How Low Should You Go

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How Low Should You Go?

• Managing Dyslipidemia Focus on ATP III
  Guidelines
• Tricia Williams, Pharm.D.

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Objectives

• Become familiar with the ATP III guidelines for
  hyperlipidemia management and be able to apply
  them to patient cases
• Recognize the recent changes in hyperlipidemia
  management guidelines
• Understand the risk factors and risk equivalents
  for CHD
• Know the recommendations for treatment of
  dyslipidemias in adolescents/children

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Hyperlipidemia At a Glance

• Leading risk factor for Coronary Heart Disease
  and Stroke
• May be primary or secondary
• Generally symptomless (unless severe)
• NHLBI Desirable lipid levels LDL Cholesterol

Sisson, EM Dyslpidemias Therapeutic Advances.
Pharmacotherapy Self-Assessment. 6th ed. 21-38.
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Who is at Risk?
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ATP III

• Adult Treatment Panel
• Developed by the NCEP (National Cholesterol
  Education Program), a project of the NHLBI
• Nine-step algorithm for the treatment of
  hyperlipidemia
• Revised in 2004 to include findings from five
  recent clinical trials

Grundy, SM, Cleeman, JI, Merz, CN, et al. for the
National Heart, Lung and Blood Institute,
American College of Cardiology Foundation, and
American Heart Association. Implications of
recent clinical trials for the National
Cholesterol Education Program Adult Treatment
Panel II guidelines. Circulation. 2004
110227-39.
6
ATP III

• Step 1
• Obtain lipoprotein levels (9-12 hr fast)
• LDL is the primary therapy target
• LDL
• Total Cholesterol
• HDL Cholesterol 40

New for ATP III
For full text of the ATP III guidelines, see
www.nhlbi.nih.gov/guidelines/cholesterol
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ATP III

• Step 2
• Determine CHD Risk Equivalents
• Clinical CHD
• Symptomatic carotid artery disease
• Peripheral artery disease
• Abdominal aortic aneurysm
• Diabetes
• Multiple risk factors and 10-year risk 20

Included as a Risk Equivalent for the first time
in ATP III
For full text of the ATP III guidelines, see
www.nhlbi.nih.gov/guidelines/cholesterol
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ATP III
Step 3 Determine CHD risk factors

• Smoking
• HTN
• Family hx
• Age men 45 women 55

HDL 60 removes one risk factor
For full text of the ATP III guidelines, see
www.nhlbi.nih.gov/guidelines/cholesterol
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ATP III

• Determination of Risk
• ATP Guidelines match the goal levels to absolute
  risk
• Reduction of composite risk long-term plus
  short-term
• Three identified risk categories CHD/CHD risk
  equivalent, Multiple (2) risk factors, 0-1 risk
  factor

For full text of the ATP III guidelines, see
www.nhlbi.nih.gov/guidelines/cholesterol
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ATP III

• Step 4
• 10-year risk assessment (for 2 risk factors)

• 20 (CHD risk equivalent
• 10-20

For full text of the ATP III guidelines, see
www.nhlbi.nih.gov/guidelines/cholesterol
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ATP III

• Step 5Determine Risk Category

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ATP III

• Step 6
• Initiate Therapeutic Lifestyle Changes
• TLC Diet Saturated fat fiber
• Weight management
• Increased physical activity

For full text of the ATP III guidelines, see
www.nhlbi.nih.gov/guidelines/cholesterol
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ATP III

• Step 7 Initiate drug therapy
• For CHD or CHD risk equivalent, consider drug and
  TLC simultaneously
• For other risk categories, consider adding drug
  to TLC after 3 months
• Handout Drug Therapy in Hyperlipidemia

For full text of the ATP III guidelines, see
www.nhlbi.nih.gov/guidelines/cholesterol
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Drug Treatment

• HMG-CoA Reductase Inhibitors, Statins
• LDL 18-55, HDL 5-15, TG 7-30
• ADRs Myopathy, LFTs
• Contraindications Liver disease
• Drug Interactions cyclosporine, macrolides,
  antifungals, CYP450 inhibitors

For full text of the ATP III guidelines, see
www.nhlbi.nih.gov/guidelines/cholesterol
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Drug Treatment

• HMG-CoA Reductase Inhibitors, Statins
• Good clinical evidence for use through clinical
  trials
• Reduce major coronary events, CHD deaths, need
  for coronary procedures , stroke, and total
  mortality

