2013 ACA/AHA Blood Cholesterol Guidelines

University of Southern California – Los Angeles County Hospital Journal Club

Thursday, January 23rd, 2014José 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/ • 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?• 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: • 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?

• 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

• 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?

• 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.