When do you start statins (HMG-CoA reductase inhibitors) in patients?

When to Start Statins

Initiate statin therapy immediately for all patients with established atherosclerotic cardiovascular disease (ASCVD) regardless of age or baseline LDL-C levels, using high-intensity statins; for primary prevention, start statins in all adults with diabetes aged 40-75 years, anyone with LDL-C ≥190 mg/dL, or those aged 40-75 years with ≥7.5% 10-year ASCVD risk. 1, 2

Secondary Prevention (Established ASCVD)

Start high-intensity statin therapy immediately for any patient with clinical ASCVD, which includes:

• History of myocardial infarction or acute coronary syndrome 3, 1
• Prior stroke or transient ischemic attack (non-cardioembolic) 3, 1
• Peripheral arterial disease or carotid artery disease 3, 1
• Prior coronary or arterial revascularization 2

Do not wait for lipid panels or delay treatment—the presence of ASCVD alone mandates immediate statin initiation. 2 Target LDL-C reduction of ≥50% from baseline with an absolute goal <55 mg/dL. 2 Use atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily. 2, 4

For patients already on statins who are >75 years old with established ASCVD, continue therapy—age alone is not a contraindication. 3, 2

Primary Prevention: Diabetes

All adults with diabetes aged 40-75 years require at least moderate-intensity statin therapy, regardless of baseline LDL-C or calculated risk. 3, 1, 2 This is a class A recommendation that does not require risk calculation. 3

• Escalate to high-intensity statin for those with multiple ASCVD risk factors or aged 50-70 years. 3, 2
• For younger patients aged 20-39 with diabetes plus additional ASCVD risk factors (long disease duration ≥10 years type 1 or ≥20 years type 2, albuminuria, eGFR <60, retinopathy, neuropathy), statin initiation is reasonable. 3, 2
• For patients >75 years with diabetes, continue statins if already on therapy; may initiate moderate-intensity after discussing benefits/risks if not currently treated. 3, 2

Primary Prevention: Severe Hypercholesterolemia

Initiate maximally tolerated statin therapy (preferably high-intensity) immediately for adults with LDL-C ≥190 mg/dL without calculating 10-year risk. 1, 2, 5 This represents severe primary hypercholesterolemia or possible familial hypercholesterolemia and warrants aggressive treatment. 2

Primary Prevention: Risk-Based Approach (No Diabetes, LDL-C 70-189 mg/dL)

For adults aged 40-75 without diabetes or severe hypercholesterolemia, use 10-year ASCVD risk estimation to guide therapy: 1, 2

≥20% 10-year ASCVD risk:

• Initiate high-intensity statin therapy to reduce LDL-C by ≥50%. 1, 2, 6

7.5% to <20% 10-year ASCVD risk:

• Initiate moderate-intensity statin therapy to reduce LDL-C by 30-49%. 1, 2, 6
• Consider risk-enhancing factors: family history of premature ASCVD, persistently elevated LDL-C ≥160 mg/dL, chronic kidney disease, metabolic syndrome, inflammatory conditions, South Asian ancestry, premature menopause or preeclampsia history, elevated high-sensitivity C-reactive protein, lipoprotein(a), or apolipoprotein B. 2, 5
• If decision remains uncertain, consider coronary artery calcium (CAC) scoring. 2, 5 If CAC score is zero, it is reasonable to withhold statin therapy and reassess in 5-10 years, unless diabetes, family history of premature CHD, or smoking is present. 5

<7.5% 10-year ASCVD risk:

• Statins generally not indicated unless risk-enhancing factors present. 6

The US Preventive Services Task Force supports statin use for those with ≥10% 10-year risk (B recommendation) and selective use for 7.5-10% risk (C recommendation). 6

Special Populations

Adults >75 years:

• With established ASCVD: Continue moderate- or high-intensity statin therapy if already on it—same recommendations as younger patients. 3, 1, 2
• Without established ASCVD: May initiate moderate-intensity statin after discussing potential benefits and risks, considering functional status, multimorbidity, frailty, and life expectancy. 3, 2, 5 Consider CAC scoring for ages 76-80 to reclassify those with CAC score of zero to avoid statin therapy. 3, 2

Chronic kidney disease (CKD) stage 3-5:

• Initiate statin or statin/ezetimibe combination for patients not undergoing dialysis. 3, 1
• Patients taking statins initiating dialysis: continue statin, especially in ASCVD patients. 3
• Dialysis patients without ASCVD: statins not recommended. 3
• Avoid high-intensity statins in CKD patients with eGFR <60 due to increased myopathy risk. 2

Pregnancy and women of childbearing potential:

• Stop statin therapy 1-2 months before contemplating pregnancy. 3, 1
• Avoid lipid-lowering drugs during pregnancy and breastfeeding. 3, 4

Asian patients:

• Initiate at 5 mg rosuvastatin daily due to higher risk of myopathy. 3, 4
• Consider risks and benefits if not adequately controlled at doses up to 20 mg daily. 3

Children and adolescents:

• Screen as early as age 2 if family history of early CVD or significant hypercholesterolemia to detect familial hypercholesterolemia. 2, 5
• For heterozygous familial hypercholesterolemia aged ≥8 years: start pravastatin 20 mg daily (ages 8-13) or 40 mg daily (ages 14-18), or rosuvastatin 5-10 mg daily (ages 8 to <10) or 5-20 mg daily (ages ≥10). 2, 4
• For homozygous familial hypercholesterolemia aged ≥7 years: rosuvastatin 20 mg daily. 2, 4

Monitoring After Initiation

• Obtain baseline lipid profile immediately before starting therapy. 3, 2, 5
• Reassess lipid profile 4-12 weeks after initiation or any dose change to assess adherence and efficacy. 3, 1, 2, 5
• Continue monitoring annually or every 3-12 months based on need to assess adherence or safety. 3, 2, 5
• Consider testing liver enzymes before initiating therapy and as clinically indicated thereafter. 4

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. 2 The most common error is hesitating to start therapy when clear indications exist.

Do not use low-intensity statins when moderate- or high-intensity is indicated—this leaves patients undertreated and fails to achieve adequate LDL-C reduction. 2, 5

Do not withhold statins in patients >75 years with established ASCVD—age alone is not a contraindication, and these patients derive substantial benefit from continued therapy. 3, 2

Do not stop statins in patients initiating dialysis if they have established ASCVD—continue therapy as benefits persist. 3

Statin Intensity Definitions

• High-intensity: Lowers LDL-C by ≥50% (atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily). 2, 5
• Moderate-intensity: Lowers LDL-C by 30-49% (atorvastatin 10-20 mg daily or rosuvastatin 5-10 mg daily). 2, 5

The evidence from randomized controlled trials demonstrates that statins reduce all-cause mortality (OR 0.86), combined fatal and non-fatal CVD events (RR 0.75), and stroke (RR 0.78) in primary prevention. 7 The risk of serious muscle injury is <0.1%, serious hepatotoxicity ≈0.001%, and new-onset diabetes ≈0.2% per year—risks that are far outweighed by cardiovascular benefits in appropriately selected patients. 8