Upload
jasper-crawford
View
220
Download
1
Tags:
Embed Size (px)
Citation preview
THE POSITION OF
STATINS
IN THE NEW GUIDELINE
SurotoDept of Neurology, Fac of Medicine,
Sebelas Maret University
Stroke Risk Factors—Overview
Treatment OptionsCarotid endarterectomyAntiplatelet therapyAnticoagulation therapyAntihypertensive therapyAntidiabetic therapyLipid-lowering therapies
Unmodifiable Risk FactorsAge Male sexRaceFamily history of stroke/coronary heart
disease
Modifiable Risk FactorsSmokingDietSedentary lifestyleAlcohol/Drug abuseObesity Carotid artery diseaseAtrial fibrillation HypertensionDiabetes
Dyslipidemia
Goldstein LB et al. Stroke. 2001;32:280-299.
•Akira Endo and Masao Kuroda of Tokyo, Japan commenced research into inhibitors of HMG CoA reductase in 1971. •This team reasoned that certain microorganism may produce inhibitors of the enzyme to defend themselves against other organism.
•The first agent isolated was Mevastatin ( ML- 236 ). •The pharmaceutical company, Merck & Co showed an interest in the Japanese research in1976, and isolated Lovastatin(mevinolin, MK803), the first commercially marketed statin.
•Dr Endo was awarded the 2006 Japan Prize for his work on the development of statins.
HISTORY
Statins*Statins*Reduction in
chylomicron and
VLDL remnants,
IDL, LDL-C
1. Anti-inflammatory effects
2. Decreased thrombosis
3. Restore endothelial function
4. Maintain SMC functionLumen
Lipid core
Macrophages
Smooth muscle cells
Potential mechanisms of benefit of statins
Pleitrophic effect
Lipid lowering effect
HMG Co A reductase inhibitor
Potential Time Course of Statin Effects in CAD / ACS
* Time course established
Vulnerableplaques
stabilized
Endothelialfunctionrestored
Ischemicepisodesreduced
Cardiacevents
reduced*
LDL-C lowered*Inflammation
reduced
Weeks-MonthsHours-Days
Statin Evidence: Expanding Benefits
Acute coronary event
4S
CARE/LIPID
4 month
No history of CAD
3 month
t = 0
6 month
Stable CAD
Secondary preventionPrimary prevention
MIRACL
ASCOT-LLA
HPS
Unstable CAD
AFCAPS / TexCAPS/WOSCOPS
Statin in primary and secondary prevention trials ; The lower the better
With CHDevent (%)
50 70 90 110 130 150 170 190 210
0
5
10
15
20
25
LIPID-Rx
CARE-PBO
CARE-Rx
4S-RxLIPID-PBO
4S-PBO
AFCAPS-Rx
WOS-RxWOS-PBO
AFCAPS-PBO
LDL-C (mg/dL)
Secondary preventionPrimary prevention
PBO = PlaceboRx = Treated
HPS-PBO
HPS-RxTNT-PBO
TNT-Rx
NCEP - ATP Guidelines
LDL-C <70 mg/dL considered in extremely high risk patient. LDL-C lowering drug indicated in addition to TLC if LDL-C > 100 mg/dL The intensity of LDL-lowering drug tx in high – moderately high risk patients
must be sufficient to achieve at least 30-40% reduction in LDL levels
se emphasis on 1st prevention inclusion of high risk groups for 2nd prevention new risk levels for major lipid measures ( LDL-C <100 mg/dL optimal level for all
adults; HDL-C > 40 mg/dL and TG < 150 mg/dL ) Important secondary target were non-HDL-C in patient with TG > 200 mg/dL and metabolic syndrome New category “CHD risk equivalent” in diabetes and patients with > 20% CHD 10
year risk equivalent. Global risk score based on Framingham Heart Study used for calculation of 10 year risk
LDL-C target < 100 mg/dL Focus on 2nd Prevention Introduction of HDL-C as CHD risk ( <35 mg/dL )TG level<200 mg/dL was normal
LDL-C target < 130 mg/dL Focus on 1st Prevention
ATP - I
ATP - II
ATP - III
Revised ATP-III
1988
1993
2001
2004
The revised ATP-III was based on the review of
five statin trials conducted since the
release of ATP-III
TLC : Therapeutic Lifestyle Changes
ATP II ATP III
100 mg/dL< 100 mg/dL <70mg/dL in very high risk patients ( revised )
220 mg/dL 190 mg/dL
< 35 mg/dL < 40 mg/dL
200 mg/dL < 150 mg/dL
Risk Factor CHD Equivalent
No Yes
Total-C and HDL-C Total-C, HDL-C, LDL-C, and TG
LDL-C target for CHD or CHD Risk Equivalent :
LDL-C level in very high cholesterol :
Categorically low HDL-C :
Triglycerides :
Diabetes :Completion of Framingham
Risk Assessment :
Recommended lipidprofile :
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 1993;269:3015.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486.
