Health Care, Education and Research Updated Cholesterol Management Guidelines Donald Brown, Pharm.D,...

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Updated Cholesterol Management Guidelines

Donald Brown, Pharm.D, BCACP

May 3rd, 2014

Objectives

• Brief review of current and newer cholesterol lowering medications

• Discuss previous guidelines and how they compare to new guidelines

• Discuss controversy and treatment strategies

Pre-Lecture Questions

1. The updated cholesterol management guidelines address managing the statin intolerant patient.

– True or False

2. The updated cholesterol management guidelines risk calculator does not address patients less than 40 years old.

– True or False

3. Non-statin therapy has no place in managing patients’ cholesterol

– True or False

• The Art of James C. Christensen

Image available at: http://www.world-wide-art.com/images/James-Christensen/Low-Tech.jpg

Lipoprotein Metabolism

Image available at: http://pic.pimg.tw/mulicia/8a5d7405327f4b775ba83e725dff57f9.png

Cholesterol Lowering Medication

Statins



Cholesterol Absorption Inhibitor



Bile Acid Sequestrant



Niacin



Fibrates



Fish Oils


Current Arsenal

• Statins• Bile acid sequestrants• Ezetimibe• Fibrates • Niacin• Rx and OTC fish oil products• New

– Lomitapide (Juxtapib®) - MTTP inhibitor– Mypomersen (Kynamro®) – antisense

oligonucleotide

• Future? – PCSK9 inhibitors, CETP inhibitorsImage available at: http://www.3riversarchery.com/images/medium/6100X.jpg

Patient Case # 1

• 25 year old male with no medical history– No HTN, no DM, no smoking– Has a strong family history of premature CVD

• Father died of MI at age 42

– BMI = 25 kg/m^2– TC = 310 mg/dL– HDL-C = 50 mg/dL– TG = 400 mg/dL– LDL-C = 180 mg/dL

• Question: Should we start treatment?

Patient Case #2

• 64 year old male– No HTN, no DM, no smoking– SBP = 129 mmHg– TC = 180 mg/dL– HDL-C = 70 mg/dL– TG = 130 mg/dL– LDL-C = 84 mg/dL


SET THE WAY-BACK MACHINE

What Are We Used To?

• Adult Treatment Panel III Guidelines (2001)– Focused on:

• Primary prevention in patients with multiple risk factors

• Modifications of lipid classification

Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III): executive summary. National Cholesterol Education Program Web site. Available at: http://www.nhlbi.nih.gov/guidelines/ cholesterol/atp3xsum.pdf.

Adult Treatment Panel III

• Patients with multiple risk factors– Patients with diabetes without CHD

• Raised to CHD risk level

– Used Framingham risk projections– Patient with the Metabolic Syndrome

• Candidates for intensified TLC



• Modified lipid classifications– LDL-C < 100 mg/dL --- optimal– Raised categorical HDL-C

• < 35 mg/dL to 40 mg/dL

– Lowered TG classifications• Gives more attention to moderate elevations


• Supported implementing– Complete lipoprotein profile – Use of plant stanols and soluble fiber – Importance of adherence to TLC and medication

therapies– Identified importance of treating patients with TG

>200 mg/dL (Non-HDL-C)



• Primary Target: LDL-C– Goal based on CV risk

• Secondary Target: Non-HDL-C– When LDL-C goal met and TG ≥ 200 mg/dL– Goal is always the LDL-C goal + 30



• Secondary Prevention in patients with established CVD– LDL-C goal:

• 100 mg/dL, further reduction to 70 mg/dL

– If LDL-C < 70 mg/dL is not achievable due to high baseline• LDL-C reduction of 50% with statins and/or combination

1. Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III): executive summary. National Cholesterol Education Program Web site. Available at: http://www.nhlbi.nih.gov/guidelines/ cholesterol/atp3xsum.pdf.

