When to Initiate Anti-Cholesterol Drugs
Statins should be initiated immediately in all patients with established atherosclerotic cardiovascular disease (ASCVD), acute coronary syndrome, or clinical cardiovascular disease, using high-intensity therapy for those ≤75 years of age. 1
Secondary Prevention (Established ASCVD)
Patients with established ASCVD require immediate statin therapy:
High-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) is mandatory for all patients ≤75 years with clinical ASCVD, including those with myocardial infarction, stable or unstable angina, coronary revascularization, stroke, TIA, or peripheral arterial disease. 1
Initiate or continue high-dose statins early after admission in all acute coronary syndrome patients, regardless of baseline LDL-cholesterol values. 1
For patients >75 years with established ASCVD, use moderate-intensity statins as first-line, though high-intensity therapy remains reasonable if tolerated, considering potential adverse effects and drug interactions. 1
Moderate-intensity statins are the alternative for younger patients with contraindications or intolerance to high-intensity regimens. 1
Primary Prevention Based on Risk Stratification
Very High-Risk Patients (initiate statins immediately):
Type 1 diabetes with microalbuminuria or renal disease requires LDL-cholesterol lowering of at least 50% with statins, irrespective of baseline LDL-cholesterol. 1
Type 2 diabetes with CVD, CKD, or age >40 years with additional risk factors warrants statin therapy targeting LDL-cholesterol <1.8 mmol/L (<70 mg/dL). 1
Stage 3-5 chronic kidney disease (non-dialysis) requires statins or statin/ezetimibe combination, as these patients are at high or very high cardiovascular risk. 1
Peripheral arterial disease or carotid artery disease is a very high-risk condition requiring statin therapy. 1
Patients at high or very high cardiovascular risk require statin therapy for primary prevention of stroke. 1
High-Risk Patients:
Adults without established coronary heart disease but at increased cardiovascular risk based on age, high-sensitivity C-reactive protein ≥2 mg/L, and at least one additional cardiovascular risk factor should receive statins. 2
Type 2 diabetes without additional risk factors requires targeting LDL-cholesterol <2.6 mmol/L (<100 mg/dL). 1
LDL-cholesterol ≥165 mg/dL represents significant ASCVD risk and warrants high-intensity statin therapy to achieve at least 50% LDL-cholesterol reduction. 3
LDL-cholesterol ≥190 mg/dL (severe hypercholesterolemia) automatically qualifies for high-intensity statin therapy regardless of other risk factors. 3
Familial Hypercholesterolemia
Heterozygous familial hypercholesterolemia (HeFH):
Adults and pediatric patients ≥8 years require statins as adjunct to diet. 2, 4, 2
Pediatric patients aged 8 to <10 years: 5-10 mg rosuvastatin or 10 mg atorvastatin once daily. 2, 4
Pediatric patients ≥10 years: 5-20 mg rosuvastatin or 10-20 mg atorvastatin once daily. 2, 4
Homozygous familial hypercholesterolemia (HoFH):
Treatment should begin at diagnosis, ideally by age 2 years, with LDL-cholesterol-lowering medications. 1
Pediatric patients ≥7 years: 20 mg rosuvastatin once daily as adjunct to other LDL-cholesterol-lowering therapies. 2
Pediatric patients ≥10 years: 10-80 mg atorvastatin once daily. 4
Special Populations Requiring Dose Modifications
Asian patients should initiate rosuvastatin at 5 mg once daily due to higher risk of myopathy, with careful consideration of risks versus benefits if doses >20 mg daily are needed. 2
Severe renal impairment (not on hemodialysis) requires initiating rosuvastatin at 5 mg once daily, not exceeding 10 mg daily. 2
Dialysis-dependent CKD patients without atherosclerotic CVD should not initiate statins, as evidence does not support benefit in this population. 1
Conditions Where Statins Are NOT Recommended
Heart failure without other indications: Cholesterol-lowering therapy with statins is not recommended (though not harmful) in patients with heart failure absent other indications. 1
Aortic valvular stenosis without coronary artery disease: Cholesterol-lowering treatment is not recommended absent other indications. 1
Autoimmune diseases: Universal use of lipid-lowering drugs is not recommended. 1
Monitoring and Escalation
Assess LDL-cholesterol response 4-12 weeks after initiating therapy, evaluating percentage reduction rather than absolute values. 3
If target 50% reduction is not achieved with maximum tolerated statin, add ezetimibe as next step. 3, 5, 6
For extremely high-risk patients with LDL-cholesterol ≥70 mg/dL despite maximum statin plus ezetimibe, consider PCSK9 inhibitors (number-needed-to-treat <25). 5, 6