For full text of the ATP III guidelines, see
www.nhlbi.nih.gov/guidelines/cholesterol
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Drug Treatment

• Bile Acid Sequestrants
• LDL 15-30, HDL 3- 5, TG No effect
• Side effects GI upset, constipation
• Drug interactions can decrease absorption of
  multiple other drugs warfarin, digoxin,
  fluvastatin, ezetimibe

For full text of the ATP III guidelines, see
www.nhlbi.nih.gov/guidelines/cholesterol
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Drug Treatment

• Bile Acid Sequestrants
• CIs TGs 400 (possibly 200),
  dysbeta-lipoproteinemia
• Shown to reduce major coronary events and CHD
  deaths

For full text of the ATP III guidelines, see
www.nhlbi.nih.gov/guidelines/cholesterol
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Drug Treatment

• Nicotinic Acid (Niacin)
• LDL 5-25, HDL 15-35, TG 20-50
• Difficult to tolerate side effects flushing, GI
  upset, increase in uric acid, hyper-glycemia,
  hepatotoxicity
• Contraindications Gout, Chronic liver disease,
  diabetes, PUD
• Reduces major coronary events/total mortality(?)

For full text of the ATP III guidelines, see
www.nhlbi.nih.gov/guidelines/cholesterol
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Drug Treatment

• Fibric Acids (Fibrates)
• LDL 5-20, HDL 10-20, TG 20-50
• S/Es GI upset, Gallstones, Myopathy
• C/Is Severe renal or hepatic disease
• Reduced major coronary events
• Unexplained deaths in WHO study

LDL may actually increase if a patient has high
TGs
For full text of the ATP III guidelines, see
www.nhlbi.nih.gov/guidelines/cholesterol
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ATP III

• Step 8
• Identify and treat metabolic Sx
• Initiate after 3 months of TLC
• Treat underlying causes
• Weight management
• Increase physical activity
• Treat lipid and non-lipid risk factors
• Hypertension
• Aspirin, if indicated
• Treat elevated TGs and/or low HDL

For full text of the ATP III guidelines, see
www.nhlbi.nih.gov/guidelines/cholesterol
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ATP III

• Step 8 Identify and treat metabolic Sx

Any 3 or more of the following
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ATP III

• Step 9 Treat elevated triglycerides

For full text of the ATP III guidelines, see
www.nhlbi.nih.gov/guidelines/cholesterol
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ATP III
Step 9 Treat elevated triglycerides

• Primary goal is LDL within desired range
• Intensify weight management/increase physical
  activity
• For TGs 200 after LDL is reached, set a
  secondary goal non-HDL cholesterol no higher
  than 30 mg/dL than LDL goal

For full text of the ATP III guidelines, see
www.nhlbi.nih.gov/guidelines/cholesterol
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ATP III

• Consider adding medication therapy when
• Triglycerides remain 200-499 when LDL goal is
  reached
• Triglycerides are 500 mg/dL
• Fibrate or nicotinic acid

For full text of the ATP III guidelines, see
www.nhlbi.nih.gov/guidelines/cholesterol
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ATP III vs. ATP II

• Adds Diabetes as a risk equivalent
• Uses 10-year absolute risk assessments
  (Framingham tables)
• Identifies patients with metabolic syndrome as
  candidates for more aggressive TLCs
• Recommends total lipoprotein analysis

Grundy, SM, Cleeman, JI, Merz, CN, et al. for the
National Heart, Lung and Blood Institute,
American College of Cardiology Foundation, and
American Heart Association. Implications of
recent clinical trials for the National
Cholesterol Education Program Adult Treatment
Panel II guidelines. Circulation. 2004
110227-39.
26
ATP III vs. ATP II

• Plant sterols and soluble fiber as dietary
  recommendation
• Presents more comprehensive explan-ations of how
  to achieve TLCs
• LDL
• Low HDL is now defined as
• Recommends drug therapy for TGs 200

Grundy, SM, Cleeman, JI, Merz, CN, et al. for the
National Heart, Lung and Blood Institute,
American College of Cardiology Foundation, and
American Heart Association. Implications of
recent clinical trials for the National
Cholesterol Education Program Adult Treatment
Panel II guidelines. Circulation. 2004
110227-39.
27
Dyslipidemias in Children Adolescents

• Controversial Issues
• Who to Treat
• When to Treat
• Deciding to Use Prescription Medications
• Gathering of Data in a Young Population