2. Smith SC, Jr, et al. J Am Coll Cardiol. 2006;47:2130-2139.

Framingham Risk

• Framingham risk score– 10 year risk of developing coronary heart disease– Takes into account patient’s:

• Age• Gender• Total cholesterol value• Smoking status• HDL-C value• SBP and treatment status


A Word About Risk

• Risk factors– Formation of plaques– Cause plaques to rupture

• Major Risk Factors:– Cigarette smoking– Hypertension– Low HDL-C– Diabetes

Back to Patient Case # 1

• 25 year old white male with no medical history– No HTN, no DM, no smoking– Has a strong family history of premature CVD



• Question: Should we start treatment?• ATP III: 1 risk factor, Fram risk ~ 1%

Back to Patient Case #2

• 64 year old white male– No HTN, no DM, no smoking– SBP = 129 mmHg– TC = 180 mg/dL– HDL-C = 70 mg/dL– TG = 130 mg/dL– LDL-C = 84 mg/dL

• Question: Should we start treatment?• ATP III: Age, HDL – risk factor, Fram Risk 5%

FAST FORWARD ABOUT 12-YEARS

Many Trials/Papers Published

HPS IDEAL AIM-HIGH PROVE-IT

ACCORD HPS-THRIVE ASCOT-LLA JUPITER

VA-HIT PROSPER METEOR CARDS

ALLHAT-LLT ARBITER-2 SEARCH TNT

SHARP ENHANCE IMPROVE-IT HOPE-3

ACC/AHA Guidelines 2013

• Non-statin therapies de-emphasized• Emphasized lifestyle as the foundation

to risk reduction

2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: Available at: http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437738.63853.7a

What’s New?

1. Focus on ASCVD Risk Reduction: – 4 statin benefit groups

2. New perspective on LDL-C and/or Non-HDL-C treatment goals

3. Global risk assessment for primary prevention

4. Safety recommendations

5. Role of biomarkers and non-invasive tests


1. Four Statin Benefit Groups

• Four groups of primary and secondary prevention– Patients with clinical ASCVD– Patients with LDL-C ≥ 190 mg/dL– Patients with DM and no evidence of ASCVD

• 40 – 75 years old + LDL-C 70 – 189 mg/dL

– Patients w/o DM or ASCVD• LDL-C 70 – 189 mg/dL + 10-yrsk of ASCVD ≥ 7.5%


Origins of the Groups

• Randomized controlled trials– Who should get statin therapy and what intensity– Lowering of LDL-C 30 – 50% or more– Relative reduction in ASCVD risk consistent among

various patient groups

• Statin therapy reduces risk across spectrum of baseline LDL-C > 70 mg/dL


Defining Statin Intensity

• What are the statin intensity groups?– High intensity

• Lowers LDL-C ~ > 50%

– Moderate intensity• Lowers LDL-C ~ 30 to 50%

– Low intensity• Lowers LDL-C ~ < 30%

Rosuvastatin 20 – 40 mgAtorvastatin 40 – 80 mgAtorvastatin 10 – 20 mg

Rosuvastatin 5 – 10 mgSimvastatin 20 – 40 mgPravastatin 40 – 80 mgLovastatin 40 mgFluvastatin XL 80 mgFluvastatin 40mg BIDPitavastatin 2 – 4 mg

Simvastatin 10 mgPravastatin 10 – 20 mgLovastatin 20 mgFluvastatin 20 – 40 mgPitavastatin 1 mg

2. LDL “Goals” Perspective

• Paradigm shift– New perspective on treatment goals

• RCT evidence has only shown that ASCVD events are reduced by using the maximum tolerated statin dose

• The use of non-statin therapy– i.e. ezetimibe and niacin


LDL “Goals” Perspective

• Secondary prevention– Evidence only shows support for statin therapy to

maximally reduce LDL-C. • No support for a target

• FH w/ LDL-C > 190 mg/dL– May be difficult to achieve goal LDL-C < 100 despite

the use of 3 cholesterol-lowering medications• However, if patient achieves 50% reduction they are

receiving evidence based therapy


3. Global Risk Assessment

• Primary prevention– Use of a new pooled cohort equation– Identifying patients most likely to benefit– Who may not benefit

