Transcript Updates on the Management of Dyslipidemia A Review of the

Updates on the Management of Dyslipidemia
A Review of the 2013 ACC/AHA Cholesterol Guidelines
Timothy Gladwell, Pharm.D., BCPS, BCACP
Associate Professor and Vice Chair
Department of Pharmacy Practice
Husson University School of Pharmacy
Faculty Disclosure
Tim Gladwell, PharmD, BCPS, BCACP does not
have any actual or potential conflicts of interest
in relation to this CE activity.
Learning Objectives
• At the conclusion of this session, participants
should be able to:
– Describe the major differences between the ATP-III
and the 2013 ACC/AHA cholesterol guidelines
– Discuss the groups of patients for whom statins are
recommended based on the new guidelines, and
explain the rationale for the recommendations
– Discuss controversies and unresolved issues
surrounding the new lipid guidelines
– Apply an evidence-based approach to the
management of patients with dyslipidemia
Patient Case – Mr. Jones
• 68-y/o white man - T2DM & HTN
• Medications
– Aspirin 81mg daily
– Metformin 500mg twice daily
– Lisinopril 10mg daily
• SH – no tobacco or alcohol;
regular exercise & DASH diet
• FH – no premature CAD
• BP 134/78mm Hg
Labs:
• Chol 168
• LDL 92
• HDL 37
• TG 195
• A1c 7.4%
Does Mr. Jones need treatment for dyslipidemia?
Review of ATP-III Guidelines
• National Cholesterol Education Program (NCEP)
• Developed by an expert panel for the National Heart,
Lung, and Blood Institute (NHLBI)
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First Adult Treatment Panel (ATP-I) released in 1988
ATP-II released in 1993
ATP-III released in 2001
Update to ATP-III released in 2004
Review of ATP-III Guidelines
• Treatment assessed through 9-step process
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Step 1: Obtain fasting lipid panel
Step 2: Identify CHD or CHD equivalents
Step 3: Determine presence of major risk factors for CHD
Step 4: Assess 10-year risk of CHD using Framingham
tables (if 2+ risk factors and no CHD or CHD equivalents)
Step 5: Determine risk category and LDL goals
Step 6: Initiate TLC if necessary
Step 7: Initiate drug therapy if necessary
Step 8: Identify presence of metabolic syndrome
Step 9: Treat elevated triglycerides or low HDL
ATP III Guidelines At A Glance. Available at
https://www.nhlbi.nih.gov/guidelines/cholesterol/atglance.pdf.
Accessed 8/25/14
Review of ATP-III Guidelines
• LDL goals based on risk categories
• Secondary (non-HDL) goals
ATP III Guidelines At A Glance. Available at
https://www.nhlbi.nih.gov/guidelines/cholesterol/atglance.pdf.
Accessed 8/25/14
Patient Case – Mr. Jones
• 68-y/o white man - T2DM & HTN
• Medications
– Aspirin 81mg daily
– Metformin 500mg twice daily
– Lisinopril 10mg daily
• SH – no tobacco or alcohol;
regular exercise & DASH diet
• FH – no premature CAD
• BP 134/78mm Hg
Labs:
• Chol 168
• LDL 92
• HDL 37
• TG 195
• A1c 7.4%
Does Mr. Jones need treatment for dyslipidemia?
Patient Case - Mr. Jones
• 68-year-old man with T2DM & HTN
– CHD equivalent (T2DM)
– Goal LDL<100
– Already at goal (statin not necessary)
ATP III Guidelines At A Glance. Available at https://www.nhlbi.nih.gov/guidelines/cholesterol/atglance.pdf.
Accessed 8/25/14
Patient Case - Mr. Jones
• 68-year-old man with T2DM & HTN
– Non-HDL level is above goal (131mg/dL)
– Reinforce therapeutic lifestyle changes
– May consider drug therapy for his ↓HDL/↑TG
BUT – WHAT’S THE EVIDENCE?
ATP III Guidelines At A Glance. Available at https://www.nhlbi.nih.gov/guidelines/cholesterol/atglance.pdf.
Accessed 8/25/14
Dyslipidemia in Diabetes
Representative Literature
• Statins for primary prevention
– Collaborative Atorvastatin Diabetes Study (CARDS)
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T2DM ages 40-75 with > 1 risk factor
Baseline LDL levels averaged ~118mg/dL
Randomized to atorvastatin 10mg or placebo
Stopped early with significant 37% ↓ in CV events
Consistent results regardless of baseline LDL level
– Similar findings in subgroups of other trials
• HPS, AFCAPS/TEXCAPS, MEGA
Colhoun HM et al. Lancet 2004;364:685-96.
