What initial lipid‑lowering medication should be started in an adult with total cholesterol 209 mg/dL and LDL‑C 145 mg/dL?

Initiate Moderate‑Intensity Statin Therapy Immediately

For an adult with total cholesterol 209 mg/dL and LDL‑C 145 mg/dL, start a moderate‑intensity statin (atorvastatin 10–20 mg or rosuvastatin 5–10 mg daily) after calculating the 10‑year ASCVD risk and assessing for additional cardiovascular risk factors. 1

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Risk Stratification Determines Treatment Intensity

Calculate 10‑Year ASCVD Risk First

• Use the Pooled Cohort Equations to estimate 10‑year risk of atherosclerotic cardiovascular disease (first‑occurrence nonfatal/fatal MI and nonfatal/fatal stroke). 1
• The risk calculator is available at http://my.americanheart.org/cvriskcalculator and http://www.cardiosource.org/en/Science-And-Quality/Practice-Guidelines-and-Quality-Standards/2013-Prevention-Guideline-Tools.aspx. 1

Treatment Algorithm by Risk Category

10‑Year ASCVD Risk ≥ 10 %

• Initiate moderate‑ to high‑intensity statin therapy immediately. 1
• Recommended regimens: atorvastatin 10–20 mg daily or rosuvastatin 5–10 mg daily. 1
• Target at least a 30–50 % reduction in LDL‑C from baseline (145 mg/dL → goal < 100 mg/dL, ideally < 70 mg/dL if very high risk). 1
• Do not delay statin initiation while pursuing lifestyle changes alone; both should start concurrently. 1

10‑Year ASCVD Risk 7.5 % to < 10 %

• Selectively offer a statin after a clinician‑patient discussion of potential benefits, adverse effects, drug interactions, and patient preferences. 1
• The likelihood of benefit is smaller in this group than in those with ≥ 10 % risk, but persistently elevated LDL‑C ≥ 160 mg/dL or other risk‑enhancing factors (family history of premature ASCVD, high‑sensitivity CRP ≥ 2 mg/L, coronary artery calcium score ≥ 300 Agatston units or ≥ 75th percentile, ankle‑brachial index < 0.9) favor statin initiation. 1

10‑Year ASCVD Risk < 7.5 %

• Prioritize intensive lifestyle modification for at least 3 months before considering pharmacotherapy. 1
• Re‑measure fasting lipid panel 6–12 weeks after lifestyle implementation. 1
• Consider a moderate‑intensity statin only after shared decision‑making if risk‑enhancing factors are present. 1

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Special Populations Requiring Immediate Statin Therapy

LDL‑C ≥ 190 mg/dL (Severe Primary Hypercholesterolemia)

• Start high‑intensity statin therapy immediately (atorvastatin 40–80 mg or rosuvastatin 20–40 mg daily) at age ≥ 21 years, regardless of 10‑year ASCVD risk. 1
• These individuals have a high lifetime risk for ASCVD events due to prolonged exposure to markedly elevated LDL‑C from genetic causes. 1
• Each 39 mg/dL reduction in LDL‑C by statin therapy reduces ASCVD risk by approximately 20 %. 1

Diabetes Mellitus (Age 40–75 Years)

• Initiate moderate‑ to high‑intensity statin therapy regardless of baseline LDL‑C, as diabetes itself is a high‑risk condition. 1
• Target LDL‑C < 100 mg/dL (or < 70 mg/dL for very high‑risk patients with established ASCVD or multiple risk factors). 1

Established ASCVD (Secondary Prevention)

• Start high‑intensity statin therapy immediately (atorvastatin 40–80 mg or rosuvastatin 20–40 mg daily) while the patient is in the hospital if presenting with an acute coronary syndrome. 1
• Target at least a 50 % reduction in LDL‑C from baseline. 1
• Blood lipids should be checked 4–6 weeks after the acute event to determine whether the target has been reached. 1

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Statin Intensity Definitions and Expected LDL‑C Reductions

Intensity	LDL‑C Lowering	Statins and Doses
High	≥ 50 %	Atorvastatin 40–80 mg, Rosuvastatin 20–40 mg [1]
Moderate	30–49 %	Atorvastatin 10–20 mg, Rosuvastatin 5–10 mg, Simvastatin 20–40 mg, Pravastatin 40–80 mg [1]
Low	< 30 %	Simvastatin 10 mg, Pravastatin 10–20 mg, Lovastatin 20 mg, Fluvastatin 20–40 mg [1]

• Boldface doses indicate specific statins and doses evaluated in randomized controlled trials that demonstrated a reduction in major cardiovascular events. 1
• Individual responses to statin therapy vary; the percent reductions are estimates from large populations. 1

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Lifestyle Modifications (Foundational for All Patients)

Dietary Pattern

• Consume a diet emphasizing vegetables, fruits, whole grains, legumes, healthy protein sources (low‑fat dairy, skinless poultry, fish/seafood, nuts), and nontropical vegetable oils. 1
• Limit saturated fat to < 7 % of total energy and replace with monounsaturated or polyunsaturated fats. 1
• Restrict dietary cholesterol to < 200 mg/day. 1
• Eliminate trans fats completely. 1
• Limit added sugars to < 6 % of total daily calories (≈ 30 g on a 2,000‑kcal diet). 1
• Avoid sugar‑sweetened beverages and limit red meat intake. 1