• Patient centered-approach– Risk reduction benefit, ADEs, DDIs and patient

preference


Risk Calculator

• Accounts for patient’s– Age, gender, ethnicity, SBP, …

Risk Calculator

Yes…There’s An App For That

4. Safety

• RCTs identified safety considerations– i.e Pre-diabetes

• Management of muscle symptoms• Use of pharmacists to aid in the safe use of

cholesterol lowering therapy

5. Biomarkers and Tests

• Role of biomarkers and non-invasive tests– Included recommendations to consider using

• LDL-C > 160 mg/dL• Evidence of genetic hyperlipidemias• Family history• hsCRP• CAC

CONTROVERSY

New Risk Calculator

• What was the equation/formula– Not yet provided– Not verified in prospective studies

• Of course, RCTs cannot available for every scenario – Should not mean a lack of evidence though

– Relies heavily on age and gender

More Patients on Statins

• 30 million more patients statin eligible• Younger than 40 years or older than 70

– May ignore treatment/prevention– May over treat primary prevention patient

• Lack of risk factors in calculator– Family history, CRP, Lp(a) or apoB

Raymond, C, Cho L, Rocco, M, Hazen SL. New Cholesterol Guidelines: Worth the Wait?. Cleveland Clinic Journal of Medicine.81(1).Jan 2014:11-19.O’Riordan M. New Cholesterol Guidelines Abandon LDL Targets. Available at: http://www.medscape.com/viewarticle/814152#1

Scatter plot with best-fit lines of major lipid trials (statin and nonstatin trials) for both primary and secondary prevention of coronary heart disease events.

RAYMOND C et al. Cleveland Clinic Journal of Medicine 2014;81:11-19

©2014 by Cleveland Clinic

Statin-intolerant Patients

• Recommend determine causal relationship with statin

• Investigate other possible causes• Stopping and re-starting statin therapy• Switch to another statin at a lower dose

• Truly intolerant statin?

Quality Measures

• What could this mean for quality measures– No targets, but insurance companies

• Is lack of LDL-C goals a flaw?• Necessary to repeat lipid levels?


Other Contentious Points

• No period for open comment/critique• Apparent lack of attempt to correlate with other

guidelines


Back to Patient Case # 1

• 25 year old male with no medical history– No HTN, no DM, no smoking– Has a strong family history of premature CVD




• According to new calculator– Risk calculator does not apply to him

• Less than 40 years old

– Even at 40 his 10-year risk is 3.1%– “Eligible” for statin therapy at 58 years– Comfortable waiting to start therapy?

• Of course you wouldn’t base decision solely on a risk calculator– If difficulty identifying patient for a statin group could

use other risks• History of premature atherosclerotic cardiovascular disease

in first degree relative• High sensitivity-reactive protein (CRP) > 2 mg/L• Coronary Artery Calcium (CAC) scan

Back to Patient Case #2

• 64 year old male– No HTN, no DM, no smoking– SBP = 129 mmHg– TC = 180 mg/dL– HDL-C = 70 mg/dL– TG = 130 mg/dL– LDL-C = 84 mg/dL

• Calculated risk = 7.5%

Patient Case #3

• 64 year old male– 2 pack per day smoker– Untreated HTN (SBP = 150 mmHg)– TC = 153 mg/dL– HDL-C = 70 mg/dL– TG = 60 mg/dL– LDL-C = 71 mg/dL

• Calculated risk = 10.5%

Summary

• There is controversy, but…• Should be treating diabetics more aggressively • TLC remains a cornerstone

Post-Lecture Questions

1. The updated cholesterol management guidelines address managing the statin intolerant patient.

– True or False

2. The updated cholesterol management guidelines risk calculator does not address patients less than 40 years old.

– True or False

3. Non-statin therapy has no place in managing patients’ cholesterol

– True or False

QUESTIONS/COMMENTS

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