Dyslipidemia in Diabetes
Representative Literature
• Agents for HDL/TG modification
– ORIGIN trial
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T2DM or pre-diabetes aged 50 or older
History of CAD or risk factors for CAD
Approximately ½ of the patients on statins at baseline
At baseline, LDL~112; HDL~46; TG~142
Randomized to 1g omega-3 fatty acids or placebo
No difference in death from CV cause between groups
– Similar findings with other trials
• ACCORD (fibrates), AIM-HIGH (niacin)
ORIGIN Trial Investigators. N Engl J Med 2012;367:309-18.
2013 AHA/ACC Cholesterol Guidelines
• Expert panels appointed by NHLBI in 2008
– Developed critical questions
– Identified highest-quality evidence
• Primarily RCTs and meta-analyses
• Partnered with AHA in 2013 to write
recommendations
• Graded according to quality of evidence
• Conflict of interest policies enforced
• Peer reviewed and endorsed by multiple
organizations
Stone NJ et al. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.
2013 AHA/ACC Cholesterol Guidelines
• Critical questions addressed by the review
– What is the evidence for LDL and non-HDL goals
for the primary and secondary prevention of
atherosclerotic cardiovascular disease?
– What is the impact on lipid levels, effectiveness, and
safety for specific cholesterol-modifying drugs in the
general population and in selected subgroups?
Stone NJ et al. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.
2013 AHA/ACC Cholesterol Guidelines
• Summary of key recommendations
– Encourage healthy lifestyle
– Consider statins for patient groups who have been
shown to benefit in clinical trials
– Utilize pooled cohort estimate equation to determine
10-year risk of ASCVD in primary prevention
– Assess risk of toxicity in susceptible patients
– Initiate statin at appropriate dose based on risk
– Monitor for adherence
– Little evidence for benefits with non-statin agents
Stone NJ et al. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.
2013 AHA/ACC Cholesterol Guidelines
• What about LDL goals?
– The panel found no evidence to support the treat-totarget paradigm
• No RCTs have compared different LDL goals
– Potential problems with treat-to-target strategy
• Under-treatment if LDL is already at goal
• Addition of non-statin drugs to achieve pre-specified
targets may increase risk without reducing ASCVD event
rates
• Treat-to-target may unnecessarily increase provider visits
and costs
Stone NJ et al. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.
2013 AHA/ACC Cholesterol Guidelines
• Four main statin benefit groups
ASCVD
LDL>190
Age 40-75 with
diabetes
LDL 70-189
• Age < 75 – High-intensity statin†
• Age > 75 – Moderate-intensity statin
• High-intensity statin
• 10-year risk >7.5% - High-intensity statin
• 10-year risk <7.5% - Moderate-intensity statin
Age 40-75 without
ASCVD or diabetes • Moderate- to high-intensity statin
10-year risk >7.5%
†Consider
moderate-intensity statin if high-intensity is
contraindicated, or if safety concerns are an issue
Stone NJ et al. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.
2013 AHA/ACC Cholesterol Guidelines
• No specific recommendation made for:
– Patients with NYHA Class II-IV heart failure
– Patients on maintenance hemodialysis
• In these patients, individualize decision by
considering:
– Potential reduction in ASCVD risk
– Drug-drug interactions
– Adverse effects of medication
– Patient preference
Stone NJ et al. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.
2013 AHA/ACC Cholesterol Guidelines
• Statin intensity†
Agent
Low-intensity
(↓ LDL <30%)
Moderate-intensity
(↓ LDL 30%-49%)
High-intensity
(↓ LDL >50%)
Atorvastatin
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10mg-20mg
40mg-80mg
Rosuvastatin
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5mg-10mg
20mg-40mg
Simvastatin
10mg
20mg-40mg
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Pravastatin
10mg-20mg
40mg-80mg
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Lovastatin
20mg
40mg
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Fluvastatin
20mg-40mg
80mg
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Pitavastatin
1mg
2mg-4mg
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†Daily
dose required to achieve stated LDL reductions
Stone NJ et al. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.
2013 AHA/ACC Cholesterol Guidelines
• Pooled Cohort Risk Assessment Equations
– Designed to replace Framingham risk scores
– Estimates 10-year and lifetime risk of ASCVD
• Includes fatal or nonfatal MI, fatal or nonfatal stroke
– 10-year risk calculator
• Input age, sex, race, TC, HDL, SBP, HTN drug use,
diabetes status, and smoking status
• Valid for age 40-79 African-American or non-Hispanic
white men and women
• Threshold is >7.5%
Stone NJ et al. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.
2013 AHA/ACC Cholesterol Guidelines
• Pooled Cohort Risk Assessment Equations
– Downloadable spreadsheet and web-based version
available at:
http://my.americanheart.org/cvriskcalculator
2013 AHA/ACC Cholesterol Guidelines
• Safety issues with statins
– Assess for patient characteristics that might predispose to adverse effects
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Impaired renal or hepatic function
History of previous statin intolerance or muscle disorders
Unexplained ALT elevations >3 times the ULN
Concomitant use of interacting drugs
Age > 75
– Consider use of lower-intensity statin if any of these
characteristics are present
Stone NJ et al. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.