Comparison of Major Features of ATP II and ATP III
ESC/EAS Guidelines
<1
>1 to <5
>5 to <10, or high risk
>10 or very high risk
No lipid intervention No lipid intervention Lifestyle intervention Lifestyle intervention
Lifestyle interventionLifestyle intervention
Lifestyle intervention,consider drug
Lifestyle intervention,consider drug
Lifestyle intervention,consider drug
Lifestyle intervention,consider drug if uncontrlled
Lifestyle intervention,consider drug if uncontrlled
Lifestyle intervention,consider drug if uncontrlled
Lifestyle intervention,consider drug if uncontrlled
Lifestyle intervention,and immediate drug intervention
Lifestyle intervention,and immediate drug intervention
Lifestyle intervention,and immediate drug intervention
Lifestyle intervention,and immediate drug intervention
Lifestyle intervention,and immediate drug intervention
Lifestyle intervention,and immediate drug intervention
Lifestyle intervention,and immediate drug intervention
Intervention strategies as a function of total CV risk and LDL-C level
ESC/EAS Guidelines for the management of dyslipidaemias
European Heart Journal (2011) 32, 1769–1818
ESC/EAS : European Society of Cardiology /European Atherosclerosis Society
< 1%
1%
2%
3-4%5-9%
10-14%
15% and over
10-year risk of fatal CVD in
populations at high CVD risk
SCORE+
European Heart Journal (2011) 32, 1769–1818
Total cardiovascular risk
estimation
1
2
3
4
5
Age
Risk will be higher than calculated in patients with additional conditions such as:
o Diabeteso Evidence of subclinical atherosclerosis (CalciumScore, Carotid Screening)o Familial premature atherosclerotic diseaseo Chronic Kidney Diseaseo Increased Lp (a), AboB/ApoB1 ratio, low HDL-C, high TC
• In patients at very high CV risk : established CVD, type 2 diabetes or type 1 diabetes with target organ damage, moderate to severe CKD or a SCORE level ≥10 % the LDL-C goal is <1.8 mmol/L(<~70 mg/ dL) and/or a ≥ 50 % LDL-C reduction when target level cannot be reached.
• In patients at high CV risk : markedly elevated single risk factors, a SCORE level ≥5 - <10% the LDL-Cgoal <2.5 mmol/L (<~100 mg/dL).
• In patients at moderate risk : SCORE level >1 to ≤5% the LDL-C goal <3.0 mmol/L (<~115 mg/dL).
If drug treatment is indicated to decrease LDL-C, a statin is recommended, up to the highest tolerable dose, to reach
the target level.
2013 ACC/AHA Guideline
2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic
Cardiovascular Risk in Adults November 12, 2013
Circulation,published online November 12, 2013
First new guidelines since ATP III guideline update in 2004
The most important statements or changes presented in these guidelines
• No longer have therapeutic targets• New risk calculator• Use medications proven to reduce risk, ie statins• Avoid medications or supplements that may lower the
cholesterol number, but have no data to decrease CV risk
Overview of the Expert Panel’s guideline
What has changed compared to ATP-III guideline?
