Hyperlipidemia Management Guidelines
Foundation: Lifestyle Modifications for All Patients
Every patient with hyperlipidemia must begin with intensive lifestyle therapy regardless of pharmacologic treatment decisions. 1
- Adopt a Mediterranean or DASH dietary pattern emphasizing vegetables, fruits, whole grains, legumes, and non-tropical vegetable oils 1
- Limit saturated fat to <7% of total calories and completely eliminate trans fats 1
- Increase viscous fiber intake to 10-25 g/day and plant stanols/sterols to ~2 g/day 1
- Perform ≥150 minutes/week of moderate-intensity aerobic activity (or ≥75 minutes/week vigorous activity) 1
- Achieve 5-10% body weight loss if overweight or obese 1
Risk Assessment Algorithm
Step 1: Identify Automatic High-Intensity Statin Groups (No Risk Calculation Needed)
These patients require immediate high-intensity statin therapy without calculating 10-year ASCVD risk:
Clinical ASCVD (any age): Prior MI, ACS, stroke, TIA, PAD, or arterial revascularization → Start atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily 1
LDL-C ≥190 mg/dL (age ≥21 years): Severe primary hypercholesterolemia → Start high-intensity statin immediately 1
Diabetes + age 40-75 years + multiple ASCVD risk factors: Start high-intensity statin to achieve ≥50% LDL-C reduction 1
Step 2: Calculate 10-Year ASCVD Risk for Primary Prevention (Ages 40-75, No Diabetes, LDL-C 70-189 mg/dL)
Use the Pooled Cohort Equations to calculate 10-year ASCVD risk (available at http://tools.acc.org/ASCVD-Risk-Estimator-Plus) 1
| 10-Year ASCVD Risk | Statin Recommendation | Target LDL-C Reduction |
|---|---|---|
| ≥20% (High risk) | High-intensity statin | ≥50% reduction [1] |
| 7.5-19.9% (Intermediate risk) | Moderate-intensity statin; upgrade to high-intensity if risk-enhancing factors present | ≥30% reduction; ≥50% if upgraded [1] |
| 5-7.5% (Borderline risk) | Consider moderate-intensity statin only if risk-enhancing factors present | ≥30% reduction [1] |
| <5% (Low risk) | Lifestyle modification only; no statin indicated | N/A [1] |
Risk-Enhancing Factors (Use to Upgrade Statin Intensity)
If 10-year ASCVD risk is 7.5-19.9% (intermediate) or 5-7.5% (borderline), the presence of ANY of these factors favors initiating or intensifying statin therapy: 1
- Family history of premature ASCVD (male first-degree relative <55 years, female <65 years)
- Persistently elevated LDL-C ≥160 mg/dL (≥4.1 mmol/L)
- Chronic kidney disease (eGFR <60 mL/min/1.73 m²)
- Metabolic syndrome
- History of preeclampsia or premature menopause (age <40 years)
- Chronic inflammatory disorders (rheumatoid arthritis, psoriasis, HIV)
- Triglycerides ≥175 mg/dL
- High-sensitivity CRP ≥2 mg/L
- Ankle-brachial index <0.9
- Lipoprotein(a) ≥50 mg/dL
Coronary Artery Calcium (CAC) Scoring for Uncertain Cases
If the decision about statin therapy remains uncertain after risk calculation in intermediate-risk (7.5-19.9%) or selected borderline-risk (5-7.5%) adults, measure CAC score: 1, 2
- CAC = 0: Withhold statin therapy and reassess in 5-10 years (unless diabetes, family history of premature CHD, or smoking present) 1, 2
- CAC = 1-99: Initiate statin therapy for patients ≥55 years of age 1, 2
- CAC ≥100 or ≥75th percentile: Initiate statin therapy 1, 2
Statin Intensity Definitions and Specific Agents
High-Intensity Statins (≥50% LDL-C Reduction)
Moderate-Intensity Statins (30-49% LDL-C Reduction)
- Atorvastatin 10-20 mg daily 1
- Rosuvastatin 5-10 mg daily 1
- Simvastatin 20-40 mg daily 1
- Pravastatin 40-80 mg daily 1
Special Population: Diabetes Mellitus (Ages 40-75)