2013 AHA/ACC Cholesterol Guidelines
• Monitoring of statins
– Baseline ALT prior to initiation
• Consider baseline CK in patients at risk for muscle disorders
• Routine ALT or CK levels not recommended unless
symptomatic
– Baseline fasting lipid panel
• Repeat in 4-12 weeks to assess therapeutic response and every
3-12 months if clinically warranted
• Reinforce adherence if response is less than expected
• Consider increasing intensity or addition of non-statin if unable
to achieve desired goals
• Dose may be decreased if 2 consecutive LDL <40
Stone NJ et al. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.
2013 AHA/ACC Cholesterol Guidelines
• Management of adverse effects
– Mild to moderate muscle symptoms
• Discontinue statin until muscle symptoms resolve
• Once symptoms resolve, re-challenge with a lower dose
• If symptoms resume, discontinue statin and re-challenge with
lower dose of different statin once symptoms abate
• Gradually titrate to target dose
• If symptoms don’t resolve after 2 months, assume it is not
statin-related and resume original statin
– New onset diabetes
• Reinforce lifestyle modifications
– Memory impairment
• Consider other potential causes before stopping statin
Stone NJ et al. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.
2013 AHA/ACC Cholesterol Guidelines
• The role of non-statin agents
– Limited evidence to support use of non-statin agents
– Consider use of non-statin agents in the following
situations:
• In addition to statins in high-risk patients with less than
anticipated response:
– Clinical ASCVD and age<75
– Baseline LDL>190
– Age 40-75 years with diabetes
• As monotherapy in at-risk patients who are completely
statin-intolerant
• In patients with severe elevations of triglycerides (>500)
Stone NJ et al. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.
Revisiting Mr. Jones
• 68-y/o white man - T2DM & HTN
• Medications
– Aspirin 81mg daily
– Metformin 500mg twice daily
– Lisinopril 10mg daily
• SH – no tobacco or alcohol;
regular exercise & DASH diet
• FH – no premature CAD
• BP 134/78mm Hg
Labs:
• Chol 168
• LDL 92
• HDL 37
• TG 195
• A1c 7.4%
Is he a candidate for a statin based on 2013 AHA guidelines?
Revisiting Mr. Jones
• 68-y/o man with T2DM and LDL 92
ASCVD
LDL>190
Age 40-75 with
diabetes
LDL 70-189
• Age < 75 – High-intensity statin†
• Age > 75 – Moderate-intensity statin
• High-intensity statin
• 10-year risk >7.5% - High-intensity statin
• 10-year risk <7.5% - Moderate-intensity statin
Age 40-75 without
ASCVD or diabetes • Moderate- to high-intensity statin
10-year risk >7.5%
†Consider
moderate-intensity statin if high-intensity is
contraindicated, or if safety concerns are an issue
Stone NJ et al. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.
Revisiting Mr. Jones
• 68-year-old man with T2DM & HTN
– Current LDL is 92mg/dL
– 10-year risk score is 35.9%
– High-intensity statin is recommended
2013 AHA/ACC Cholesterol Guidelines
• Clinical controversies
– Pooled Cohort CV Risk Calculators
• Estimates of 12 million to 45 million additional candidates
for statin therapy based on CV risk estimates
– Pencina* et al. estimated 87.4% of men and 53.6% of women ages
60-75 would now be eligible for statins
• Validation attempts have yielded conflicting results:
– Ridker† et al. found overestimation of risk by 75%-150% when
applied to data from the Women’s Health Study and the
Physician’s Health Study
– Muntner‡ et al. reported good results in actual vs. predicted 5year risks in a contemporary cohort of the REGARDS study
*Pencina
MJ et al. N Engl J Med 2014;370:1422-31.
†Ridker PM et al. Lancet 2013;382:1762-5.
‡Muntner P et al. JAMA 2014;311:1406-15.
2013 AHA/ACC Cholesterol Guidelines
• Clinical controversies
– Removal of LDL goals
• Concern over message this sends to patients and providers
– Cholesterol levels are no longer important?
• Role of LDL goals in patient motivation
– Do we need a target to support lifestyle changes/adherence
• Does a lack of RCT evidence = lack of benefit?
– Decades of clinical experience with “treat-to-target” strategy
• Effect on current performance measures
– Will quality assurance measures follow the new guidelines?
2013 AHA/ACC Cholesterol Guidelines
• Clinical controversies
– Management of other patient groups
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Age <40 or >75 years without clinical ASCVD?
10-year risk of 5%-7.5%?
LDL >160mg/dl or other primary hyperlipidemias?