Initiate either moderate-intensity or high-intensity statin therapy for patients who fall into the four categories
Unlike ATP-III, Do not titrate to a specific LDL cholesterol target
Measure lipids during follow-ups to assess adherence to treatment, not to achieve a specific LDL target
Four Major Statin Benefit Groups
1) Individuals with clinical ASCVD2) Individuals with LDL >1903) Individuals with Diabetes, 40-75 yo with LDL 70-
189 and without clinical ASCVD4) Individuals without clinical ASCVD or Diabetes,
with LDL 70-189 and estimated 10-year ASCVD risk >7.5%
ASCVD : AtheroSclerotic CardioVascular Disease
Age < 75y High-intensity statin
(Moderate-intensity if not candidate for high intensity Statin)
ClinicalASCVD
Adults age > 21y andA candidate for Statin Tx
LDL-C > 190 mg/dL
DiabetesAge 40-75 y
> 7.5% estimated 10-y ASCVD risk
Age 40-75 y
Estimate 10-y ASCVD riskWith Pooled Cohort Equation
Moderate-to- high intensity statin
Moderate-intensity statin
High-intensity statin(Moderate-intensity if not
candidate for high intensity Statin)
Age > 75y or if not candidate for high intensity Statin
Moderate-intensity statin
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
Estimated 10-y ASCVD risk >7.5%High intensity statin
Moderate-intensity statin
Cardiovascular risk
calculator
No Cardiovascular
risk calculator
Intensity of Statin Therapy
Circulation,published online November 12, 2013
High-Moderate-and Low-Intensity Statin Therapy (Used in the RCTs reviewed by the Expert Panel)
High-Intensity Statin Therapy
Moderate-Intensity Statin Therapy
Low-Intensity Statin Therapy
Daily dose lowers LDL-C on average, by approximately > 50%
Daily dose lowers LDL-C on average, by approximately 30% to 50%
Daily dose lowers LDL-C on average, by < 30%
Atorvastatin ( 40 )- 80 mgRosuvastatin 20 (40) mg
Atorvastatin 10 (20) mgRosuvastatin (5) 10 mgSimvastatin 20-40 mg*Pravastatin 40 (80) mgLovastatin 40 mgFluvastatin XL 80 mgFluvastatin 40 mg bidPitavastatin 2-4 mg
Simvastatin 10 mgPravastatin 10-20 mgLovastatin 20 mgFluvastatin 20-40 mgPitavastatin 1 mg
RCT : Randomized Control Trials
http://my.americanheart.org/cvriskcalculator
Risk Assessment :
1. Sex M or F
2. Age Years ( 40-79 )
3. Race AA ( Afro american ) or WH ( White or others )
4. Total Cholesterol mg/dL ( 130 - 320 )
5. HDL-Cholesterol mg/dL ( 20 – 100 )
6. Systolic blood pressure mmHg ( 90 – 200 )
7. Treatment for High blood pressure Y ( Yes ) or N ( No )
8. Diabetes Y ( Yes ) or N ( No )
9. Smoker Y ( Yes ) or N ( No )
Your 10 year ASCVD Risk (%)
10 year ASCVD Risk (%) for someone with optimal risk factor
( Col E )
Your lifetime ASCVD Risk (%)
Lifetime ASCVD Risk (%) for someone with optimal risk factor
( Col E )
Colum
n Char
t
This calculator only provides 10-year risk estimates for individuals 40-79
years of ageRisk Assessment :
STATIN Safety recommendations (1)
Select the appropriate dose If high or moderate intensity statin not tolerated, use
the maximum tolerated dose instead Conditions that could predispose patients to statin side
effect:• Impaired renal or hepatic function• History of previous statin intolerance or muscle disorder• Age >75• Unexplained ALT elevation > 3x ULN• History of hemorrhagic stroke• Asian ancestry