All diabetic adults aged 40-75 years require at least moderate-intensity statin therapy regardless of baseline LDL-C or calculated ASCVD risk (Class I, Level A recommendation). 1
- Start with moderate-intensity statin (atorvastatin 10-20 mg or rosuvastatin 5-10 mg) 1
- Upgrade to high-intensity statin if: 1
- Age 50-75 years
- Multiple ASCVD risk factors present
- 10-year ASCVD risk ≥7.5%
- Target: ≥50% LDL-C reduction with high-intensity; ≥30% with moderate-intensity 1
For diabetic patients >75 years already on statins: continue current therapy 1, 2
For diabetic patients >75 years not on statins: consider moderate-intensity statin after shared decision-making 1, 2
Adding Non-Statin Therapies
When to Add Ezetimibe (First-Line Add-On)
Add ezetimibe 10 mg daily when LDL-C remains ≥70 mg/dL on maximally tolerated statin in: 1
- Very high-risk ASCVD patients: History of multiple major ASCVD events OR 1 major ASCVD event + multiple high-risk conditions 1
- Diabetic patients aged 40-75 years with multiple ASCVD risk factors 1
- Primary hypercholesterolemia (LDL-C ≥190 mg/dL) when LDL-C remains ≥100 mg/dL on maximally tolerated statin 1
- 10-year ASCVD risk ≥20% when LDL-C reduction <50% on maximally tolerated statin 1
When to Add PCSK9 Inhibitors (Second-Line Add-On)
Add PCSK9 inhibitor (evolocumab or alirocumab) when LDL-C remains ≥70 mg/dL despite maximally tolerated statin + ezetimibe in: 1
- Very high-risk ASCVD patients 1
- Diabetic patients aged 40-75 years with multiple ASCVD risk factors 1
- Primary hypercholesterolemia (LDL-C ≥190 mg/dL) when LDL-C remains ≥100 mg/dL on statin + ezetimibe 1
Important caveat: Long-term safety (>3 years) is uncertain and cost-effectiveness is low at current prices. 1
Monitoring Protocol
| Timepoint | Action | Purpose |
|---|---|---|
| Baseline | Obtain fasting lipid panel (total cholesterol, LDL-C, HDL-C, triglycerides) [1] | Establish baseline for calculating % reduction |
| 4-12 weeks after initiation or dose change | Repeat lipid panel [1] | Verify adequate LDL-C reduction (≥30% for moderate-intensity, ≥50% for high-intensity) and assess adherence |
| Annually thereafter | Lipid panel [1] | Monitor sustained lipid control and detect non-adherence |
Clinician-Patient Shared Decision-Making Checklist
Before initiating statin therapy in primary prevention (ages 40-75), conduct a risk discussion that includes: 1
- Review of major risk factors (smoking, blood pressure, LDL-C, HbA1c if indicated, calculated 10-year ASCVD risk) 1
- Presence of risk-enhancing factors 1
- Potential benefits of lifestyle and statin therapies 1
- Potential for adverse effects and drug-drug interactions 1
- Out-of-pocket costs and insurance coverage 1
- Patient preferences and values 1
Critical Pitfalls to Avoid
- Do not withhold statin therapy in diabetic patients aged 40-75 years based on "normal" baseline LDL-C—the indication is based on diabetes diagnosis and age, not cholesterol level 1
- Do not use low-intensity statins in any patient—they are not recommended at any age 1
- Do not discontinue statins based solely on age in patients >75 years—cardiovascular benefits persist and absolute risk reduction is greater due to higher baseline risk 1, 2
- Do not calculate 10-year ASCVD risk for patients with LDL-C ≥190 mg/dL or established ASCVD—they require immediate high-intensity therapy 1
- Do not delay statin initiation while pursuing lifestyle modification alone—statins should be added to, not replace, lifestyle therapy 1
- Do not fail to consider ezetimibe before PCSK9 inhibitors—ezetimibe is preferred due to lower cost and proven cardiovascular benefit 3, 4