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?