2013 ACA/AHA Blood
Cholesterol Guidelines
University of Southern California – Los Angeles County Hospital
Journal Club
Thursday, January 23rd, 2014
José L. González, MD
Outline
• Methodology
• Results
• Adverse effects and monitoring
• Discussion & Controversies
What’s New?
• No specific lipid treatment goals
• Limited scope; focus mainly on CQs
• New Pooled Cohorts Equation
• Focus on statins and statins only
Methodology
Organization of the Panel
• Appointed by the NHLBI
• 13 members, 3-ex members: primary care, cardiology, endocrinology,
experts in clinical lipidology, clinical trials cardiovascular epidemiology and
guideline development
• 16 members from NHLBI ATP IV panel
• 23 expert reviewers and representatives of federal agencies
Methodology
• Data from RCTs and meta-analyses of RCTs (1995-2009 + RCTs published
later)
• Rated fair to good quality by independent contractor
• Excluded poor quality RCTs, post-hoc analysis, observational studies
• Most studies excluded patients w/
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2° causes of hyperlipidemia
Triglycerides > 500
3 Critical Questions
• What is the evidence for LDL-C and non-HDL C goals for the SECONDARY
prevention of ASCVD?
• What is the evidence for LDL-C and non-HDL-C goals for the PRIMARY
prevention of ASCVD?
• What is the impact on lipid levels, effectiveness, and safety of specific drugs
used for lipid management in general and in selected subgroups?
Evidence Rating
• A: strong
• B: moderate
• C: weak
• D: recommend against
• E: expert recommendation
• N: no recommendation
Lifestyle modification
• Heart healthy diet
• Regular exercise
• Avoidance of tobacco products
• Maintenance of healthy weight
Secondary Causes of Hyperlipidemia
Results
Findings
• Statins prevent both non-fatal and fatal ASCVD events
• High level of evidence for secondary prevention
• Moderate level of evidence for primary prevention
• Statins and statins only
What was NOT found?
• Support for treatment to specific LDL and non-HDL goals
• Support for use of non-statin therapy (alone or in addition to statins)
• Support for the idea that lower cholesterol is better
• Reduced risk in patients on HD or w/ CHF
Use of non-statin therapy
• No evidence that it provides benefit, but…
• May consider it’s use in patients on max dose therapy or w/
contraindications to statin use
• Do not lower the dose of a statin to safely add a non-statin
4 groups that benefit
• Clinical ASCVD (includes TIA and stroke)
• LDL ≥ 190
• LDL between 70-190, but 40-75 yoa and DM
• LDL between 70-190, but 40-75 yoa and no DM
Statin Intensity
Pooled Cohorts Equation
• Used to estimate 10 yr risk of ASCVD
• Why not lifetime ASCVD risk?
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Lack of data on long-term f/u of RCTs 15 years
Limited safety data for > 10 years
Limited data on treatment of individuals < 40 yoa
Pooled Cohort Equation
• Why a cutoff of 7.5%?
• The higher your absolute risk, the greater your benefit
• Adverse events are independent of benefit, however
• Net benefit if ASCVD risk 5-7.5% w/ mod dose statin, but discuss w/ pt
Adverse Events
Adverse Effects of Statins
• New onset diabetes:
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0.1/100 for moderate intensity statins
0.3/100 for high intensity statins
• Myopathy: ~0.01/100
• Hemorrhagic stroke: 0.01/100
Recommendations before starting a statin
• Check baseline ALT, but no need to monitor
• No need to check baseline CK levels
• Don’t use in females of childbearing age unless using contraceptives
Monitoring Statin Theray
• Check initial fasting lipid panel
• Check follow-up 4-12 weeks after to determine adherence
• Perform assessments q 3-12 months as clinically indicated (?)
• Caveat: percent reduction of LDL not to be used as a treatment goal, but as
an indicator of response and adherence
Individuals w/ Predisposition to Adverse
Effects:
• Multiple comorbidities, (impaired hepatic or renal function)
• Hx of previous statin intolerance or muscle disorders
• Unexplained ALT elevations 3x ULN
• Concomitant use of drugs affecting statin metabolism
• >75 yoa
What to do in case of adverse events
• If muscle symptoms develop, stop statin, check CK, UA and Cr
• Eval for other causes
• If a causal relationship exists, switch statins
• Pregnancy category X
Discussion
& Controversies
Why not use specific goals?
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RCTs use fixed dose statins
Data = ASCVD events reduced by using max-tolerated intensity
LDL goals may result in under-tx, or over-tx w/ non-statin
AIM-HIGH – futility of adding niacin to pts w/ high triglycerides
ACCORD subgroup: fenofibrates in DM, needs further study + compare to statins
Familial hyperlipidemia may be unable to achieve goal, not necessarily tx failures
Type 2 DM = often have lower LDLs at baseline, under-tx
What about non-statins?
• Data do not show improved outcomes.
• Recommendations do include safety precautions when used.
• May be of use when patients cannot tolerate an indicated statin.
What about patients on HD or with CHF?
• No recommendation. Not even an E.
• 4 RCTs reviewed in these subgroups: no reduction in 2
• Insufficient evidence on which to base recommendations for or against
Individuals Already on a Statin
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if baseline LDL is unknown, an LDL < 100 was observed in most individuals
receiving high intensity statin (i.e. put them on high dose)
• RCT does support continuation of statins beyond 75-yoa in those already
tolerating them
What about other tests and biomarkers?
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CAC score
Non-HDL-C
Apo-B
LP(a) or LDL particles
Non-invasive testing
Lifetime ASCVD risk
ASCVD risk 5-7.5%
Strengths & Limitations
Strengths
• Most of the controversies arise from lack of data
• Strength of recs: doesn’t include specious recommendations, few grade E
• Limited to very high level of evidence
Limitations
• Patients <40 yoa have a low estimated 10-yr ASCVD risk score, thus don’t
qualify for treatment, yet they may have a high lifetime risk score
• No data on special subpopulations who are likely at high risk of ASCVD
(individuals w/ HIV, rheumatologic or inflammatory dz, s/p x-plant)
Future Directions
• Adults > 75 yoa
• Titration of meds to specific LDL goals
• Combination of submaximal statins w/ non-statins
• Management of hypertigylceridemias
• Use of other markers (apo-B, non-HDL, LP(a) or LDL particles,
Sources
• Keaney JF, Curfman GD, Jarcho J. “A Pragmatic View of the New Cholesterol
Treatment Guidelines.” N Engl J Med 2014; 370:275-278. January 16, 2014.
• Stone NJ, Robinson J, Lichtenstein AH et al “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.” J Am coll Cardiol. 2013;
90:’ doi:10.1016/j,jacc.2013.11.002.