Stephan Babirak, PhD, MD Stephan Babirak, PhD, MD Metabolic Leader - - PowerPoint PPT Presentation

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

• f 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

• LDL ≥

≥ ≥ ≥ 200 (with CHD)

• LDL ≥

≥ ≥ ≥ 300 (without CHD) Patients failing diet, drug therapy, or drug intolerant Medicare Criteria: INDICATIONS FOR LDL APHERESIS National Lipid Association Recommendations:

• LDL ≥

≥ ≥ ≥ 200 (non HDL ≥ ≥ ≥ ≥ 230) with 2 CV RF and high CV risk or Lp(a) ≥ ≥ ≥ ≥ 50

• LDL ≥ 1

≥ 1 ≥ 1 ≥ 160 (non HDL ≥ 1 ≥ 1 ≥ 1 ≥ 190) and very high risk with CHD, CVD, PVD or diabetes

• Selective removal of LDL-C, VLDL, Lp(a)

(Acutely lowered 73-83%)

• Little or no effect on other plasma

components (HDL, Albumin, IgG)

SUMMARY OF EFFECTIVENESS

• 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 0.9 0.8 0.7 0.6 Medication LDL-Apheresis

• f Patients

ny Event 0.6 0.5 0.4 0.3 0.2 0.1 1 2 3 4 5 6 7 8 9 10 11 Medication p = 0.0088 72% RR @ 6 yrs Years Proportion of Without Any

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 (n=25) Medication Only (n=11) Progression 8% (2) 64% (7)

* >0.67 mm changes in minimal lumen diameter (MLD) were defined as above threshold.

Nishimura et al. Atherosclerosis 1999;144:409-17

Progression 8% (2) 64% (7) Unchanged 76% (19) 36% (4) Regression 16% (4)

CHANGE IN CAG AND IVUS PARAMETERS

1.0 0.5

p=0.004 mm

2.0 1.0 Plaque Area

p=0.08 mm2

1.0

NS

1.0 2.0 3.0

NS

Lumen Area Vessel Area

mm2 mm2

3.0 MLD 2.0

• 0.5
• 1.0

Med LDL-A

• 1.0

Med LDL-A

• 2.0
• 1.0
• 2.0
• 1.0
• 2.0
• 3.0

Med LDL-A Med LDL-A

• 3.0
• 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!!