First-Line Treatment for High Cholesterol
Statins are the first-line therapy for adults with elevated LDL-cholesterol, with treatment intensity determined by the presence of atherosclerotic cardiovascular disease (ASCVD), diabetes, baseline LDL-C level, and 10-year ASCVD risk. 1
Treatment Algorithm by Clinical Category
Patients with Clinical ASCVD (Secondary Prevention)
High-intensity statin therapy should be initiated or continued in all women and men ≤75 years with clinical ASCVD unless contraindicated. 1 High-intensity statins include atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily, which provide ≥50% LDL-C reduction. 1
When high-intensity statin therapy is contraindicated or not tolerated, moderate-intensity statin therapy should be used as the second option. 1 Moderate-intensity options include atorvastatin 10-20 mg, rosuvastatin 5-10 mg, simvastatin 20-40 mg, or pravastatin 40-80 mg daily. 1
For patients >75 years with clinical ASCVD, it is reasonable to evaluate potential benefits versus adverse effects and continue statin therapy in those tolerating it, or initiate moderate- to high-intensity statin after shared decision-making. 1
Primary Prevention: LDL-C ≥190 mg/dL
Adults ≥21 years with primary LDL-C ≥190 mg/dL should be treated with high-intensity statin therapy unless contraindicated, without requiring 10-year ASCVD risk calculation. 1 This threshold identifies patients with likely genetic hypercholesterolemia who benefit from aggressive early treatment. 1
For individuals unable to tolerate high-intensity statin therapy, use the maximum tolerated statin intensity. 1
After initiating statin therapy, it is reasonable to intensify treatment to achieve at least 50% LDL-C reduction from baseline. 1
Primary Prevention: Diabetes (Age 40-75 Years)
Moderate-intensity statin therapy should be initiated or continued for all adults 40-75 years with diabetes. 1 This recommendation applies regardless of baseline LDL-C level, as diabetes itself confers high cardiovascular risk. 1
High-intensity statin therapy is reasonable for adults 40-75 years with diabetes and ≥7.5% estimated 10-year ASCVD risk. 1
For adults with diabetes who are <40 years or >75 years, it is reasonable to evaluate potential ASCVD benefits versus adverse effects when deciding to initiate, continue, or intensify statin therapy. 1
Primary Prevention: No Diabetes, LDL-C 70-189 mg/dL
The Pooled Cohort Equations should be used to estimate 10-year ASCVD risk to guide statin initiation. 1 This risk calculator incorporates age, sex, race, total cholesterol, HDL-C, systolic blood pressure, treatment for hypertension, diabetes status, and smoking status. 1
Adults 40-75 years with LDL-C 70-189 mg/dL and ≥7.5% 10-year ASCVD risk should be treated with moderate- to high-intensity statin therapy. 1 This represents the primary prevention threshold where statin benefit clearly outweighs risk. 1
For adults 40-75 years with LDL-C 70-189 mg/dL and 5% to <7.5% 10-year ASCVD risk, a clinician-patient discussion is recommended before initiating statin therapy. 1 Risk-enhancing factors should be considered, including family history of premature ASCVD, persistently elevated LDL-C ≥160 mg/dL, chronic kidney disease, metabolic syndrome, inflammatory conditions, premature menopause, preeclampsia, high-risk ethnicity, persistently elevated triglycerides ≥175 mg/dL, or elevated high-sensitivity C-reactive protein ≥2 mg/L. 1
Coronary artery calcium (CAC) scoring may be considered in intermediate-risk patients when uncertainty exists about statin benefit. 1 CAC=0 suggests statin therapy may be deferred (except in diabetes, family history of premature ASCVD, or cigarette smoking), while CAC ≥100 or ≥75th percentile strongly favors statin initiation. 1
Why Statins Are First-Line
Statins reduce major adverse cardiovascular events by approximately 20-25% per 1.0 mmol/L (39 mg/dL) LDL-C reduction, with this benefit demonstrated across multiple large randomized controlled trials. 2, 3 This represents the strongest evidence base of any lipid-lowering therapy. 2
Statins reduce cardiovascular mortality and all-cause mortality in both primary and secondary prevention populations. 2, 4 Meta-analyses in diabetic patients show 9% reduction in all-cause mortality and 13% reduction in vascular mortality per 39 mg/dL LDL-C decrease. 2
The absolute benefit of statin therapy is proportional to baseline ASCVD risk, making risk-based treatment decisions more effective than treating based solely on LDL-C thresholds. 1
When to Add Non-Statin Therapy
Ezetimibe 10 mg daily should be added if LDL-C targets are not reached with maximally tolerated statin therapy. 1 Ezetimibe provides an additional 15-20% LDL-C reduction and has proven cardiovascular benefit when added to statins. 1
PCSK9 inhibitors (evolocumab or alirocumab) are recommended for patients at very high cardiovascular risk with persistent high LDL-C despite maximal tolerated statin plus ezetimibe, or in patients with statin intolerance. 1, 5, 3 These agents reduce LDL-C by approximately 50-60% and have demonstrated cardiovascular event reduction in outcome trials. 5, 3
The Expert Panel found no data supporting routine use of non-statin drugs combined with statin therapy to further reduce ASCVD events beyond what is achieved with appropriate-intensity statin therapy alone. 1 Non-statin agents should be reserved for high-risk patients who cannot achieve adequate LDL-C reduction with statins or who are statin-intolerant. 1
Critical Pitfalls to Avoid
Do not use LDL-C targets or percent reductions as performance measures, as no evidence supports titrating therapy to specific LDL-C goals improves outcomes compared to using guideline-recommended statin intensity. 1 The focus should be on prescribing the appropriate intensity of statin based on clinical category, not on achieving arbitrary LDL-C numbers. 1
Do not delay statin initiation in high-risk patients while attempting lifestyle modifications alone. 1 Lifestyle changes and statin therapy should be implemented concurrently in patients with clinical ASCVD, diabetes, LDL-C ≥190 mg/dL, or ≥7.5% 10-year ASCVD risk. 1
Do not prescribe statins to women of childbearing potential without adequate contraception, as statins are contraindicated in pregnancy. 1
Do not overlook secondary causes of hyperlipidemia before initiating therapy. 1 Evaluate for hypothyroidism, nephrotic syndrome, obstructive liver disease, medications (thiazides, glucocorticoids, amiodarone, cyclosporine), and excessive alcohol intake. 1