Stephan Babirak, PhD, MD Stephan Babirak, PhD, MD Metabolic Leader Scarborough, ME
2013 ACC/AHA Risk Assessment and Cholesterol Treatment Guidelines Areas of Controversy • Inclusion of new calculator for 10-year risk for MI or stroke – Calculator validation in two external cohorts yielded c -statistics of 0.56-0.77 with systemic overestimation of risk – Calculator’s performance in 3 additional cohorts showed 75- 150% overestimation of risk 150% overestimation of risk – Future studies should clarify reasons for overestimation and evaluate refinement of the calculator Two recent trials do not support these data Martin, S and Blumenthal, R. Annals Internal Medicine 2014; 160: 356.
2013 ACC/AHA Risk Assessment and Cholesterol Treatment Guidelines Areas of Controversy • Abandonment of Lipid Goals – Guideline panel considered only selected randomized controlled trials and concluded that treatment targets are not evidence based • Consider selective use of LDL-C or non-HDL-C targets in high-risk adults • AIM-HIGH and ACCORD suggest possible benefit of add-on therapy for patients with high triglyceride levels and low HDL-C levels • Some experts maintain that lipid targets can enhance care when applied • Some experts maintain that lipid targets can enhance care when applied during follow-up in high-risk patients • Risk and lipid-based paradigms are not mutually exclusive and could be complementary – At baseline assess risk to determine whom to treat – At follow-up lipid measurements can serve as a marker of therapeutic response, promote adherence, motivate lifestyle improvements, and guide discussions about add-on therapy for patients at high risk Martin, S and Blumenthal, R. Annals Internal Medicine 2014; 160: 356.
National Lipid Association Recs • NonHDL/Apo B based approach • Reducing nonHDL reduces risk • RR adjusted to absolute risk • ASCVD begins early--consider intermediate and long term risk • ASCVD begins early--consider intermediate and long term risk • Statin is primary modality • Non-lipid ASCVD management Others: ADA, ANS, International Cardiology Recs
RCT Limitations • Statin based- LDL reduction only • Epidemology and Post Hoc analysis- adds additional considerations in some • Statin intolerance/submax dosing- ? guidance • Statin intolerance/submax dosing- ? guidance • Genetic issues- many not addressed • Age related- no data in < 40 or > 75 y/o • Population based- many questions unanswered, newer drugs not assessed and advised Lipid Clinic Referral for complex pts
Lipid Clinic Referral • Lifestyle and non-lipid options emphasized • Combination therapy expertise • DM Center of Excellence w CDE • Newer drugs- REMS • LDL Apheresis
MEDICATION TREATMENT • Statins – Decrease cholesterol synthesis • Bile-acid Resin – Increase cholesterol excretion • Cholesterol Absorption Inhibitor • Niacin – Multiple effects on LDL, HDL, Trigs, apoB • Mipomersen – Inhibitor of Apo B synthesis • Lomitapide – MTP inhibitor • PCSK-9 Inhibitor – Increase in LDL receptors
INDICATIONS FOR LDL APHERESIS Patients failing diet, drug therapy, or drug intolerant Medicare Criteria: • LDL ≥ ≥ 200 (with CHD) ≥ ≥ • LDL ≥ ≥ 300 (without CHD) ≥ ≥ National Lipid Association Recommendations: • LDL ≥ ≥ 200 (non HDL ≥ ≥ 230) with 2 CV RF and ≥ ≥ ≥ ≥ high CV risk or Lp(a) ≥ ≥ 50 ≥ ≥ • LDL ≥ 1 ≥ 1 60 (non HDL ≥ 1 ≥ 1 90) and very high ≥ 1 ≥ 1 ≥ 1 ≥ 1 risk with CHD, CVD, PVD or diabetes
SUMMARY OF EFFECTIVENESS • Selective removal of LDL-C, VLDL, Lp(a) (Acutely lowered 73-83%) • Little or no effect on other plasma components (HDL, Albumin, IgG) • Time average LDL-C lowering of 42-56% • Studies showed significant reductions of cardiovascular event rate • Improves Sxs
KAPLAN-MEIER CURVES SHOWING ALL CORONARY EVENTS IN PATIENTS WITH APHERESIS VS. MEDICATIONS 1 LDL-Apheresis 0.9 of Patients 0.8 ny Event 0.7 Medication Medication 0.6 0.6 Without Any Proportion of p = 0.0088 0.5 72% RR @ 6 yrs 0.4 0.3 0.2 0.1 0 0 1 2 3 4 5 6 7 8 9 10 11 Years Mabuchi et al. American Journal of Cardiology 1998;82:1489-1495
EFFECTS OF LDL-APHERESIS ON REGRESSION OF CORONARY ATHEROSCLEROSIS (L-CAPS) Frequency of Progression and Regression per Patient* LDL - Apheresis Medication Only (n=25) (n=11) Progression Progression 8% (2) 8% (2) 64% (7) 64% (7) Unchanged 76% (19) 36% (4) Regression 16% (4) 0 * >0.67 mm changes in minimal lumen diameter (MLD) were defined as above threshold. Nishimura et al. Atherosclerosis 1999;144:409-17
CHANGE IN CAG AND IVUS PARAMETERS Plaque Area MLD Lumen Area Vessel Area mm mm 2 mm 2 mm 2 p=0.08 NS NS p=0.004 1.0 2.0 3.0 3.0 2.0 2.0 0.5 1.0 1.0 1.0 0 0 0 0 -1.0 -1.0 -0.5 -1.0 -2.0 -2.0 -1.0 -2.0 -3.0 -3.0 Med LDL-A Med LDL-A Med LDL-A Med LDL-A M. Matsuzaki,et al., J Am Coll Cardiol 2002 ; 40: 220-227
SUMMARY • Reviewed national statin guidelines for population screening and treatment • Many controversies over individual patient care • Lipid management requires a patient centered approach • Metabolic Leader’s Lipid Clinic can help meet your patients’ needs in complex cases
Thank you!! Thank you!!
Recommend
More recommend