Additional risk assessment may be necessary
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High sensitivity C-reactive protein
Ankle-brachial index
Coronary artery scores
Family history of premature CHD
Elevated lifetime risk of ASCVD
Summary of Key Differences
ATP-III
AHA/ACC
Basis for recommendations Expert opinion based on
pathophysiology,
observational, & RCT data
Evidence-based
recommendations based
on RCTs and systematic
reviews
Risk stratification
CHD equivalents, risk
factors, 10-year risk of MI
4 specific risk groups based
on benefits in clinical trials
Risk calculation
Framingham risk score
Pooled cohort equation
Goals of therapy
LDL & non-HDL levels
(stratified by risk)
Statin intensity
(% LDL reduction)
Role for monitoring
Fasting lipid panel to assess Fasting lipid panel to assess
achievement of goal
adherence/therapeutic
response
Role of non-statin agents
Encouraged use if needed
to achieve LDL or non-HDL
goal
Discourages use in most
patients because of lack of
evidence on improving
outcomes
2013 AHA/ACC Cholesterol Guidelines
• Applying this information to practice
– Remember that these are just guidelines
– Apply an evidence-based approach
– Consider your patient population
– Individualize treatments
– Discuss risks and benefits with the patient
– Include patient preferences in decision-making
Dissenting Opinions???
Jacobson TA et al. J Clin Lipidol 2014;8:473-88.
Anderson TJ et al. Can J Cardiol 2014;30:377-80.
AACE Member Alert. Available at
https://www.aace.com/sites/all/files/Member_Alert_Re_Guidelines_112113.pdf. Accessed 3/15/15.
Comparison to Other Guidelines
Criteria
AHA/ACC 2013
AACE 2012
NLA 2014
Evidence Base
RCT
Meta-analyses
All data
All data
Treatment targets
None
• LDL (primary)
• HDL, non-HDL, TG,
apo-B (secondary)
• Non-HDL and LDL
(primary)
• Apo-B (secondary)
Risk calculators
Pooled cohort
• With 2+ ASCVD RF
 Framingham
 Reynold’s Risk Score
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1° Drugs
Statins
Statins
Statins
2° Drugs
Limited to certain
situations
Recommended if goals
not met
Recommended if goals
not met
Stone NJ et al. J Am Coll Cardiol 2014;63(25 Pt B):2889-934.
Jellinger PS et al. Endocrine Practice 2012;18 (Supp 1):S1-S78.
Jacobson TA et al. J Clin Lipidol 2014;8:473-88.
With 2+ ASCVD RF
Framingham
Pooled cohort
30-year risk
Post-Lecture Question #1
Changes in the recommendations of the 2013
AHA/ACC cholesterol guidelines from those in the
ATP-III guidelines include:
1. Elimination of LDL and non-HDL treatment targets
2. Inclusion of a new Pooled Cohort ASCVD risk
estimation calculator
3. A decreased role for non-statin cholesterol lowering
agents
4. All of the above
Post-Lecture Question #2
Which of the following would be considered a
high-intensity statin regimen?
1.
2.
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4.
Atorvastatin 10 mg daily
Rosuvastatin 20mg daily
Simvastatin 40mg daily
Pravastatin 80mg daily
Post-Lecture Question #3
According to the 2013 AHA/ACC cholesterol
guidelines, which of the following patients would be
most suitable for initiation of a moderate-intensity
statin regimen?
1. A 65-year-old man with a previous myocardial infarction
2. A 45-year-old woman with Type 2 diabetes, an LDL of
95mg/dL, and an estimated 10-year risk of ASCVD of 9%
3. An 80-year-old woman with a previous history of ischemic
stroke
4. A 24-year-old man with familial hypercholesterolemia and an
LDL of 225mg/dL
Questions???
References
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National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). 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). Circulation 2002;106:3143421.
Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA
guideline on the treatment of blood cholesterol to reduce atherosclerotic risk in adults: a report of the
American College of Cardiology/American Heart Association task force on practice guidelines. J Am
Coll Cardiol 2014;63(25 Pt B):2889-934.
Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HAW, Livingstone SJ, et al. Primary
prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative
Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet
2004;364:685-96.
The ORIGIN Trial Investigators. N-3 fatty acids and cardiovascular outcomes in patients with
dysglycemia. N Engl J Med 2012;367:309-18.
Pencina MJ, Navar-Boggan AM, D’Agostino RB Sr, Williams K, Neely B, Sniderman AD, et al.
Application of new cholesterol guidelines to a population-based sample. N Engl J Med 2014;370:142231.
Ridker PM, Cook NR. Statins: new American guidelines for prevention of cardiovascular disease.
Lancet 2013;382:1762-5.
Muntner P, Colantonio LD, Cushman M, Goff DC Jr, Howard G, Howard VJ, et al. Validation of the
atherosclerotic cardiovascular disease pooled cohort risk equations. JAMA 2014;311:1406-15.