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Shifts in Lipid Management: Who to treat, when to treat, target LDL?
Gregory R. Hartlage, MD
Southern Medical Group and Tallahassee Memorial
Hospital
Statin therapy
Stone N J et al. Circulation. 2014;129:S1-S45
Pre-statin evaluation
Stone N J et al. Circulation. 2014;129:S1-S45 Copyright © American Heart Association, Inc. All rights reserved.
Pre-statin evaluation
Effect of lipid-lowering therapy on triglyceride reduction
Secondary Causes of Hyperlipidemia
Stone N J et al. Circulation. 2014;129:S1-S45 Copyright © American Heart Association, Inc. All rights reserved.
Statin Intensity Classification
Stone N J et al. Circulation. 2014;129:S1-S45 Copyright © American Heart Association, Inc. All rights reserved.
Primary prevention
Goff D C et al. Circulation. 2014
• >20 yo – assess ASCVD risk factors and lifetime risk every 4-6 yr
• 40-79 yo – assess 10 year ASCVD risk every 4-6 yr
http://tools.cardiosource.org/ASCVD-Risk-Estimator/
http://tools.cardiosource.org/ASCVD-Risk-Estimator/
http://tools.cardiosource.org/ASCVD-Risk-Estimator/
Statin therapy for primary prevention
• LDL cholesterol >190 mg/dl at any age
– High-intensity statin
• Age 40-75 with DM
– 10 year risk ≥7.5% - high-intensity statin
– 10 year risk <7.5% - moderate-intensity statin
• Age 40-75 without DM
– 10 year risk ≥7.5% - moderate to high-intensity statin
– 10 year risk 5-7.5% - moderate-intensity statin
Primary Prevention - Novel markers and atypical risk factors?
• LDL>160/suggestion of genetic hyperlipidemia
• Family history of premature ASCVD (♂<55, ♀<65)
• HS-CRP≥2
• CAC≥300 or 75th percentile
• ABI<0.9
*Carotid IMT class III
*ApoB, Lp(a), PLA2 and LDL particle subfraction analysis – awaiting further research
• High-lifetime risk
– Inflammatory/rheumatic disease
– HIV/antiretroviral therapy
– S/p solid organ transplant (immunosuppressive therapy)
– Women with history of pre-ecclampsia and gestational HTN or DM
Novel markers?
Novel markers?
Secondary prevention
Statin therapy monitoring and optimization (targets?)
• Monitoring
– Lipid panel <12 weeks after initiation and dose adjustment; every 3-12
months therafter
– High-intensity: expect ≥50% reduction from baseline untreated LDL
– Moderate-intensity: expect 30-50% reduction from baseline untreated LDL
** ”LDL levels should not be used as performance standards”
• Insufficient response
– Medication and lifestyle adherence?
– Exclude secondary causes
– Consider non-statin therapies
Fixed dose statins versus LDL targets: Two ways of saying the same thing?
Moderate intensity
• Atorvastatin 10-20mg (TNT Trial)
– LDL 152 101 (mg/dl) = 34%
• Simvastatin 20-40mg (IDEAL Trial)
– LDL 155 104 (mg/dl) = 33%
• Lovastatin 20-40mg (AFCAPS/TexCAPS Trial)
– LDL 150 112 (mg/dl) = 25%
• Pravastatin 40-80mg (TIMI-22 Trial)
– LDL 106 83 (mg/dl) = 22%
Fixed dose statins versus LDL targets: Two ways of saying the same thing?
Moderate intensity
• Atorvastatin 10-20mg (TNT Trial)
– LDL 152 101 (mg/dl) = 34%
• Simvastatin 20-40mg (IDEAL Trial)
– LDL 155 104 (mg/dl) = 33%
• Lovastatin 20-40mg (AFCAPS/TexCAPS Trial)
– LDL 150 112 (mg/dl) = 25%
• Pravastatin 40-80mg (TIMI-22 Trial)
– LDL 106 83 (mg/dl) = 22%
Fixed dose statins versus LDL targets: Two ways of saying the same thing?
Moderate intensity
• Atorvastatin 10-20mg (TNT Trial)
– LDL 152 101 (mg/dl) = 34%
• Simvastatin 20-40mg (IDEAL Trial)
– LDL 155 104 (mg/dl) = 33%
• Lovastatin 20-40mg (AFCAPS/TexCAPS Trial)
– LDL 150 112 (mg/dl) = 25%
• Pravastatin 40-80mg (TIMI-22 Trial)
– LDL 106 83 (mg/dl) = 22%
Fixed dose statins versus LDL targets: Two ways of saying the same thing?