STATIN Safety recommendations (2)
Check baseline ALT prior initiating the statin (Grade B)
Check LFTs if patient develops Symptoms of hepatic dysfunction (Grade E)
If 2 consecutive LDL <40, Consider decreasing the statin dose (Grade C, weak recommendation)
It may be harmful to initiate simvastatin 80mg, or increase the dose of simvastatin to 80mg (Grade B)
Case 1
50 year old white female•Total cholesterol 180•HDL: 50•SBP: 130•taking anti-hypertension meds•+ diabetic•+ smoker
Calculated 10 yr ASCVD: 9.1%
Your 10 year ASCVD Risk (%)
10 year ASCVD Risk (%) for someone with optimal risk
factor ( Col E )
Your lifetime ASCVD Risk (%)
Lifetime ASCVD Risk (%) for someone with optimal risk
factor ( Col E )
9.1
0.8
50.0
Your 10 year ASCVD Risk
(%)
10 year ASCVD Risk (%) for
someone with optimal risk
factor ( Col E )
Your Lifetime ASCVD Risk
(%)
Lifetime ASCVD Risk
(%) for someone with optimal risk
factor ( Col E )
8.0
Age < 75y High-intensity statin
(Moderate-intensity if not candidate for high intensity Statin)
ClinicalASCVD
Adults age > 21y andA candidate for Statin Tx
LDL-C > 190 mg/dL
DiabetesAge 40-75 y
> 7.5% estimated 10-y ASCVD risk
Age 40-75 y
Estimate 10-y ASCVD riskWith Pooled Cohort Equation
Moderate-to- high intensity statin
Moderate-intensity statin
High-intensity statin(Moderate-intensity if not
candidate for high intensity Statin)
Age > 75y or if not candidate for high intensity Statin
Moderate-intensity statin
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
Estimated 10-y ASCVD risk >7.5%High-intensity statin
Moderate-intensity statin
Cardiovascular risk
calculator
High-Intensity Statin Therapy
Moderate-Intensity Statin Therapy
Low-Intensity Statin Therapy
Daily dose lowers LDL-C on average, by approximately > 50%
Daily dose lowers LDL-C on average, by approximately 30% to 50%
Daily dose lowers LDL-C on average, by < 30%
Atorvastatin ( 40 )- 80 mgRosuvastatin 20 (40) mg
Atorvastatin 10 (20) mgRosuvastatin (5) 10 mgSimvastatin 20-40 mg*Pravastatin 40 (80) mgLovastatin 40 mgFluvastatin XL 80 mgFluvastatin 40 mg bidPitavastatin 2-4 mg
Simvastatin 10 mgPravastatin 10-20 mgLovastatin 20 mgFluvastatin 20-40 mgPitavastatin 1 mg
Case 2
48 year white female•Total cholesterol 180•HDL: 55•SBP: 130•Not taking anti-hypertension meds•+ diabetic•Non-smoker
Calculated 10 yr risk ASCVD : 1.8%
Your 10 year ASCVD Risk (%)
10 year ASCVD Risk (%) for someone with optimal risk
factor ( Col E )
Your lifetime ASCVD Risk (%)
Lifetime ASCVD Risk (%) for someone with optimal risk
factor ( Col E )
1.8
0.7
39.0
8.0
Your 10 year ASCVD Risk
(%)
10 year ASCVD Risk (%) for
someone with optimal risk
factor ( Col E )
Your Lifetime ASCVD Risk
(%)
Lifetime ASCVD Risk
(%) for someone with optimal risk
factor ( Col E )
Age < 75y High-intensity statin
(Moderate-intensity if not candidate for high intensity Statin)
ClinicalASCVD
Adults age > 21y andA candidate for Statin Tx
LDL-C > 190 mg/dL
DiabetesAge 40-75 y
> 7.5% estimated 10-y ASCVD risk
Age 40-75 y
Estimate 10-y ASCVD riskWith Pooled Cohort Equation
Moderate-to- high intensity statin
