dyslipdemia guidelines head to head

DYSLIPIDEMIA

CLINICAL GUIDELINES UPDATE

DR. MOHAMMAD DAOUDCONSULTANT ENDOCRINOLOGIST

KAMC-NGHA JEDDAH

THE AGENDA…

INTRODUCTION

RISK ASSESSMENT TOOLS

GUIDELINES : HEAD TO HEAD

MANAGEMENT : STATINS +/-

CONCLUSION

CARDIOVASCULAR DISEASE (CVD)

(CVD) = Disease of the heart and blood vessels caused by the process of atherosclerosis; Includes CHD; ACS/Angina, TIA/Stroke and PAD

The leading cause of death in many countries with significant cost implications

Though mortality from CVD is falling but morbidity appears to be rising

CARDIOVASCULAR DISEASE (CVD)

(CVD) predominantly affects people older than 50 years

Risk factors

Non-modifiable

AgeSex

Family history of CVDEthnic background

ModifiableSmoking

HTNDyslipidemia

DMSocial : Low income

and social deprivation

WHERE WE ARE WE NOW?FROM ….TO

Risk stratification based on Five major steps.

- Obtain Fasting Lipid profile- Identify CHD risk equivalents- Identify CHD risk factors- Calculate 10 year risk of CHD using Framingham risk score- Determine the risk category and goals of therapy.

NCEP ATP III GUIDELINES FOR RISK ASSESSMENT

1.Diabetes Mellitus

2.Symptomatic Carotid Artery Disease

3.Peripheral Arterial Disease

4.Abdominal Aortic Aneurysm

5.CRF with Cr > 1.5 or GFR< 60

6.Multiple risk factors with a 10 year risk of CHD> 20%

CHD RISK EQUIVALENTS

ATP III MAJOR CHD RISK FACTORS OTHER THAN LDL-C

• Cigarette smoking• Hypertension: BP 140/90 mm Hg or on antihypertensive

medication• Low HDL-C: 40 mg/dL (1.03mmol/L)*• Family history of premature CHD (1st-degree relative):

• Male relative age 55 years• Female relative age 65 years

• Age -Male 45 years

-Female 55 years

HDL-C 60 mg/dL (1.55mmol/L) = negative risk factor; Delete one risk factor.

ATP III: Updated LDL-C Goals, Treatment Cut-Points

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

<130 mg/dL(optional:<100 mg/dL)

<100 mg/dL(optional:<70 mg/dL)†

LDL-C Goal

130 mg/dL(100–129 mg/dL: consider drug options)

130 mg/dL‡Moderatelyhigh risk:2 risk factors(10-year risk 10%–20%)

100 mg/dL(<100 mg/dL: consider drug options)

100 mg/dL‡High risk:CHD or CHD risk equivalents*

(10-year risk >20%)

ConsiderDrug TherapyInitiate TLCRisk Category

*CHD risk equivalents: clinical manifestations of noncoronary forms of atherosclerotic disease (transient ischemic attacks or stroke of carotid origin >50% obstruction of a carotid artery), diabetes, and 2 risk factors with 10-year risk >20% for hard CHD.

†The optional LDL-C goal of <70 mg/dL is favored in those at very high risk (e.g., people with diabetes, smokers) as well as those with metabolic syndrome, acute coronary syndrome, high TG, and/or non–HDL-C <100 mg/dL.

‡Any person at high or moderately high risk with lifestyle-related risk factors is a candidate for TLC to modify these risk factors regardless of LDL-C level.

ATP III: Updated LDL-C Goals, Treatment Cutpoints (cont’d)

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

Risk Category LDL-C Goal Initiate TLCConsiderDrug Therapy

Moderate risk: 2 risk factors(10-year risk <10%)

<130 mg/dL 130 mg/dL 160 mg/dL

Lower risk:0–1 risk factor

<160 mg/dL 160 mg/dL 190 mg/dL(160–189 mg/dL:LDL-C–lowering drug optional)

Not modified in update

WHAT’S NEW ?

LIPIDS ADA 2014… WAS

To get specified LDL target Statin therapy should be added, regardless of baseline

lipid levels, for DM patients:- With overt CVD

-Without CVD who is > 40 years old and have ≥ 1 other CVD risk factors. (A)

An alternative therapeutic goal : Reduction in LDL cholesterol by 30–40% from baseline

(A)

Statins use is based on desired LDL-C Intensity lowering rather than LDL target number

Adjustment of intensity of statin therapy may be needed based on individual patient response to medication

(e.g., side effects, tolerability, LDL cholesterol levels). E

LIPIDS ADA 2015


If targets are not reached; Use combination therapy

No outcome studies; CVD outcomes or safety.

