Who should be considered for statin (HMG-CoA reductase inhibitor) therapy?

Who Should Be on a Statin

All adults aged 40-75 years with clinical ASCVD, LDL-C ≥190 mg/dL, or diabetes should be on statin therapy immediately without further risk assessment, and adults aged 40-75 years with LDL-C 70-189 mg/dL and ≥7.5% 10-year ASCVD risk should also receive statins after risk discussion. 1, 2

Four Primary Statin Benefit Groups

The 2018 ACC/AHA guidelines define four clear categories where statin therapy provides proven benefit 1:

1. Secondary Prevention (Clinical ASCVD)

• All patients with established ASCVD (history of MI, acute coronary syndrome, stable/unstable angina, coronary revascularization, stroke, TIA, or peripheral arterial disease) should receive high-intensity statin therapy (≥50% LDL-C reduction) if ≤75 years old 1, 2
• For patients >75 years with ASCVD, moderate-intensity statin therapy (30-49% LDL-C reduction) is recommended, with continuation reasonable if already tolerating therapy 1

2. Severe Hypercholesterolemia (LDL-C ≥190 mg/dL)

• All adults aged 20-75 years with LDL-C ≥190 mg/dL should receive maximally tolerated statin therapy (preferably high-intensity) regardless of calculated ASCVD risk 1, 3
• This threshold identifies likely familial hypercholesterolemia requiring aggressive intervention 2, 4

3. Diabetes Mellitus

• All adults aged 40-75 years with diabetes should receive at least moderate-intensity statin therapy regardless of baseline LDL-C or calculated 10-year ASCVD risk 1
• High-intensity statin therapy is reasonable for diabetic patients with multiple ASCVD risk factors 1
• For diabetic patients aged 20-39 years, consider moderate-intensity statins if they have: ≥10 years of type 2 diabetes, ≥20 years of type 1 diabetes, albuminuria ≥30 mcg/mg, eGFR <60 mL/min/1.73 m², retinopathy, neuropathy, or ABI <0.9 1, 2

4. Primary Prevention Based on 10-Year ASCVD Risk

• Adults aged 40-75 years with LDL-C 70-189 mg/dL and ≥7.5% 10-year ASCVD risk (calculated using Pooled Cohort Equations) should receive moderate-to-high intensity statin therapy after clinician-patient risk discussion 1
• The USPSTF 2022 recommendation requires ≥10% 10-year risk PLUS ≥1 CVD risk factor (dyslipidemia, diabetes, hypertension, or smoking) for a Grade B recommendation 1, 5
• For patients with 5-7.5% 10-year risk, statins may be considered selectively based on risk-enhancing factors 1

Risk-Enhancing Factors for Borderline/Intermediate Risk

When 10-year ASCVD risk is 5-19.9% (borderline or intermediate), consider these factors to guide statin initiation 1, 2:

• Family history of premature ASCVD (male first-degree relative <55 years, female <65 years) 1
• Primary LDL-C ≥160 mg/dL or other evidence of genetic hyperlipidemia 1
• Chronic kidney disease (eGFR <60 mL/min/1.73 m² without dialysis) 1, 2
• Metabolic syndrome 1
• High-sensitivity CRP ≥2.0 mg/L 1, 6
• Ankle-brachial index <0.9 1, 6
• Lipoprotein(a) ≥50 mg/dL 1
• Elevated apolipoprotein B 1
• Persistent triglycerides ≥175 mg/dL 1
• History of preeclampsia or premature menopause (<40 years) in women 1
• Inflammatory conditions (rheumatoid arthritis, psoriasis, HIV) 1

Coronary Artery Calcium (CAC) Scoring for Uncertain Risk

CAC scoring is the single most useful test when treatment decision is uncertain in patients with 5-20% 10-year ASCVD risk 1, 4:

• CAC = 0: Reasonable to withhold statin therapy and reassess in 5-10 years, unless diabetes, family history of premature CHD, or current smoking present 1, 2, 4
• CAC = 1-99: Consider statin therapy, especially if ≥55 years 4
• CAC ≥100 or ≥75th percentile for age/sex/ethnicity: Initiate statin therapy 1, 4
• CAC ≥300 Agatston units: Strong indication for statin therapy 1, 6

Special Populations

Adults >75 Years

• Continue statins if already taking and tolerating them 1
• For secondary prevention, moderate-intensity statin therapy is reasonable 1
• For primary prevention initiation, evidence is insufficient; decision requires individualized assessment of comorbidities, life expectancy, and patient preferences 1, 5

Young Adults (20-39 Years)

• Generally at low 10-year risk; focus on lifetime risk assessment and lifestyle modification 1
• Consider statins only for: LDL-C ≥190 mg/dL, diabetes with complications (see above), or familial hypercholesterolemia 1

Asian Patients

• Initiate at 5 mg rosuvastatin (or equivalent) due to higher myopathy risk 7
• Consider risks/benefits if not controlled at doses up to 20 mg daily 7

Severe Renal Impairment (Not on Hemodialysis)

• Initiate at 5 mg rosuvastatin; do not exceed 10 mg daily 7

Statin Intensity Definitions

High-intensity statins (≥50% LDL-C reduction) 1, 3:

• Atorvastatin 40-80 mg
• Rosuvastatin 20-40 mg

Moderate-intensity statins (30-49% LDL-C reduction) 1, 3:

• Atorvastatin 10-20 mg
• Rosuvastatin 5-10 mg
• Simvastatin 20-40 mg
• Pravastatin 40-80 mg
• Lovastatin 40 mg
• Fluvastatin 80 mg
• Pitavastatin 1-4 mg

Common Pitfalls to Avoid

• Do not wait for LDL-C to reach specific thresholds in the four primary benefit groups—these patients need statins regardless of baseline LDL-C 1, 3
• Do not use "treat-to-target" LDL-C goals as primary strategy; focus on appropriate statin intensity for risk category 1
• Do not overlook younger diabetic patients (20-39 years) with long disease duration or complications 1, 2
• Do not automatically prescribe statins to all patients >75 years for primary prevention without considering comorbidities and life expectancy 1
• Recognize that Pooled Cohort Equations may overestimate risk in some populations; use CAC scoring when uncertain 1, 4
• Do not forget shared decision-making for primary prevention patients, especially those with 7.5-10% 10-year risk 1

Monitoring After Initiation

• Reassess lipid profile 4-12 weeks after starting therapy to verify adherence and adequate LDL-C reduction 1, 2, 3
• Evaluate for percentage reduction in LDL-C rather than absolute values 3
• If inadequate response, assess adherence, consider dose adjustment, or evaluate for secondary causes of hyperlipidemia 3