Weight Management

• Adjust caloric intake to avoid weight gain; in overweight/obese patients, promote weight loss. 1
• A 5–10 % reduction in body weight can improve lipid parameters and reduce cardiovascular risk. 1

Physical Activity

• Engage in ≥ 150 minutes/week of moderate‑intensity aerobic activity (or ≥ 75 minutes/week vigorous), lasting on average 40 minutes per session. 1
• Regular aerobic exercise reduces triglycerides by approximately 11 % and improves overall cardiovascular health. 1

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Monitoring and Follow‑Up Strategy

Lipid Panel Reassessment

• Re‑check fasting lipid panel 4–8 weeks after initiating or adjusting statin therapy to assess LDL‑C reduction. 1
• If LDL‑C target is not achieved, consider increasing statin intensity or adding ezetimibe 10 mg daily (provides an additional 13–20 % LDL‑C reduction). 1

Liver Enzyme Monitoring

• Consider testing liver enzymes (ALT, AST) before initiating therapy and as clinically indicated thereafter. 1
• If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue the statin. 1

Muscle Symptom Surveillance

• Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. 1
• Risk factors for myopathy include age ≥ 65 years, uncontrolled hypothyroidism, renal impairment, concomitant use of certain drugs (e.g., fibrates, cyclosporine, macrolides, azole antifungals), and higher statin doses. 1
• If markedly elevated creatine kinase (CK) levels occur or myopathy is diagnosed or suspected, discontinue the statin. 1

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Special Dosing Considerations

Asian Patients

• Initiate rosuvastatin at 5 mg once daily due to higher systemic exposure in Asian populations. 2
• Consider risks and benefits if not adequately controlled at doses up to 20 mg once daily. 2

Severe Renal Impairment (Not on Hemodialysis)

• Initiate rosuvastatin at 5 mg once daily; do not exceed 10 mg once daily. 2

Elderly Patients (> 75 Years)

• In individuals with clinical ASCVD who are > 75 years of age, it is reasonable to continue statin therapy if tolerating it, according to the potential for ASCVD risk‑reduction benefits, adverse effects, and patient preferences. 1
• The use of statin therapy should be individualized in this age group, as older trial participants were likely healthier than many older individuals in the general population. 1

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Common Pitfalls to Avoid

Do Not Delay Statin Initiation in High‑Risk Patients

• For individuals with 10‑year ASCVD risk ≥ 7.5 %, diabetes (age 40–75 years), established ASCVD, or LDL‑C ≥ 190 mg/dL, do not postpone statin therapy while attempting lifestyle changes alone; both should start concurrently. 1

Do Not Overlook Secondary Causes of Hyperlipidemia

• Before attributing hypercholesterolemia to primary dyslipidemia, evaluate for secondary causes such as hypothyroidism, uncontrolled diabetes, nephrotic syndrome, chronic kidney disease, biliary obstruction, certain medications (e.g., diuretics, cyclosporine, glucocorticoids, oral estrogens, protease inhibitors), and excessive alcohol intake. 1
• Treating these conditions can markedly improve lipid levels and may reduce the need for pharmacotherapy. 1

Do Not Use LDL‑C Targets to Guide Initial Statin Selection

• The 2013 ACC/AHA guideline emphasizes using statin intensity (high, moderate, low) rather than treating to specific LDL‑C targets, as this approach is supported by randomized controlled trial evidence. 1
• However, the 2018 ACC/AHA guideline reintroduces LDL‑C thresholds for adding non‑statin therapy (e.g., ezetimibe, PCSK9 inhibitors) in certain high‑risk groups. 1

Do Not Ignore Risk‑Enhancing Factors

• In patients with borderline or intermediate risk (10‑year ASCVD risk 5 % to < 7.5 %), consider risk‑enhancing factors such as family history of premature ASCVD, primary LDL‑C ≥ 160 mg/dL, high‑sensitivity CRP ≥ 2 mg/L, coronary artery calcium score ≥ 300 Agatston units or ≥ 75th percentile, or ankle‑brachial index < 0.9 to inform treatment decisions. 1

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Summary of Treatment Algorithm

1. Calculate 10‑year ASCVD risk using the Pooled Cohort Equations. 1
2. Assess for special populations (LDL‑C ≥ 190 mg/dL, diabetes age 40–75 years, established ASCVD) that require immediate statin therapy regardless of risk score. 1
3. Initiate moderate‑ to high‑intensity statin (atorvastatin 10–20 mg or rosuvastatin 5–10 mg) if 10‑year ASCVD risk ≥ 7.5 % or if risk‑enhancing factors are present. 1
4. Start intensive lifestyle modifications concurrently with statin therapy (diet, weight loss, physical activity). 1
5. Re‑check fasting lipid panel 4–8 weeks after statin initiation to assess LDL‑C reduction. 1
6. Adjust statin intensity or add ezetimibe if LDL‑C target (< 100 mg/dL, or < 70 mg/dL for very high risk) is not achieved. 1
7. Monitor for adverse effects (muscle symptoms, liver enzyme elevations) and adjust therapy as needed. 1

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This evidence‑based approach prioritizes proven cardiovascular mortality benefit from statin therapy while tailoring treatment intensity to individual risk, ensuring the best possible outcomes for patients with hypercholesterolemia. 1