(E)

Combination therapy(statin/ fibrate and statin/niacin)

has not been shown to provide additional cardiovascular benefit above statin therapy alone

and is Not generally recommended

A

LIPIDS ADA 2015

2013 ACC/AHA GUIDELINES ON TREATMENT OF

BLOOD CHOLESTEROL TO REDUCE ATHEROSCLEROTIC CARDIOVASCULAR RISK IN

ADULTS

NICE CLINICAL GUIDELINE 181GUIDANCE.NICE.ORG.UK/CG181

NICE 2014

An update of existing National Institute for Health and Care Excellence (NICE) guidance (published in 2008)

STATINS INTENSITY CATEGORIES NICE VS ACC/AHA

NICE

low intensity 20% to 30%

medium intensity 31% to 40%

high intensity > 40%

ACC/AHA

low intensity <30%

medium intensity 30% to <50%

high intensity ≥ 50%

Targeting LDL Targeting non-HDL


An alternative therapeutic goal : Reduction in LDL cholesterol by

30–40% from baseline (A)

STATINS INTENSITY CATEGORIES OF LOWERING LDL –C NICE VS ACC/AHA

NICE - DYSLIPIDEMIA AND (CVD) STATINS INTENSITY

Modest potency statins

Rosuvastatin 5-10 mgAtorvastatin :10-20 mg Simvastatin : 20-40 mgFluvastatin -XL : 80 mg

High potency statins

Rosuvastatin 20-40 mg

Atorvastatin :40-80 mg

2013 ACC/AHA GUIDELINES ON TREATMENT OF

BLOOD CHOLESTEROL TO REDUCE ATHEROSCLEROTIC CARDIOVASCULAR RISK IN

ADULTS

≥ 7.5% ASCVD 10-years Risk

Download from : Google Play Store Search for : ASCVD Risk

Link: Calculatorhttps://play.google.com/store/apps/details?id=org.acc.cvrisk

NICE CLINICAL GUIDELINE 181GUIDANCE.NICE.ORG.UK/CG181

NICELIPID MODIFICATION

CARDIOVASCULAR RISK ASSESSMENT AND THE MODIFICATION OF BLOOD LIPIDS FOR THE PRIMARY AND SECONDARY PREVENTION OF CARDIOVASCULAR DISEASE

ISSUED: JULY 2014 LAST MODIFIED: SEPTEMBER 2014

NICE GUIDELINES-2014 DYSLIPIDEMIA AND (CVD)

Do not use a risk assessment tool for people

1-With pre-existing CVD

2-Familial hyper-cholesterolemia

3- With type 1 DM

4-With CKD ; e GFR < 60 ml/min/1.73 m2 and/or albuminuria

NICE GUIDELINES -DYSLIPIDEMIA AND (CVD)

IDENTIFYING AND ASSESSING (CVD) RISK

Use the QRISK2 risk assessment tool to assess CVD risk for the primary prevention of CVD in people (including type 2 DM)

older than 40 up to and including age 84 years (review on regular basis)

QRISK2 cannot be used in people over 84 years of age.


IDENTIFYING PEOPLE FOR FULL FORMAL RISK ASSESSMENTDIABETIC PATIENTS

The QRISK2 risk assessment tool

Calculator is available at

http://www.qrisk.org

Exclude common secondary causes of dyslipidemia before referral

(Ex:excess alcohol, uncontrolled DM, hypothyroidism, liver disease and nephrotic syndrome)

DYSLIPIDEMIA AND (CVD)

Include all of the following in the assessment:-Smoking status -Alcohol consumption-Blood pressure-Body mass index or other measure of obesity

-Total-C, HDL-C, non-HDL-C and triglycerides-HbA1c-Renal function and e-GFR-Transaminase level (ALT , AST )-TSH

NICE : LIPID MODIFICATION THERAPY FOR THE PRIMARY AND SECONDARY PREVENTION OF CVD

Lipid measurement and referral

A fasting sample is not needed

Measure a full lipid profile (Total-C , HDL – C , TAG ) and (non-HDL-C ) to achieve the best estimate of CVD risk

Clinical findingsLipid profile

Family history =The likelihood of a familial lipid disorder



Consider Familial hyper- cholesterolemia and investigate if they have:

