What is the management plan for a patient with hypercholesterolemia (elevated total cholesterol) of 220?

Management of Total Cholesterol 220 mg/dL

Begin high-intensity statin therapy immediately (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) combined with therapeutic lifestyle changes to reduce LDL-C by at least 30-50% and achieve an LDL-C goal of <100 mg/dL. 1

Initial Risk Stratification Required

Before finalizing treatment intensity, you must determine the patient's cardiovascular risk category:

• Check for established ASCVD (history of MI, ACS, stroke, TIA, PAD, prior revascularization) - if present, patient is automatically high-risk with LDL-C goal <100 mg/dL 2
• Screen for diabetes mellitus (check HbA1c, fasting glucose) - diabetes qualifies as CHD risk equivalent with LDL-C goal <100 mg/dL 2
• Assess for familial hypercholesterolemia - obtain family history of premature CVD (men <55 years, women <65 years) and personal history of elevated cholesterol since childhood 1
• Calculate 10-year ASCVD risk using Framingham risk scoring if no established disease - includes age, sex, total cholesterol, HDL-C, blood pressure, smoking status, diabetes 2

Pharmacological Management

High-Intensity Statin Therapy (First-Line)

Start immediately without waiting for lifestyle modification trial if total cholesterol is 220 mg/dL:

• Atorvastatin 40-80 mg daily OR rosuvastatin 20-40 mg daily to achieve 30-50% LDL-C reduction 1
• For patients with established ASCVD or diabetes, statins reduce major vascular events by 22% and strokes by 25% 2
• The clinical benefit depends on the extent of LDL-C lowering, not the specific statin type 2

When to Add Ezetimibe

Add ezetimibe 10 mg daily if after 4-6 weeks on maximally tolerated statin: 1, 3

• LDL-C reduction is <50% from baseline, OR
• LDL-C remains ≥100 mg/dL in high-risk patients, OR
• LDL-C remains ≥130 mg/dL in moderate-risk patients

Ezetimibe is FDA-approved as adjunct to statin when additional LDL-C lowering is needed 3

Consider PCSK9 Inhibitors

May consider PCSK9 inhibitor (alirocumab or evolocumab) if: 2

• Baseline LDL-C ≥220 mg/dL AND on-treatment LDL-C ≥130 mg/dL despite maximally tolerated statin plus ezetimibe (Class IIb recommendation)
• Heterozygous familial hypercholesterolemia with LDL-C ≥100 mg/dL on maximal therapy

Therapeutic Lifestyle Changes (Concurrent, Not Sequential)

Initiate simultaneously with statin therapy, not as a trial period before medication: 1

• Reduce saturated fat to <7% of total calories and dietary cholesterol to <200 mg/day 1
• Add plant stanols/sterols 2 g/day (available in fortified spreads/margarines) 1
• Increase soluble fiber to 10-25 g/day (oats, beans, psyllium) - can lower LDL-C by 0.2-0.35 mmol/L 1
• Reduce trans fat to <1% of caloric intake 1
• Exercise 30-60 minutes of moderate intensity most days (preferably daily) 1
• Target 10% weight reduction in first year if BMI ≥25 kg/m² 1

Target LDL-C Goals Based on Risk Category

• Very high-risk ASCVD (multiple major events or 1 major event + multiple high-risk conditions): LDL-C <70 mg/dL 2
• High-risk (established ASCVD, diabetes, 10-year risk >20%): LDL-C <100 mg/dL 2
• Moderate risk (2+ risk factors, 10-year risk 10-20%): LDL-C <130 mg/dL 2
• Lower risk (0-1 risk factors, 10-year risk <10%): LDL-C <160 mg/dL 2

Monitoring Protocol

• Reassess lipid panel at 4-6 weeks after initiating statin therapy 1
• Recheck at 2 months after any medication dose adjustment 1
• Perform liver enzyme testing (ALT, AST) at baseline and as clinically indicated - discontinue if ALT/AST ≥3× ULN persists 3
• Screen for secondary causes if LDL remains elevated: check TSH, liver function, renal function, fasting glucose/HbA1c 1

Management of Additional Lipid Abnormalities

If triglycerides >200 mg/dL or HDL-C <40 mg/dL after achieving LDL-C goal: 1

• Target non-HDL-C <130 mg/dL (calculated as total cholesterol minus HDL-C) 2, 1
• Consider adding fenofibrate or niacin (gemfibrozil not recommended with statins due to increased myopathy risk) 2

Critical Safety Monitoring

Discontinue statin and ezetimibe immediately if: 3

• Unexplained muscle pain, tenderness, or weakness develops (check CK level)
• Signs of rhabdomyolysis appear (dark urine, severe muscle pain, acute kidney injury)
• Most rhabdomyolysis cases in post-marketing reports occurred with concomitant fibrates or other myopathy-associated drugs 3

Common Pitfalls to Avoid

• Do not delay statin therapy to attempt lifestyle modification alone when total cholesterol is 220 mg/dL - guidelines recommend simultaneous initiation 1
• Do not use fibrates as monotherapy for hypercholesterolemia - statins are first-line 2
• Do not combine gemfibrozil with statins - use fenofibrate if fibrate needed due to lower myopathy risk 3
• Do not administer ezetimibe simultaneously with bile acid sequestrants - give ezetimibe ≥2 hours before or ≥4 hours after 3

Expected Outcomes

• High-intensity statin should achieve 30-40% LDL-C reduction within 6 weeks 1
• Combined statin plus lifestyle changes should reduce total cholesterol from 220 mg/dL to <175 mg/dL and LDL-C to <100 mg/dL in most patients 2, 1
• Statin therapy in high-risk patients reduces stroke risk by 25% over 5 years 2