Management of Dyslipidemia in Adults
All adults with dyslipidemia should begin with intensive lifestyle modification and statin therapy, with intensity determined by age, diabetes status, presence of ASCVD, and 10-year cardiovascular risk—not by baseline LDL cholesterol levels alone. 1
Initial Assessment and Risk Stratification
- Obtain a fasting lipid panel (total cholesterol, LDL-C, HDL-C, triglycerides) at diagnosis, before initiating therapy, and annually thereafter once on treatment 1, 2
- For adults <40 years not on lipid-lowering therapy, repeat lipid panels every 5 years or more frequently if risk factors emerge 1
- Calculate 10-year ASCVD risk using the Pooled Cohort Equations for adults without diabetes or established ASCVD to guide treatment intensity 1, 3
Lifestyle Modifications (Foundation for All Patients)
Implement immediately and continue alongside pharmacotherapy:
- Dietary pattern: Adopt Mediterranean or DASH eating pattern emphasizing vegetables, fruits, whole grains, legumes, and nontropical vegetable oils 1
- Reduce saturated fat to <7% of total calories and eliminate trans fats entirely 1, 2
- Increase dietary components: Add viscous fiber (10-25 g/day from oats, legumes, citrus), plant stanols/sterols (2 g/day), and omega-3 fatty acids 1, 2
- Physical activity: Engage in at least 150 minutes per week of moderate-intensity aerobic exercise or 75 minutes of vigorous-intensity activity 1, 2
- Weight management: Pursue weight loss if overweight or obese 1
Statin Therapy Algorithm
Primary Prevention (No ASCVD)
Diabetes Patients:
Age 40-75 years with diabetes: Initiate high-intensity statin therapy to achieve ≥50% LDL-C reduction and target LDL-C <70 mg/dL (<1.8 mmol/L) if one or more additional ASCVD risk factors present (hypertension, smoking, chronic kidney disease, albuminuria, family history of premature ASCVD) 1
Age 40-75 years with diabetes but no additional ASCVD risk factors: Use moderate-intensity statin therapy 1
- Moderate-intensity options: atorvastatin 10-20 mg, rosuvastatin 5-10 mg, simvastatin 20-40 mg, pravastatin 40-80 mg daily 1
Age 20-39 years with diabetes and additional ASCVD risk factors: Consider initiating statin therapy after risk discussion 1
Age >75 years with diabetes: If already on statin, continue current regimen; if initiating new therapy, consider moderate-intensity statin after shared decision-making discussion 1
Non-Diabetes Patients:
LDL-C ≥190 mg/dL (≥4.9 mmol/L): Initiate high-intensity statin immediately regardless of age or calculated risk, aiming for ≥50% LDL-C reduction 1, 3, 4
10-year ASCVD risk ≥7.5% to <20% (intermediate risk): Initiate moderate-intensity statin to reduce LDL-C by 30-49%; consider high-intensity if risk-enhancing factors present (family history of premature CHD, chronic kidney disease, metabolic syndrome, persistently elevated triglycerides ≥175 mg/dL, inflammatory conditions) 1, 2
10-year ASCVD risk ≥20% (high risk): Use high-intensity statin to achieve ≥50% LDL-C reduction 1, 2
10-year ASCVD risk 5% to <7.5% (borderline risk): Consider moderate-intensity statin only if risk-enhancing factors present; may use coronary artery calcium score to guide decision (if CAC score ≥100 or ≥75th percentile, initiate statin) 1
Secondary Prevention (Established ASCVD)
- All ages with established ASCVD: Prescribe high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) regardless of baseline LDL-C 1, 3
- Target: LDL-C <70 mg/dL (<1.8 mmol/L) and ≥50% reduction from baseline 1, 2
- If high-intensity statin not tolerated, use maximum tolerated statin dose rather than discontinuing 1
Adding Non-Statin Lipid-Lowering Therapy
Ezetimibe (First-Line Add-On)
Add ezetimibe 10 mg daily when:
- LDL-C remains ≥70 mg/dL on maximally tolerated statin in patients with diabetes aged 40-75 years at higher cardiovascular risk 1