Moderate intensity
• Atorvastatin 10-20mg (TNT Trial)
– LDL 152 101 (mg/dl) = 34%
• Simvastatin 20-40mg (IDEAL Trial)
– LDL 155 104 (mg/dl) = 33%
• Lovastatin 20-40mg (AFCAPS/TexCAPS Trial)
– LDL 150 112 (mg/dl) = 25%
• Pravastatin 40-80mg (TIMI-22 Trial)
– LDL 106 83 (mg/dl) = 22%
Fixed dose statins versus LDL targets: Two ways of saying the same thing?
High-intensity
• Atorvastatin 80mg
– LDL 155 81 (mg/dl) = 49% (IDEAL Trial)
– LDL 152 77 (mg/dl) = 49% (TNT Trial)
– LDL 133 73 (mg/dl) = 45% (SPARCL Trial)
– LDL 106 52 (mg/dl) = 52% (TIMI-22 Trial)
• Rosuvastatin 20-40mg
– LDL 108 55 (mg/dl) = 50% (JUPITER Trial)
Fixed dose statins versus LDL targets: Two ways of saying the same thing?
High-intensity
• Atorvastatin 80mg
– LDL 155 81 (mg/dl) = 49% (IDEAL Trial)
– LDL 152 77 (mg/dl) = 49% (TNT Trial)
– LDL 133 73 (mg/dl) = 45% (SPARCL Trial)
– LDL 106 52 (mg/dl) = 52% (TIMI-22 Trial)
• Rosuvastatin 20-40mg
– LDL 108 55 (mg/dl) = 50% (JUPITER Trial)
Fixed dose statins versus LDL targets: Two ways of saying the same thing?
High-intensity
• Atorvastatin 80mg
– LDL 155 81 (mg/dl) = 49% (IDEAL Trial)
– LDL 152 77 (mg/dl) = 49% (TNT Trial)
– LDL 133 73 (mg/dl) = 45% (SPARCL Trial)
– LDL 106 52 (mg/dl) = 52% (TIMI-22 Trial)
• Rosuvastatin 20-40mg
– LDL 108 55 (mg/dl) = 50% (JUPITER Trial)
Fixed dose statins versus LDL targets: Two ways of saying the same thing?
High-intensity
• Atorvastatin 80mg
– LDL 155 81 (mg/dl) = 49% (IDEAL Trial)
– LDL 152 77 (mg/dl) = 49% (TNT Trial)
– LDL 133 73 (mg/dl) = 45% (SPARCL Trial)
– LDL 106 52 (mg/dl) = 52% (TIMI-22 Trial)
• Rosuvastatin 20-40mg
– LDL 108 55 (mg/dl) = 50% (JUPITER Trial)
LDL targets?
Other guidelines?
Statin safety
Laboratory monitoring
• Creatine kinase
– Only if at elevated risk or with muscle symptoms
• Transaminases
– Baseline, then only if symptoms arise
• Fasting glucose/Hgb A1c
– Per current screening guidelines for “at risk” population
• ≥2 LDL levels <40 mg/dl
– Decrease statin dose
Stone N J et al. Circulation. 2014;129:S1-S45
Muscle symptoms
• Obtain symptom history at baseline
• If new symptoms during treatment
– Discontinue and evaluate for:
• Hypothyroidism
• Renal and hepatic dysfunction
• Vitamin D deficiency
• Rheumatologic disorders
• Other causes of myopathy
– If symptoms resolve and no other cause identified/treated -> rechallenge
– If causal relationship identified -> rechallenge with low dose of alternative
statin once symptoms resolved
– If alternative cause identified -> rechallenge once condition adequately
treated Stone N J et al. Circulation. 2014;129:S1-S45
Statin Safety
• Moderate-intensity statins should be used in patients in whom
high-intensity would otherwise be recommended if:
– Age ≥75
– Low BMI
– Hepatic and/or renal impairment
– History of hemorrhagic stroke
– History of statin-related myalgias
– Use of other drugs affecting statin metabolism
– Asian ancestry
Stone N J et al. Circulation. 2014;129:S1-S45
Nonstatin therapy
Nonstatin therapy
• Statin intolerance
– Nonstatins that reduced
recurrent event rates
(*secondary prevention)
• Cholestyramine
• Niacin
• Omega-3
• Ezetimibe
• Add on to statin
therapies
– Additional benefit
• Ezetimibe
– No additional benefit
• Niacin
• Fenofibrate
(*all simvastatin 40-80mg)
Non-statin therapies and LDL targets revisited?
IMPROVE-IT Trial?
PCSK9 Inhibitors?
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