ASCVD Risk Evaluation and Preventive Therapy

Calculate 10-Year ASCVD Risk Using the Pooled Cohort Equations

For adults aged 40–75 years without clinical ASCVD or diabetes and with LDL-C 70–189 mg/dL, use the Pooled Cohort Equations to estimate 10-year ASCVD risk as the foundation for all treatment decisions. 1 This risk calculator predicts first-occurrence nonfatal and fatal MI and nonfatal and fatal stroke, and is validated for non-Hispanic White and African-American adults. 1

Four Mandatory Statin Benefit Groups (Treat Regardless of Risk Score)

1. Clinical ASCVD (Secondary Prevention)

Adults ≤75 years with established ASCVD (prior MI, stroke, TIA, PAD, or revascularization) require high-intensity statin therapy immediately (atorvastatin 40–80 mg or rosuvastatin 20–40 mg daily), targeting ≥50% LDL-C reduction. 1
If high-intensity statin is contraindicated or not tolerated, use moderate-intensity statin as second-line therapy. 1
Adults >75 years with ASCVD: Continue statin if already established; for new initiation, moderate-to-high intensity statin is reasonable after shared decision-making discussion weighing ASCVD benefit versus adverse effects and drug interactions. 1

2. Primary LDL-C ≥190 mg/dL

Adults ≥21 years with LDL-C ≥190 mg/dL require high-intensity statin therapy immediately without calculating 10-year risk. 1
First, evaluate for secondary causes of hyperlipidemia (hypothyroidism, nephrotic syndrome, obstructive liver disease). 1
Target ≥50% LDL-C reduction from baseline; if maximal statin fails to achieve this, add ezetimibe or consider PCSK9 inhibitor. 1

3. Diabetes (Ages 40–75 Years, LDL-C 70–189 mg/dL)

All adults aged 40–75 years with diabetes require at least moderate-intensity statin therapy regardless of calculated 10-year ASCVD risk (atorvastatin 10–20 mg, rosuvastatin 5–10 mg, simvastatin 20–40 mg, or pravastatin 40–80 mg daily). 1, 2
Upgrade to high-intensity statin if estimated 10-year ASCVD risk ≥7.5% or multiple additional risk factors are present. 1
For diabetic patients <40 years or >75 years: Assess ASCVD benefit versus adverse effects, drug interactions, and patient preferences before initiating or intensifying therapy; continuation is reasonable if already established. 1, 2

4. Primary Prevention Without Diabetes (10-Year ASCVD Risk ≥7.5%)

Adults aged 40–75 years with LDL-C 70–189 mg/dL and estimated 10-year ASCVD risk ≥7.5% require moderate-to-high intensity statin therapy. 1

Risk-Stratified Approach for Primary Prevention (No Diabetes, LDL-C 70–189 mg/dL)

10-Year ASCVD Risk	Recommendation	Statin Intensity	Strength
≥20% (High)	Initiate statin immediately	High-intensity (atorvastatin 40–80 mg or rosuvastatin 20–40 mg)	Class I [1]
≥7.5% to <20% (Intermediate)	Initiate statin after risk discussion	Moderate-to-high intensity; target ≥30% LDL-C reduction	Class I [1]
5% to <7.5% (Borderline)	Offer moderate-intensity statin after shared decision-making; consider risk-enhancing factors	Moderate-intensity (atorvastatin 10–20 mg, rosuvastatin 5–10 mg)	Class IIa [1]
<5% (Low)	Consider risk-enhancing factors and patient preferences; shared decision-making essential	Moderate-intensity if risk enhancers present	Class IIb [1]

Risk-Enhancing Factors to Guide Borderline and Intermediate Risk Decisions

When 10-year ASCVD risk is 5% to <20% and treatment decision remains uncertain, consider these factors to reclassify risk upward: 1

Family history of premature ASCVD (first-degree male relative <55 years or female relative <65 years) 1
Persistently elevated LDL-C ≥160 mg/dL or other genetic hyperlipidemia 1
Chronic kidney disease (eGFR <60 mL/min/1.73 m²) 1
Metabolic syndrome 1
Chronic inflammatory conditions (rheumatoid arthritis, lupus, HIV infection) 1
High-sensitivity C-reactive protein ≥2 mg/L 1
Conditions specific to women: preeclampsia, premature menopause (<40 years), or preterm delivery 1
South Asian ancestry 1
Ankle-brachial index <0.9 1

