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.