How to manage dyslipidemia?

Management of Dyslipidemia

Start all patients with high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) targeting LDL-C <100 mg/dL for primary prevention and <70 mg/dL for established cardiovascular disease, adding ezetimibe 10 mg if targets are not met at 8 weeks. 1, 2

Initial Assessment and Risk Stratification

• Obtain at least two fasting lipid measurements 1-12 weeks apart before initiating therapy, except in acute coronary syndrome or very high-risk patients where immediate treatment is warranted 3, 1, 2
• Use the SCORE system to estimate 10-year risk of fatal atherosclerotic events in asymptomatic adults >40 years without established CVD, diabetes, CKD, or familial hypercholesterolemia 3, 2
• Test lipids annually in all adults, or every 2 years if low-risk values are present (LDL <100 mg/dL, HDL >50 mg/dL, triglycerides <150 mg/dL) 3, 4

Treatment Targets by Risk Category

Very High-Risk Patients (established CVD, diabetes with target organ damage, or familial hypercholesterolemia):

• LDL-C goal <70 mg/dL (1.8 mmol/L), or ≥50% reduction if baseline is 70-135 mg/dL 1, 2
• Non-HDL-C <100 mg/dL and apoB <80 mg/dL as secondary targets 2

High-Risk Patients (diabetes without complications, moderate CKD, or 10-year SCORE risk 5-10%):

• LDL-C goal <100 mg/dL (2.6 mmol/L), or ≥50% reduction if baseline is 100-200 mg/dL 2

Diabetes-Specific Targets:

• Initiate statin therapy regardless of baseline LDL levels for all patients ≥40 years 1, 4
• Target LDL <100 mg/dL, HDL >40 mg/dL (>50 mg/dL for women), triglycerides <150 mg/dL 3, 4

Lifestyle Modifications (Mandatory First Step)

Dietary Interventions:

• Reduce saturated fat to <7% of total daily calories 1, 4
• Limit dietary cholesterol to <200 mg/day 1
• Eliminate trans fats to <1% of total calories 1
• Increase soluble fiber intake to 10-25 g/day 1
• Add plant stanols/sterols 2 g/day for additional LDL lowering 1
• For elevated triglycerides specifically: reduce carbohydrates (especially high glycemic index foods) and replace with mono- and polyunsaturated fatty acids 5, 6

Weight and Exercise:

• Target 5-10% body weight reduction, which produces a 20% decrease in triglycerides 1
• Engage in ≥150 minutes/week of moderate-intensity aerobic exercise, which reduces triglycerides by approximately 11% 1
• Each 10% reduction in body weight is associated with a 7.6% reduction in LDL-C 7

Additional Measures:

• Smoking cessation 3, 4
• Moderate alcohol consumption (restrict completely if triglycerides elevated) 4, 6

Pharmacological Treatment Algorithm

Step 1: Initiate High-Intensity Statin Therapy

Choice of Statin:

• Use high-intensity statins (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) when ≥50% LDL-C reduction is needed 1, 2
• Higher doses may also moderately reduce triglycerides 3, 4
• For diabetes patients with type 1 in good glycemic control who are overweight/obese, treat as type 2 diabetes 3

Step 2: Add Ezetimibe if Target Not Met

• Add ezetimibe 10 mg daily for an additional 13-20% LDL-C reduction if targets are not met with maximally tolerated statin 1, 2
• Administer ezetimibe either ≥2 hours before or ≥4 hours after bile acid sequestrants 8
• Ezetimibe is FDA-approved in combination with statins for primary hyperlipidemia, heterozygous and homozygous familial hypercholesterolemia 8

Step 3: Consider Additional Agents for Refractory Cases

For Persistent LDL-C Elevation:

• Consider PCSK9 monoclonal antibody therapy for very high-risk patients not reaching goals with statin plus ezetimibe 2
• Bile acid sequestrants as alternative add-on therapy 3, 2

For Elevated Triglycerides (Primary or Combined with High LDL):

• Fibric acid derivatives (gemfibrozil or fenofibrate) for triglycerides >150 mg/dL 3, 4
• Nicotinic acid (niacin) as alternative or combination therapy 3, 4
• Critical caveat: Do NOT combine gemfibrozil with statins due to increased myopathy risk; fenofibrate is safer for combination therapy 3
• Ezetimibe can be combined with fenofibrate for mixed hyperlipidemia 8

