Dyslipidemia Management Flow Chart

Step 1: Risk Stratification and Initial Assessment

Assess cardiovascular disease (CVD) risk category to determine treatment intensity—this is the foundation of all management decisions. 1

Risk Categories:

Very High Risk: Clinical atherosclerotic CVD (prior MI, ACS, stroke, coronary revascularization, peripheral vascular disease, AAA) 1
High Risk: CVD risk equivalents including diabetes mellitus, chronic kidney disease, or calculated 10-year CVD risk ≥12% (SCORE ≥10%) 2, 1
Moderate Risk: 10-year CVD risk 6-12% (SCORE ≥5% and <10%) 2, 1
Low Risk: 10-year CVD risk <6% (SCORE <1%) 2, 1

Initial Lipid Testing:

Obtain at least two lipid measurements 1-12 weeks apart before starting drug therapy to establish baseline (exception: ACS or very high-risk patients where immediate treatment is warranted) 2, 3
Measure: Total cholesterol, LDL-C, HDL-C, triglycerides 2
Check baseline ALT and CK before initiating therapy 2, 3

Step 2: Lifestyle Modifications (All Patients)

Initiate Mediterranean-style diet and aerobic exercise as first-line therapy for all risk categories. 1

Dietary Intervention:

Mediterranean-style diet: Emphasize vegetables, fruits, whole grains, legumes, nuts, and olive oil as primary fat source 1
Total fat <30% of calories, saturated fat 8-10% of total calories 4
High-fiber diet 4

Physical Activity:

At least 150 minutes per week of moderate-intensity exercise OR 75 minutes per week of vigorous-intensity exercise 1

Address Secondary Causes:

Screen for and treat hypothyroidism, diabetes mellitus, obesity 2, 4
Discontinue contributory medications (estrogen therapy, thiazide diuretics, beta-blockers if causing massive TG elevation) 5

Step 3: Pharmacologic Treatment Based on Risk Category

For Very High Risk (Clinical ASCVD):

Initiate high-intensity statin therapy immediately without targeting specific LDL-C goals. 1

High-intensity statins: Atorvastatin 40-80 mg daily OR rosuvastatin 20-40 mg daily 1
If very high risk, add ezetimibe 10 mg daily to high-intensity statin 1, 6
For patients with ACS, start statin therapy irrespective of LDL-C levels 2

For High Risk (CVD Risk Equivalents):

Initiate moderate-to-high intensity statin therapy. 1

Moderate-intensity statins: Atorvastatin 10-20 mg, simvastatin 20-40 mg, pravastatin 40-80 mg, or lovastatin 40 mg daily 1
High-intensity statins if multiple risk factors present 1

For Moderate Risk:

Consider moderate-intensity statin therapy based on clinical judgment and patient discussion 2
Emphasize lifestyle modifications first 2

For Low Risk:

Focus on lifestyle modifications 2
Pharmacotherapy generally not indicated unless familial dyslipidemia present 2

For Severe Hypertriglyceridemia (TG >2000 mg/dL):

Fenofibrate 54-160 mg daily (individualize dose) to reduce pancreatitis risk 5
Optimize glycemic control in diabetic patients first 5
Avoid gemfibrozil with statins due to severe myopathy risk 3, 7

Step 4: Monitoring Protocol

Lipid Monitoring:

Recheck lipids 8 (±4) weeks after initiating or adjusting therapy 2, 3
Continue rechecking 8 (±4) weeks after each dose adjustment until stable 2, 3
Once stable, monitor annually (unless adherence issues) 2, 3

Liver Enzyme Monitoring:

Check ALT 8-12 weeks after starting therapy or dose increase 2, 3
No routine ALT monitoring thereafter 2, 3
If ALT <3x ULN: Continue therapy, recheck in 4-6 weeks 2, 3
If ALT ≥3x ULN: Discontinue or reduce dose, investigate other causes 2, 3

CK Monitoring:

No routine CK monitoring in asymptomatic patients 3
Check CK immediately if muscle symptoms develop (pain, tenderness, weakness) 3, 7

Step 5: Management of Statin-Associated Muscle Symptoms

If Muscle Symptoms Develop:

Check CK level immediately and manage based on severity. 2, 3, 7

CK <4x ULN with symptoms:

2-4 weeks statin washout 2
If symptoms persist: Consider non-statin causes 2
If symptoms improve: Try second statin at usual or starting dose 2
If symptoms recur: Use low-dose potent statin (atorvastatin or rosuvastatin) with alternate-day or once/twice weekly dosing 2

CK 4-10x ULN without symptoms:

Continue statin with more frequent CK monitoring 2, 3, 7

CK 4-10x ULN with symptoms:

Stop statin, monitor CK normalization 2, 3, 7
Re-challenge at lower dose after normalization 2

CK >10x ULN:

Immediately discontinue statin 2, 3, 7
Check renal function 2, 3
Monitor CK every 2 weeks until normalization 2, 3
6 weeks washout before considering re-challenge 2

Step 6: Escalation Strategy for Inadequate Response

If LDL-C remains elevated despite maximally tolerated statin dose, add non-statin therapy sequentially. 2

Sequential Add-On Therapy:

Add ezetimibe 10 mg daily 2, 6
If still inadequate, add bile acid sequestrant (administer ≥2 hours before or ≥4 hours after ezetimibe) 2, 6
If still inadequate, add fenofibrate (not gemfibrozil) 2, 5
Consider PCSK9 inhibitors for very high-risk patients not at goal 2

Combination Therapy Considerations:

Ezetimibe + statin: Safe and effective combination 6
Fenofibrate + statin: Acceptable combination (avoid gemfibrozil) 5, 6
Ezetimibe + fenofibrate: Indicated for mixed hyperlipidemia 6

Step 7: Special Populations

Renal Impairment:

Mild-moderate renal impairment: Start fenofibrate at 54 mg daily, titrate based on response and renal function 5
Severe renal impairment: Avoid fenofibrate 5

Elderly Patients:

Dose selection based on renal function 5
Higher risk for myopathy: Monitor closely for muscle symptoms 3, 7

High-Risk Patients for Myopathy:

Monitor vigilantly in: elderly (especially >80 years, women), small body frame/frailty, renal impairment, polypharmacy, uncontrolled hypothyroidism 3, 7

Critical Pitfalls to Avoid

Do NOT target specific LDL-C goals—focus on appropriate statin dose intensity for risk category 2, 1
Do NOT perform routine ALT monitoring beyond initial 8-12 week check 2, 3
Do NOT perform routine CK monitoring in asymptomatic patients 3
Do NOT combine statins with gemfibrozil—use fenofibrate if fibrate needed 3, 7, 5
Do NOT restart statins at same dose after myopathy episode—use lower dose or different agent 3, 7
Do NOT attribute all muscle pain to statins—rule out exercise, strenuous work, other medical conditions 3, 7
Do NOT continue therapy if CK >10x ULN—stop immediately and check renal function 2, 3, 7

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