- LDL-C remains ≥70 mg/dL on maximally tolerated statin in patients with established ASCVD (very high risk) 1
- 10-year ASCVD risk ≥20% and LDL-C reduction <50% on maximally tolerated statin 1, 2
- Expected additional LDL-C reduction: 15-25% 2, 4, 5
PCSK9 Inhibitors (Second-Line Add-On)
Add PCSK9 inhibitor (evolocumab or alirocumab) when:
- LDL-C remains ≥70 mg/dL despite maximally tolerated statin plus ezetimibe in very high-risk patients with established ASCVD 1
- Patients with diabetes aged 40-75 years at higher cardiovascular risk with multiple ASCVD risk factors and LDL-C ≥70 mg/dL on maximally tolerated statin 1
- Expected additional LDL-C reduction: 50-60% when added to statin therapy 2, 5, 6
- Note: PCSK9 inhibitors provide substantial benefit in very high-risk and high-risk patients but offer little benefit in moderate or low cardiovascular risk groups 5
Bempedoic Acid (Statin-Intolerant Patients)
- For patients with diabetes intolerant to statin therapy, use bempedoic acid as an alternative cholesterol-lowering agent to reduce cardiovascular event rates 1
- Also consider PCSK9 inhibitor monoclonal antibody therapy or inclisiran siRNA for statin-intolerant patients 1
Management of Elevated Triglycerides
Triglycerides ≥150 mg/dL (≥1.7 mmol/L) and/or Low HDL-C
- Intensify lifestyle therapy and optimize glycemic control first 1
- HDL-C thresholds: <40 mg/dL (<1.0 mmol/L) for men, <50 mg/dL (<1.3 mmol/L) for women 1
Icosapent Ethyl (High-Dose Omega-3)
- Consider icosapent ethyl (purified eicosapentaenoic acid ethyl ester) for patients with persistently elevated triglycerides despite statin therapy to reduce residual cardiovascular risk 7, 8
- Particularly beneficial in patients with diabetes and established ASCVD 8
Fibrates
- Reserve fibrates (fenofibrate or gemfibrozil) for severe hypertriglyceridemia (typically >500 mg/dL) to prevent acute pancreatitis 7
- Critical pitfall: Combination of fibrates with statins increases risk of myositis; monitor closely for unexplained muscle pain, tenderness, or weakness 4
- Gemfibrozil has higher drug interaction risk with statins than fenofibrate 7
Monitoring Strategy
- Reassess lipid panel 4-12 weeks after initiating or changing statin/lipid-lowering therapy to confirm adequate response and assess adherence 1, 2
- Annual lipid monitoring once stable on therapy 1, 2
- Monitor for statin-associated muscle symptoms (myalgia, weakness) and check creatine kinase if symptoms develop 4
- Baseline and periodic monitoring of liver transaminases (ALT/AST) when using high-dose statins 4
Special Populations and Considerations
Age >75 Years
- Continue statin therapy if already established and well-tolerated 1
- For new initiation, consider moderate-intensity statin after shared decision-making discussion of benefits and risks 1
Chronic Kidney Disease
- Statin therapy remains beneficial; dose adjustments may be needed for advanced CKD (eGFR <60 mL/min/1.73 m²) 4
- Atorvastatin does not require dose adjustment until more advanced kidney disease 4
Pregnancy
- Statin therapy is contraindicated in pregnancy 1
Common Pitfalls to Avoid
- Do not delay statin initiation in patients with LDL-C ≥190 mg/dL to trial lifestyle modifications first; start high-intensity statin immediately 3, 4
- Do not use baseline LDL-C alone to determine statin intensity in diabetes patients aged 40-75 years; use presence of additional ASCVD risk factors instead 1
- Do not discontinue statins due to intolerance without attempting alternative statins, lower doses, or intermittent dosing schedules 1, 4
- Do not combine gemfibrozil with statins due to high myopathy risk; fenofibrate is safer if fibrate needed 7
- Do not add PCSK9 inhibitors before maximizing statin therapy and adding ezetimibe in most cases, due to cost considerations 2, 4