Session II

Report
Updated Cholesterol Management
Guidelines
Donald Brown, Pharm.D, BCACP
May 3rd, 2014
Health Care, Education and Research
www.billingsclinic.com
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
Image available at: http://pic.pimg.tw/mulicia/8a5d7405327f4b775ba83e725dff57f9.png
Cholesterol Lowering Medication
Cholesterol
Absorption
Inhibitor
Image available at: http://pic.pimg.tw/mulicia/8a5d7405327f4b775ba83e725dff57f9.png
Cholesterol Lowering Medication
Bile Acid
Sequestrant
Image available at: http://pic.pimg.tw/mulicia/8a5d7405327f4b775ba83e725dff57f9.png
Cholesterol Lowering Medication
Niacin
Image available at: http://pic.pimg.tw/mulicia/8a5d7405327f4b775ba83e725dff57f9.png
Cholesterol Lowering Medication
Fibrates
Image available at: http://pic.pimg.tw/mulicia/8a5d7405327f4b775ba83e725dff57f9.png
Cholesterol Lowering Medication
Fish Oils
Image available at: http://pic.pimg.tw/mulicia/8a5d7405327f4b775ba83e725dff57f9.png
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 inhibitors
Image 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?
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
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%
FAST FORWARD ABOUT 12YEARS
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 mg
Atorvastatin 10 – 20 mg
Atorvastatin 40 – 80 mg
Rosuvastatin 5 – 10 mg
Simvastatin 20 – 40 mg
Pravastatin 40 – 80 mg
Lovastatin 40 mg
Fluvastatin XL 80 mg
Simvastatin
10 mg
Fluvastatin
40mg BID
Pravastatin
10 – 20
Pitavastatin
2 –mg
4 mg
Lovastatin 20 mg
Fluvastatin 20 – 40 mg
Pitavastatin 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
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?
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
QUESTIONS/COMMENTS

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