the position of statins in the new guideline suroto dept of neurology, fac of medicine, sebelas...

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 if uncontrlled




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


Yes

Yes

Yes

Yes

Yes

Yes

Yes

No

No

No

Estimated 10-y ASCVD risk >7.5%High 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%


10 year ASCVD Risk (%) for someone with optimal risk

factor ( Col E )


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



ClinicalASCVD


LDL-C > 190 mg/dL

DiabetesAge 40-75 y


Age 40-75 y








Yes

Yes

Yes

Yes

Yes

Yes

Yes

No

No

No

Estimated 10-y ASCVD risk >7.5%High-intensity statin


Cardiovascular risk

calculator

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%


10 year ASCVD Risk (%) for someone with optimal risk

factor ( Col E )


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 )



ClinicalASCVD


LDL-C > 190 mg/dL

DiabetesAge 40-75 y


Age 40-75 y



Moderate-intensity statinModerate-intensity statin





Yes

Yes

Yes

Yes

Yes

Yes

Yes

No

No

No


Cardiovascular risk

calculator

Case 3

22 year white male•LDL- cholesterol 195•SBP: 120•Not taking anti-hypertension meds•Non-diabetic•Non-smoker



ClinicalASCVD


LDL-C > 190 mg/dL

DiabetesAge 40-75 y


Age 40-75 y



Moderate-intensity statinModerate-intensity statin





Yes

Yes

Yes

Yes

Yes

Yes

Yes

No

No

No


No Cardiovascular

risk calculator

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

the position of statins in the new guideline suroto dept of neurology, fac of medicine, sebelas...

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