Lipid Management Guidelines

Introduction to Lipid Targets

The European Society of Cardiology and the American Heart Association/American College of Cardiology have different recommendations for LDL-C targets, with the European Society of Cardiology recommending LDL-C <55 mg/dL for very high-risk patients, while the American Heart Association/American College of Cardiology recommends LDL-C <70 mg/dL as a threshold for adding non-statin therapies in very high-risk patients 1
Patients are categorized into four risk groups: very high, high, moderate, and low risk, considering both clinical ASCVD and subclinical ASCVD, with significant plaque on coronary angiography or CT angiography considered very high risk 1

Very high-risk patients should aim for LDL-C <55 mg/dL and ≥50% reduction from baseline, while high-risk patients should aim for LDL-C <70 mg/dL and ≥50% reduction (Class I) 1
Moderate-risk patients should aim for LDL-C <100 mg/dL (Class IIa), and low-risk patients should aim for LDL-C <116 mg/dL (Class IIb) 1, 2
Patients with recurrent vascular events within 2 years may consider LDL-C <40 mg/dL (Class IIb) 2
The American College of Cardiology recommends the following LDL-C goals based on risk category:
Risk Category LDL-C Goal
High-risk <100 mg/dL
Very high-risk <70 mg/dL (or optionally <55 mg/dL per newer guidelines)
Moderately high-risk <130 mg/dL
Lower-risk <160 mg/dL
3, 4, 5, 6, 7

Risk Category	LDL-C Goal
High-risk	<100 mg/dL
Very high-risk	<70 mg/dL (or optionally <55 mg/dL per newer guidelines)
Moderately high-risk	<130 mg/dL
Lower-risk	<160 mg/dL

For very high-risk ASCVD, consider adding non-statin therapy if LDL-C ≥70 mg/dL on maximally tolerated statin, with a treatment approach of starting with high-intensity statin therapy, then adding ezetimibe (Class I/B), and finally adding PCSK9 inhibitor if goal is still not achieved 1
For patients with baseline LDL-C ≥190 mg/dL not at goal with statin, add ezetimibe (Class IIa) 1
Ezetimibe, when combined with statins, provides an additional 25% reduction in LDL-C beyond statin therapy alone, by inhibiting the NPC1L1 protein in the small intestine, which reduces cholesterol absorption 8
PCSK9 inhibitor (evolocumab or alirocumab) is considered if LDL-C remains ≥2.6 mmol/L (≥100 mg/dL) despite high-intensity statin 9
Bempedoic acid is an additional option for patients not reaching goals 10
Combination therapy with ezetimibe and evolocumab is supported by guidelines for patients not at goal on monotherapy 11

The guidelines provide specific targets for non-HDL-C and apoB, with very high risk targets of non-HDL-C <85 mg/dL and apoB <65 mg/dL, high risk targets of non-HDL-C <100 mg/dL and apoB <80 mg/dL, and moderate risk targets of non-HDL-C <130 mg/dL and apoB <100 mg/dL 1
Non-HDL-C >100 mg/dL is considered a risk enhancer 1

The American College of Cardiology recommends the following dietary approaches to reduce cardiovascular risk:

Dietary Approach	Recommendation
Plant stanols/sterols	Reduce LDL-C by 7-15% as part of a comprehensive dietary approach
Saturated fat	<7% of total calories
Dietary cholesterol	<200 mg/day
Trans fats	<1% of energy
Mediterranean or DASH diet	Recommended pattern

Regular physical activity (≥150 minutes/week of moderate-intensity exercise), smoking cessation, and weight management (5-7% weight loss if overweight) are recommended by the American Heart Association, the American College of Cardiology, and the American Diabetes Association 14, 15, 16

Fasting lipid profile is reasonable for initial evaluation to aid in identifying familial lipid disorders, as recommended by the American College of Cardiology 18
Measuring apolipoprotein B is recommended if triglycerides are elevated (≥200 mg/dL), as suggested by the American College of Cardiology 18
The American College of Cardiology recommends checking LDL-C 4-12 weeks after initiating therapy or dose change, monitoring liver enzymes at baseline, 8-12 weeks after starting therapy or dose change, and monitoring for muscle symptoms and checking CK if symptoms develop 15
Measure lipid levels 4-6 weeks after initiating or changing therapy, and monitor annually once at goal, with more frequent monitoring (every 3-6 months) recommended for patients not at goal, as suggested by the American College of Cardiology 19, 18, 20, 11, 21, 22

High-intensity statin therapy should be initiated as early as possible during hospitalization for acute coronary syndrome, with lipid levels checked 4-6 weeks after ACS to determine if target is achieved, as suggested by the European Society of Cardiology 23
The European Society of Cardiology recommends high-intensity statins (atorvastatin 40-80mg, rosuvastatin 20-40mg) to reduce LDL-C by 50% or more and halt progression or contribute to regression of coronary atherosclerosis 23
Ezetimibe is not recommended in patients with moderate/severe hepatic impairment, and should be avoided during pregnancy due to limited safety data, as stated by the American College of Cardiology 8
The IMPROVE-IT trial demonstrated that ezetimibe added to simvastatin reduced cardiovascular events by 1.8% over 7 years (NNT: 56) 24
The FOURIER trial showed that evolocumab (PCSK9 inhibitor) decreased cardiovascular events by 1.5% over 2.2 years (NNT: 67) 24
The ODYSSEY OUTCOMES trial found that alirocumab (PCSK9 inhibitor) reduced cardiovascular events by 1.6% over 2.8 years (NNT: 63) 24