For Severe Hypertriglyceridemia (≥500 mg/dL):

• Immediate pharmacological treatment to minimize pancreatitis risk 4, 6
• Severe dietary fat restriction (<10% of calories) 4
• Fibrates are first-line therapy 4
• Improved glycemic control is particularly effective in diabetic patients 4

For Low HDL-C:

• Lifestyle interventions (weight loss, increased physical activity, smoking cessation) are primary 4
• Nicotinic acid or fibrates if pharmacological intervention needed 3, 4

Monitoring Protocol

Lipid Panel Monitoring:

• Check fasting lipid panel at 8 (±4) weeks after initiating or adjusting therapy 3, 1, 2
• Recheck at 8 (±4) weeks after each dose adjustment until target is reached 3, 1, 2
• Once goals achieved, follow-up every 6-12 months (annually unless adherence problems exist) 3, 4, 2

Liver Enzyme Monitoring:

• Measure ALT before treatment and once at 8-12 weeks after starting therapy or dose increase 3, 1, 2
• Routine control of ALT thereafter is NOT recommended during lipid-lowering treatment 3, 2
• If ALT <3x ULN: continue therapy and recheck in 4-6 weeks 3, 2
• If ALT ≥3x ULN persists: consider withdrawal of therapy 1, 2

Creatine Kinase (CK) Monitoring:

• Measure CK before starting therapy 3, 1, 2
• If baseline CK >4x ULN: do not start drug therapy; recheck 3, 2
• Be alert for myopathy in high-risk patients: elderly, concomitant interfering therapy, multiple medications, liver/renal disease, or athletes 3, 2

Management of CK Elevation:

• If CK >10x ULN: stop treatment immediately, check renal function, monitor CK every 2 weeks 3, 2
• If CK <10x ULN without symptoms: continue therapy while monitoring CK 3, 2
• If CK <10x ULN with symptoms: stop statin, monitor normalization, then re-challenge with lower dose 3, 2
• If CK <4x ULN: continue treatment and monitor 3

Management of Statin-Associated Muscle Symptoms

For Symptomatic Patients with CK <4x ULN:

• 2-4 weeks washout of statin 3, 2
• If symptoms persist: statin re-challenge 3
• If symptoms improve: try second statin at usual or starting dose 3, 2
• If symptoms recur: try low-dose third potent statin or alternate-day/once-twice weekly dosing 3, 2

For CK ≥4x ULN +/- Rhabdomyolysis:

• 6 weeks washout until normalization of CK, creatinine, and symptoms 3, 2
• Follow same re-challenge algorithm as above 3, 2

Goal: Achieve LDL-C target with maximally tolerated statin dose, then add ezetimibe, bile acid absorption inhibitor, or fibrate (not gemfibrozil) as needed 3, 2

Special Populations

Type 1 Diabetes:

• Patients in good glycemic control typically have normal lipid levels unless overweight/obese 3
• If overweight/obese, treat with same approach as type 2 diabetes 3

Familial Hypercholesterolemia:

• Heterozygous FH: intense-dose statin therapy, often in combination with ezetimibe 2
• Homozygous FH: combination of statin, ezetimibe, and other LDL-C lowering therapies; consider PCSK9 inhibitors 2, 8
• Test children with FH from age 5 years, or earlier if homozygous FH suspected 2

Acute Coronary Syndrome:

• Initiate or continue high-dose statins early after admission regardless of initial LDL-C levels 2

Common Pitfalls and How to Avoid Them

• Inadequate glycemic control in diabetic patients with hypertriglyceridemia: Always optimize glucose control first, as this is particularly effective for reducing triglycerides 4
• Combining gemfibrozil with statins: Use fenofibrate instead to avoid severe myopathy risk 3
• Insufficient monitoring for adverse effects with combination therapy: Follow the structured monitoring protocol above 4
• Neglecting lifestyle modifications: These remain the foundation even with pharmacotherapy and should be reinforced at every visit 3, 1, 4
• Administering ezetimibe with bile acid sequestrants: Separate by ≥2 hours before or ≥4 hours after 8
• Over-monitoring liver enzymes: Routine ALT monitoring after initial 8-12 week check is not recommended and wastes resources 3, 2