1-Total-C > 7.5 mmol/L and2- Family history of premature CHD

Definite MI or sudden death affecting a first degree relative before age of 55 yrs (males) or 65 yrs (females)



Arrange for specialist assessment if Total –C > 9.0 mmol/L or a non-HDL C > 7.5 mmol/L

even in the absence of a first-degree F.Hx of premature CHD disease

Refer for urgent specialist review if a person has a triglyceride concentration of > 20 mmol/L (Exclude excess alcohol or poor glycemic control)

DYSLIPIDEMIA AND (CVD) PHARMACOLOGIC THERAPY FOR THE

PRIMARY AND SECONDARY PREVENTION OF CVD

Use drugs with evidence in clinical trials of a beneficial effect on CVD morbidity and

mortality

When a decision is made to prescribe a statin use a statin of high intensity and low acquisition cost

NICE GUIDELINES -DYSLIPIDEMIA AND (CVD)STARTING A STATIN

Decide after an informed discussion and assure patient’s knowledge about Pros/ Cons

=Individualized care

Stress the importance of TLC and consider the patient preferences, Co-morbidities,

poly-pharmacy, general frailty, and life Expectancy

LIPIDSRX RECOMMENDATIONS AND GOALS

Lifestyle modification (TLC) has been shown to Improve the lipid profile in patients with diabetes.

(A)

This include:- Reduction of saturated fat, trans fat, and cholesterol intake -Increase of n-3 fatty acids, viscous fiber and plant stanols / sterols

-Weight loss (if indicated); and increased physical activity


SECONDARY PREVENTION OF CVD

-Start statin Rx in people with CVD with Atorvastatin 80 mg (or equivalent)

Use a lower dose of atorvastatin if any of the following apply: Potential drug interactions High risk of adverse effects Patient preference

Do not delay statin in secondary prevention to manage modifiable risk factors Ex : Person has ACS


PRIMARY PREVENTION OF CVD-Estimate the level of risk using the QRISK2 (when indicated)

-Exclude secondary causes

Offer Atorvastatin 20 mg for the primary prevention of CVD to people who have a ≥ 10% (10-year) risk of developing CVD (estimated with QRISK2 ).


PRIMARY PREVENTION FOR PEOPLE WITH TYPE 2 DM

Offer Atorvastatin 20 mg for the primary prevention of CVD to people with type 2 DM who have a ≥ 10% (10-year) risk of developing CVD

Estimate the level of risk using the QRISK2 assessment tool


PRIMARY PREVENTION FOR PEOPLE WITH TYPE 1 DM

Offer statin treatment for the primary prevention of CVD to adults with type 1 DM who:

1- Are older than 40 years or have had DM for > 10 years or2- Have established nephropathy or have other CVD risk factors.

>>>>>>

Treat adults with type 1 DM with Atorvastatin 20 mg


PREVENTION OF CVD TO PEOPLE WITH CKD

Offer Atorvastatin 20 mg for the primary or secondary prevention of CVD to people with CKD

Increase the dose if a > 40% reduction in non-HDL cholesterol is not achieved and (e GFR ) is ≥ 30 ml/min/1.73 m2

Agree the use of higher doses with a renal specialist if e GFR is < 30 ml/min/ 1.73 m2.

DYSLIPIDEMIA AND (CVD)

STATINS EFFICACY , SAFETY , TOLERABILITY

DYSLIPIDEMIA AND (CVD)FOLLOW-UP OF PEOPLE STARTED ON STATIN TREATMENT

Measure Total-C, HDL-C and non-HDL-C in all people who have been started on high-intensity Statin treatment at 3 months of treatment and aim for > 40% reduction in non-HDL-C

If the non-HDL cholesterol is not reduced by > 40 % : Discuss adherence and timing of dose Optimize adherence to diet and lifestyle measures Consider increasing the dose (if started on less than atorvastatin 80 mg and the person is judged to be at higher risk because of comorbidities, risk score or using clinical judgment)

NICE ADVICE AND MONITORING FOR STATINS AE

.

Statins and pregnancy/lacttion

Potential teratogenicity

Stop Statins if pregnancy is a possibility

Stop Statins 3 months before any attempt to conceive and to not restart them until breastfeeding is finished


Advise people who are being treated with a Statin:

Do not stop statins because of an increase in blood glucose level or HbA1c.