Moderate-intensity statinModerate-intensity statin
High-intensity statin(Moderate-intensity if not
candidate for high intensity Statin)
Age > 75y or if not candidate for high intensity Statin
Moderate-intensity statin
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
Estimated 10-y ASCVD risk >7.5%High intensity statin
Cardiovascular risk
calculator
High-Intensity Statin Therapy
Moderate-Intensity Statin Therapy
Low-Intensity Statin Therapy
Daily dose lowers LDL-C on average, by approximately > 50%
Daily dose lowers LDL-C on average, by approximately 30% to 50%
Daily dose lowers LDL-C on average, by < 30%
Atorvastatin ( 40 )- 80 mgRosuvastatin 20 (40) mg
Atorvastatin 10 (20) mgRosuvastatin (5) 10 mgSimvastatin 20-40 mg*Pravastatin 40 (80) mgLovastatin 40 mgFluvastatin XL 80 mgFluvastatin 40 mg bidPitavastatin 2-4 mg
Simvastatin 10 mgPravastatin 10-20 mgLovastatin 20 mgFluvastatin 20-40 mgPitavastatin 1 mg
Case 3
22 year white male•LDL- cholesterol 195•SBP: 120•Not taking anti-hypertension meds•Non-diabetic•Non-smoker
Age < 75y High-intensity statin
(Moderate-intensity if not candidate for high intensity Statin)
ClinicalASCVD
Adults age > 21y andA candidate for Statin Tx
LDL-C > 190 mg/dL
DiabetesAge 40-75 y
> 7.5% estimated 10-y ASCVD risk
Age 40-75 y
Estimate 10-y ASCVD riskWith Pooled Cohort Equation
Moderate-to- high intensity statin
Moderate-intensity statinModerate-intensity statin
High-intensity statin(Moderate-intensity if not
candidate for high intensity Statin)
Age > 75y or if not candidate for high intensity Statin
Moderate-intensity statin
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
Estimated 10-y ASCVD risk >7.5%High intensity statin
No Cardiovascular
risk calculator
High-Intensity Statin Therapy
Moderate-Intensity Statin Therapy
Low-Intensity Statin Therapy
Daily dose lowers LDL-C on average, by approximately > 50%
Daily dose lowers LDL-C on average, by approximately 30% to 50%
Daily dose lowers LDL-C on average, by < 30%
Atorvastatin ( 40 )- 80 mgRosuvastatin 20 (40) mg
Atorvastatin 10 (20) mgRosuvastatin (5) 10 mgSimvastatin 20-40 mg*Pravastatin 40 (80) mgLovastatin 40 mgFluvastatin XL 80 mgFluvastatin 40 mg bidPitavastatin 2-4 mg
Simvastatin 10 mgPravastatin 10-20 mgLovastatin 20 mgFluvastatin 20-40 mgPitavastatin 1 mg
ASCVD : AtheroSclerotic CardioVascular Disease RCT : Randomized Control Trial
The statins (or HMG-CoA reductase inhibitors) form a class of Hypolipidemic drugs used to lower cholesterol levels in people with or at risk of Cardiovascular disease.
Based on clinical trials (RCT), the National Cholesterol Education Program / Adult Treatment Panel (NCEP-ATP) had developed guidelines, focus on aggressively lowering LDL-cholesterol.
The statins continue to play an important role in both the primary and secondary prevention of ASCVD.
End of 2013 the ACC and AHA , collaborate with the National Heart, Lung, and Blood Institute (NHLBI) develop new clinical practice guidelines for assessment of CV risk, lifestyle modifications to reduce CV risk, and management of blood cholesterol.
This guideline focuses on treatments to reduce ASCVD events.
Summary