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Children Adolescents

• Discovery and Confirmation of the Problem
• Autopsies on soldiers and accident victims (PDAY
  study Bogalusa Heart Study)
• Heart Transplants (Tuczu, et al)
• Postmortem examination of fetuses, infants, and
  children from hyper-cholesterolemic mothers
  (Napoli, et al)

• McCrindle, BW, Urbina, EM, Dennison, BA, et. Al.
  Drug Therapy of High-Risk Lipid Abnormalities in
  Children and Adolescents A Scientific Statement
  from the American Heart Association
  Atherosclerosis, Hypertension, and Obesity in
  Youth Committee, Council of Cardiovascular
  Disease in The Young, with the Council on
  Cardiovascular Nursing. Circulation. 2004 115
  (14) 1948-67.

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Dyslipidemias in Children Adolescents

• Discovery and Confirmation of the Problem
• Ultrasound
• Done in children with risk factors family
  history, diabetes, increased adiposity
• Assess intima thickness in carotid arteries
• Assess functionality of the arteries

• McCrindle, BW, Urbina, EM, Dennison, BA, et. Al.
  Drug Therapy of High-Risk Lipid Abnormalities in
  Children and Adolescents A Scientific Statement
  from the American Heart Association
  Atherosclerosis, Hypertension, and Obesity in
  Youth Committee, Council of Cardiovascular
  Disease in The Young, with the Council on
  Cardiovascular Nursing. Circulation. 2004 115
  (14) 1948-67.

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Children Adolescents

• Treatment Issues

• Universal cholesterol screening is not
  recommended
• Lack of evidence for long-term safety and
  efficacy of treatments
• Do not initiate in childhood for non-high risk
• Initiate treatment for high risk children
  (history of premature heart disease and/or
  parents with hypercholesterolemia)

• McCrindle, BW, Urbina, EM, Dennison, BA, et. Al.
  Drug Therapy of High-Risk Lipid Abnormalities in
  Children and Adolescents A Scientific Statement
  from the American Heart Association
  Atherosclerosis, Hypertension, and Obesity in
  Youth Committee, Council of Cardiovascular
  Disease in The Young, with the Council on
  Cardiovascular Nursing. Circulation. 2004 115
  (14) 1948-67.

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Children Adolescents

• Treatment Issues
• Guidelines focus on LDL cholesterol
• Drug treatment studies in children
• Have been limited
• Preliminary results show efficacy and safety
  similar to adults
• Limited to children and adolescents in high-risk
  categories

• McCrindle, BW, Urbina, EM, Dennison, BA, et. Al.
  Drug Therapy of High-Risk Lipid Abnormalities in
  Children and Adolescents A Scientific Statement
  from the American Heart Association
  Atherosclerosis, Hypertension, and Obesity in
  Youth Committee, Council of Cardiovascular
  Disease in The Young, with the Council on
  Cardiovascular Nursing. Circulation. 2004 115
  (14) 1948-67.

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Children Adolescents

• Treatment Issues
• Current treatment recommendations limited to bile
  acid-binding resins (cholestyramine and
  colestipol)
• Poor compliance
• Fat-soluble vitamin uptake
• Can cause TG increase
• Most statins have labeling for treatment of
  children

• McCrindle, BW, Urbina, EM, Dennison, BA, et. Al.
  Drug Therapy of High-Risk Lipid Abnormalities in
  Children and Adolescents A Scientific Statement
  from the American Heart Association
  Atherosclerosis, Hypertension, and Obesity in
  Youth Committee, Council of Cardiovascular
  Disease in The Young, with the Council on
  Cardiovascular Nursing. Circulation. 2004 115
  (14) 1948-67.

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Children Adolescents

• Non-Pharmacologic Treatments
• Low-fat, low-cholesterol diet
• Limit polyunsaturated fats
• Focus on balance and moderation
• Regular physical activity
• Other possibilities
• Omega 3s? Fiber? Garlic? Plant Sterols?

• McCrindle, BW, Urbina, EM, Dennison, BA, et. Al.
  Drug Therapy of High-Risk Lipid Abnormalities in
  Children and Adolescents A Scientific Statement
  from the American Heart Association
  Atherosclerosis, Hypertension, and Obesity in
  Youth Committee, Council of Cardiovascular
  Disease in The Young, with the Council on
  Cardiovascular Nursing. Circulation. 2004 115
  (14) 1948-67.

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Questions?

• St. Elizabeth Pharmacy ext. 6500
• tricia.williams_at_ssfhs.org