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/

• 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.