Coronary Artery Calcium (CAC) Scoring for Uncertain Risk Decisions

For intermediate-risk (≥7.5% to <20%) or selected borderline-risk (5% to <7.5%) adults when treatment decision remains uncertain after considering risk-enhancing factors, CAC scoring is reasonable to guide the clinician-patient discussion. 1

CAC Score Interpretation:

CAC = 0: Reasonable to withhold statin therapy and reassess in 5–10 years, unless diabetes, family history of premature CHD, or current smoking is present. 1
CAC 1–99: Reasonable to initiate statin therapy for patients ≥55 years. 1
CAC ≥100 or ≥75th percentile for age/sex/ethnicity: Initiate statin therapy and reclassify to higher risk category. 1

Statin Intensity Definitions and Target LDL-C Reduction

High-Intensity Statin (≥50% LDL-C Reduction):

Atorvastatin 40–80 mg daily 1
Rosuvastatin 20–40 mg daily 1

Moderate-Intensity Statin (30–50% LDL-C Reduction):

Atorvastatin 10–20 mg daily 1
Rosuvastatin 5–10 mg daily 1
Simvastatin 20–40 mg daily 1
Pravastatin 40–80 mg daily 1

Target LDL-C reduction: ≥30% for intermediate risk (≥7.5% to <20%); ≥50% for high risk (≥20%) or established ASCVD. 1

Additional Lipid-Lowering Agents Beyond Statins

When to Add Non-Statin Therapy:

For patients with clinical ASCVD on maximally tolerated statin therapy with LDL-C still ≥70 mg/dL, add ezetimibe 10 mg daily as first-line non-statin therapy. 1, 3

For "very high risk" ASCVD patients (≥2 major ASCVD events OR 1 major event plus ≥2 high-risk conditions such as diabetes, prior bypass/PCI, or multiple major risk factors) on maximally tolerated statin plus ezetimibe with LDL-C still ≥70 mg/dL, consider adding a PCSK9 inhibitor (evolocumab 140 mg every 2 weeks or 420 mg monthly). 4, 3

For primary prevention with LDL-C ≥190 mg/dL on maximal statin intensity, addition of ezetimibe or PCSK9 inhibitor may be considered after evaluating ASCVD risk-reduction benefits, adverse effects, and patient preferences. 1

Monitoring Protocol

Baseline: Obtain fasting lipid panel before initiating statin therapy. 1
Follow-up: Reassess LDL-C 4–12 weeks after initiation or dose change to assess response and adherence. 1, 2
Long-term: Annual lipid monitoring thereafter. 1, 2

Shared Decision-Making Discussion Before Statin Initiation

Before initiating statin therapy, engage in a clinician-patient discussion addressing: 1

Anticipated ASCVD risk-reduction benefits (approximately 24–25% relative risk reduction per 39 mg/dL LDL-C reduction) 1
Potential adverse effects (myalgias, new-onset diabetes, drug-drug interactions) 1
Patient preferences, treatment goals, and healthy lifestyle habits 1

Critical Pitfalls to Avoid

Do not withhold statin therapy based solely on age – older adults derive greater absolute benefit due to higher baseline ASCVD risk. 1, 2
Do not use low-intensity statins in diabetic patients – not recommended at any age. 2
Do not calculate 10-year ASCVD risk for patients with LDL-C ≥190 mg/dL – they require immediate high-intensity therapy regardless of risk score. 1
Do not fail to initiate statins in all diabetic adults aged 40–75 years – this is a Class I, Level A recommendation with documented 9% reduction in all-cause mortality and 13% reduction in vascular mortality per 39 mg/dL LDL-C reduction. 2
Do not discontinue statins in patients >75 years already tolerating therapy – continuation is reasonable and recommended. 1, 2

How should I evaluate atherosclerotic cardiovascular disease (ASCVD) risk in an adult patient and determine the appropriate preventive therapy, including statin intensity and additional lipid‑lowering agents?

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