Health Care, Education and Research www.billingsclinic.com
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
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Lipoprotein Metabolism
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Cholesterol Lowering Medication
Statins
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Cholesterol Lowering Medication
Cholesterol Absorption Inhibitor
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Cholesterol Lowering Medication
Bile Acid Sequestrant
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Cholesterol Lowering Medication
Niacin
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Cholesterol Lowering Medication
Fibrates
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Cholesterol Lowering Medication
Fish Oils
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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
• Question: Should we start treatment?
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
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
• 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
Adult Treatment Panel III
• 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)
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
• 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
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
• 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
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.
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
• 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?• 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%
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
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
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%
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
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
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
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
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
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
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
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
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
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
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?
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
Other Contentious Points
• No period for open comment/critique• Apparent lack of attempt to correlate with other
guidelines
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
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
• 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?
• 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