulat

ive

inci

denc

e of

M

I and

fata

l CH

D (

%)

Follow-up (yr)

36% RRR

*Post-treatment LDL-C level

CHD=Coronary heart disease, RR=Relative risk

ATORVASTATIN : Primary PreventionATORVASTATIN : Primary Prevention

10,305 patients with HTN randomized to atorvastatin (10 mg) or placebo for 5 years

Statins provide significant benefit in moderate- to high-risk individuals by lowering LDL-C levels below current goals

ATORWIN 10 & 20

0

5

10

15

Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Trial

ATORVASTATIN : Secondary PreventionATORVASTATIN : Secondary Prevention

17.4%

14.8%

RR=0.84, P=0.048

Com

bine

d ca

rdio

vasc

ular

ev

ent r

ate

(%)*

Weeks

*Includes death, MI resuscitated cardiac arrest, recurrent symptomatic myocardial ischemia requiring emergency rehospitalization.

4 8 12 160

Atorvastatin

Placebo

Schwartz GG et al. JAMA 2001;285:1711-1718

3,086 pts with an ACS randomized to atorvastatin (80 mg) or placebo for 16 weeks

Acute intensive treatment significantly reduces event rates

ATORWIN 10 & 20

Follow-up (months)

3 6 9 12 15 18 21 24 27 30

30

25

20

15

10

5

0

P =0.005

Rec

urre

nt M

I, ca

rdia

c de

ath,

U

A, r

evas

cula

rizat

ion,

or

stro

ke

16% RRR

Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT)—TIMI 22 Study

Atorvastatin

Pravastatin

ACS=Acute coronary syndrome, CV=Cardiovascular, MI=Myocardial infarction, UA=Unstable angina

Cannon CP et al. NEJM 2004;350:1495-1504

ATORVASTATIN: Secondary PreventionATORVASTATIN: Secondary Prevention

4,162 pts with an ACS randomized to atorvastatin (80 mg) or pravastatin (40 mg) for 24 months

Acute intensive treatment significantly reduces event rates

ATORWIN 10 & 20

Years

Maj

or

CV

Eve

nt*

(%

)

0 1 2 3 4 5 6

P<0.001

22% RRR

Treating to New Targets (TNT) Trial

Atorvastatin (10 mg)


CHD=Coronary heart disease, CV=Cardiovascular, MI=Myocardial infarction, RRR=Relative risk reduction


LaRosa JC et al. NEJM 2005;352:1425-35

*Includes CHD death, nonfatal MI, resuscitation after cardiac arrest, or stroke

0.00

0.05

0.10

0.15

10,001 patients with stable CHD randomized to atorvastatin (80 mg) or atorvastatin (10 mg) for 4.9 years

High-dose statins provide benefit in chronic CHD

ATORWIN 10 & 20

Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) Trial


Cum

ulat

ive

Haz

ard

(%)

Years Since Randomization

0 1 2 3 4 5

4

8

12

HR=0.89, P=0.07

Simvastatin (20 mg)


Pedersen et al. JAMA 2005;294:2437-2445

HR=Hazard ratio, MI=Myocardial infarction

*Includes coronary death, hospitalization for nonfatal acute MI, or cardiac arrest with resuscitation

8,888 patients with a history of acute MI randomized to atorvastatin (80 mg) or simvastatin (20 mg) for 5 years

High-dose statins provide a strong trend towards benefit after a MI

ATORWIN 10 & 20

ACS Patients: Major Coronary Events MI + CHD Death + Resuscitated Cardiac Arrest

ACS Patients: Major Coronary Events MI + CHD Death + Resuscitated Cardiac Arrest

Years Since Randomization

Cu

mu

lati

ve H

azar

d (

%)

0 1 2 3 4 50

4

8

12

16

20

HR = .66 (95% CI = 0.46, 0.95), P=.02

34% RRR

Simvastatin

Atorvastatin

Pedersen, Olsson, Cater et al. WCC, 2006

Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) Trial

ATORWIN 10 & 20

SUMMARYSUMMARY

– Lower is better• LDL• CRP • Triglycerides

– LDL cholesterol as a primary target of therapy– Studies showed that Atorvastatin proof was in

better CVD risk prevention – ATORWIN as new Atorvastatin can be as a

new choice with high quality product, right dose and right price

(and probably) higher is better for HDL

Thank youThank you

atorwin rtd 2014 dr sukartono

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