STATINS IMPACT ON RISK OF DM / DM CONTROL

Up to 9-14 % risk of new onset DM is reported from different meta-analysis esp. with high doses; Such effect of statins remains modest

Both T1D and T2D:HbA1c was slightly higher in the group treated with statins

(7.53% v.s. 7.41% . Mean difference was 0.12%, (P=0.003).

CV events were reduced by 16% in the group treated with intensive statin ;The efficacy of statins in reducing CV outcomes in T2D is well-established and of major importance to offset such HbA1c changes

Use of statins in primary prevention in T2D should not be changed.


Statins and creatine kinase (CK)

1- Do not measure CK levels in asymptomatic people who are beingtreated with a statin

2- If patient has suggestive myopathy symptoms ( persistent generalized unexplained muscle pain, associated or not with previous lipid-lowering therapy) before or after start of a statinIf they have, measure creatine kinase (CK) levels


Statins and creatine kinase (CK)

3- If patient has suggestive myopathy symptoms measure (CK):If CK levels are > 5 times the ULN, re-measure it after 7 days. If CK levels are still 5 times ULN, do not start statin treatment

If CK levels are raised but < 5 times ULN, start statin treatment at a lower dose

4- If statin therapy was tolerated for > 3 months ; R/O other causes of muscle pain or weakness and raised CK


Statins and Liver Transaminases

1- Measure baseline liver transaminase enzymes (ALT or AST ) ,at baseline , 3 and 12 months of starting a statin -No more testing unless clinically indicated

2- Do not routinely exclude from statin therapy people who have liver transaminase levels that are raised but are < 3 times ULN

NICE INTOLERANCE OF STATINS

If a patient is un-able to tolerate a high-intensity statin; Treat with the maximum tolerated dose

NICE INTOLERANCE OF STATINS

Seek specialist advice (by telephone, virtual clinic or referral)

about options for treating people at high risk of CVD:

CKDType 1 diabetesType 2 diabetes

Genetic DyslipidemiaCVD, who are intolerant to 3 different statins

NICE ADVICE ON

OTHER LIPID LOWERING AGENTS /COMBINATIONS

NICE COMBINATION RX

Do not routinely offer Fibrates and Do not offer Nicotinic acid (niacin) or Bile acid sequestrants (anion

exchange resins) or omega-3 fatty acid compounds for the prevention of CVD to any of the following group of patients :

-Treated for primary prevention-Treated for secondary prevention

-With CKD-With type 1 DM-With type 2 DM

[new 2014]

NICE COMBINATION THERAPY FOR PREVENTING CVD

Ezetimibe treatment in addition to Statins should be considered

For people with primary hyper- cholesterolemia (heterozygous familial and non-familial hyper- cholesterolemia )

TAKE HOME MESSAGES

DYSLIPIDEMIA AND (CVD) TAKE HOME MESSAGES

Guidelines are GuidelinesShould not eliminate our clinical judgment

Patient centered personalized care Safest practice and

best shared-decision


Risk assessment tools High risk groups = No need to calculate Risk

All others : Risk calculator ;Not “eyeballing” them !!

Use (non-HDL-C) (=Total-C – HDL-C) rather than LDL-C ;No need to fast

Or Fasting lipid profile : LDL-C

1.ASCVD / CHD equivalent

2-Diabetes Mellitus

3-Severe Dyslipidemia –Familial

4-CKD

5- Risk calculator : over next 10yrs

HIGH CVD RISK GROUPS - SUMMARY

NICE VS ACC/AHA VS ATP-III

NICE

low intensity 20% to 30%

medium intensity 31% to 40%

high intensity > 40%

ACC/AHA

low intensity <30%

medium intensity 30% to <50%

high intensity ≥ 50%

Targeting LDL Targeting non-HDL

ATP-III

LDL target

Reduction in LDL-C

30–40%

from base line


Lipid-lowering drugs-Statins for primary and secondary prevention

-Use the highest tolerated dose -Combination Rx ?

Use simultaneously guidelines on other modifiable risk factors for CVD (like HTN , DM)

NICE GUIDELINES DYSLIPIDEMIA AND (CVD)

GUIDELINE DEVELOPMENT GROUP (GDG)

1-Use medium intensity statins for Primary preventionAtorvastatin 20 mg

2- Use high intensity statin for Secondary preventionAtorvastatin 80 mg

3- Do it safely Assess on regular basis for

tolerance and adverse effects

dyslipdemia guidelines head to head

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