When to Initiate Statin Therapy
Initiate high-intensity statin therapy immediately for all patients with established atherosclerotic cardiovascular disease (ASCVD) regardless of age or baseline LDL-C level. 1, 2
Secondary Prevention (Established ASCVD)
Start high-intensity statin therapy as soon as possible—ideally during hospitalization—for any patient with clinical ASCVD. 1, 2 This includes:
- Acute coronary syndrome or myocardial infarction 1, 2
- Stable or unstable angina 1, 2
- Prior coronary or arterial revascularization 1, 2
- Stroke or transient ischemic attack 1, 2
- Peripheral artery disease or aortic aneurysm of atherosclerotic origin 1, 2
Target ≥50% LDL-C reduction from baseline with an absolute goal of <55 mg/dL. 1 Use atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily. 1 Early initiation after acute events improves cardiovascular outcomes and prevents plaque destabilization. 3
For patients >75 years with established ASCVD, continue statins if already on therapy; do not stop based on age alone. 1, 2 Age is not a contraindication to statin therapy in secondary prevention. 1
Primary Prevention: Immediate Initiation Without Risk Calculation
Severe Hypercholesterolemia (LDL-C ≥190 mg/dL)
Start maximally tolerated statin therapy immediately—preferably high-intensity—without calculating 10-year risk. 1, 2, 4 This severe elevation alone warrants immediate treatment. 1
Diabetes Mellitus
Initiate at least moderate-intensity statin therapy for all adults aged 40-75 years with diabetes, regardless of baseline LDL-C or calculated risk. 1, 4 Do not delay treatment while waiting for risk calculations—diabetes itself is sufficient indication. 1, 4
Escalate to high-intensity statin for patients with diabetes plus multiple ASCVD risk factors, targeting ≥50% LDL-C reduction with goal <70 mg/dL. 1, 4
For younger patients aged 20-39 with diabetes plus additional ASCVD risk factors (family history of premature CHD, smoking, hypertension, dyslipidemia, albuminuria), consider initiating statin therapy. 1, 4
Primary Prevention: Risk-Based Approach (LDL-C 70-189 mg/dL, No Diabetes)
For adults aged 40-75 years without diabetes or severe hypercholesterolemia, calculate 10-year ASCVD risk using the Pooled Cohort Equations. 5, 1
High Risk (≥20% 10-year ASCVD risk)
Initiate high-intensity statin therapy to reduce LDL-C by ≥50%. 5, 1, 4
Intermediate Risk (7.5% to <20% 10-year ASCVD risk)
Initiate moderate-intensity statin therapy to reduce LDL-C by 30-49%. 5, 1, 4
If decision remains uncertain, measure coronary artery calcium (CAC) score: 5, 1
- CAC = 0: Reasonable to withhold statin and reassess in 10 years, unless higher-risk conditions present (diabetes, family history of premature CHD, smoking) 5
- CAC 1-99: Reasonable to initiate statin therapy 5
- CAC ≥100 or ≥75th percentile: Initiate statin therapy 5
Risk-enhancing factors that favor statin initiation in intermediate-risk patients include: 5
- Family history of premature ASCVD
- Persistently elevated LDL-C ≥160 mg/dL
- Chronic kidney disease
- Metabolic syndrome
- Inflammatory conditions (rheumatoid arthritis, psoriasis, HIV)
- South Asian ancestry
- Premature menopause or preeclampsia history
- Elevated high-sensitivity C-reactive protein, lipoprotein(a), or apolipoprotein B
Borderline Risk (5% to <7.5% 10-year ASCVD risk)
In risk discussion, presence of risk-enhancing factors may justify moderate-intensity statin therapy. 5, 4 Consider CAC scoring if decision remains uncertain. 5
Low Risk (<5% 10-year ASCVD risk)
Statin therapy generally not indicated; focus on lifestyle modification. 5
Special Populations
Adults >75 Years (Primary Prevention)
For those without established ASCVD, initiating moderate-intensity statin may be reasonable after discussing potential benefits and risks. 5, 1, 4 Consider functional status, multimorbidity, frailty, and life expectancy. 5
It may be reasonable to measure CAC in adults 76-80 years to reclassify those with CAC score of zero to avoid statin therapy. 5
It may be reasonable to stop statin therapy when functional decline (physical or cognitive), multimorbidity, frailty, or reduced life expectancy limits potential benefits. 5
Chronic Kidney Disease
Initiate statin therapy in patients with eGFR <60 mL/min/1.73 m², particularly those with known heart disease, diabetes, prior stroke, or high 10-year cardiovascular risk. 1, 2, 4 Consider statin/ezetimibe combination based on age and diabetes status. 1 Avoid high-intensity statins due to reduced renal excretion concerns. 1
Children with Familial Hypercholesterolemia
For children ≥8 years with heterozygous familial hypercholesterolemia, start pravastatin 20 mg daily (ages 8-13) or 40 mg daily (ages 14-18). 1 Screen children as early as age 2 if family history of early CVD or significant hypercholesterolemia. 1
Other High-Risk Conditions
Initiate statin therapy immediately after non-cardioembolic ischemic stroke or TIA for prevention of further cardiovascular events. 2
Initiate lipid-lowering therapy in patients with occlusive arterial disease of the lower limbs or carotid artery disease irrespective of plasma lipid levels. 2
Consider moderate-intensity statin therapy in patients with heart failure with reduced ejection fraction attributable to ischemic heart disease. 2
Monitoring After Initiation
Obtain baseline lipid profile immediately before starting therapy. 1, 2, 4
Reassess lipid profile 4-12 weeks after initiation or any dose adjustment to assess adherence and efficacy. 5, 1, 2, 4
Continue monitoring every 3-12 months thereafter based on need to assess adherence or safety. 5, 1
Critical Pitfalls to Avoid
Do not delay statin initiation in established ASCVD or diabetes aged 40-75 while waiting for lipid panels or risk calculations—these conditions alone warrant immediate treatment. 1, 4 Approximately 10% of patients in clinical practice discontinue statins due to subjective complaints, but randomized trials show the difference in muscle symptoms between statin and placebo is <1%. 6 This suggests most muscle symptoms are not pharmacologically caused by the statin. 6
Do not use low-intensity statins when moderate- or high-intensity is indicated—this leaves patients undertreated. 1, 7 The risk of serious muscle injury including rhabdomyolysis is <0.1%, and serious hepatotoxicity is ≈0.001%. 6
Do not withhold statins in patients >75 years with established ASCVD—age alone is not a contraindication. 1, 2 The benefits greatly outweigh risks in patients for whom statin treatment is recommended. 6
If LDL-C remains ≥70 mg/dL on maximally tolerated statin in patients with established ASCVD, add ezetimibe; if still ≥70 mg/dL, consider adding PCSK9 inhibitor. 1 Do not accept residual cardiovascular risk when additional therapies are available. 3