View
85
Download
1
Category
Preview:
Citation preview
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)
Atorvastatin (80 mg)
CHD=Coronary heart disease, CV=Cardiovascular, MI=Myocardial infarction, RRR=Relative risk reduction
ATORVASTATIN: Secondary PreventionATORVASTATIN: Secondary Prevention
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
ATORVASTATIN: Secondary PreventionATORVASTATIN: Secondary Prevention
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)
Atorvastatin (80 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
Recommended