When should a patient start statin therapy?

When to Start Statin Therapy

Initiate statin therapy based on the patient's clinical category: immediately start high-intensity statins for all patients with established ASCVD or LDL-C ≥190 mg/dL; start moderate-to-high intensity statins for patients with diabetes aged 40-75 years; and for primary prevention without diabetes, start statins when 10-year ASCVD risk is ≥7.5% after a risk discussion, with coronary artery calcium scoring to refine decisions when uncertainty exists. 1, 2

Immediate Statin Initiation (No Risk Calculation Needed)

Secondary Prevention - Established ASCVD

• Start high-intensity statin therapy immediately for all patients with clinical ASCVD (prior MI, stroke, TIA, peripheral arterial disease, or coronary revascularization), regardless of age or baseline LDL-C level 1, 2
• Target LDL-C reduction of ≥50% from baseline 1
• If high-intensity statin is not tolerated, use maximally tolerated moderate-intensity statin 2

Severe Primary Hypercholesterolemia

• Start maximally tolerated statin therapy (preferably high-intensity) immediately for LDL-C ≥190 mg/dL without calculating 10-year risk 1, 2
• This population was excluded from most primary prevention trials, making statin therapy a clear indication 1

Diabetes Mellitus (Ages 40-75 Years)

• Start moderate-intensity statin therapy for all patients with diabetes and LDL-C ≥70 mg/dL, without calculating 10-year ASCVD risk 1, 2
• Escalate to high-intensity statin for patients with diabetes who have multiple ASCVD risk factors or are aged 50-75 years 1, 2
• This recommendation reflects the substantially elevated cardiovascular risk in diabetic patients 1

Primary Prevention Based on 10-Year ASCVD Risk

High Risk (≥20% 10-Year ASCVD Risk)

• Start high-intensity statin therapy to reduce LDL-C by ≥50% 1, 2
• The absolute benefit is substantial: preventing major vascular events in approximately 10% of treated patients over 5 years 3

Intermediate Risk (7.5% to <20% 10-Year ASCVD Risk)

• Start moderate-intensity statin therapy to reduce LDL-C by ≥30% after a clinician-patient risk discussion 1, 2
• The USPSTF gives this a Grade B recommendation for ≥10% risk and Grade C for 7.5-10% risk, indicating moderate certainty of at least moderate net benefit 1
• Risk-enhancing factors strengthen the indication for statin therapy in this group 1

Borderline Risk (5% to <7.5% 10-Year ASCVD Risk)

• Consider moderate-intensity statin therapy only when risk-enhancing factors are present 1
• Risk-enhancing factors include: family history of premature ASCVD, persistently elevated LDL-C ≥160 mg/dL, metabolic syndrome, chronic kidney disease, chronic inflammatory disorders (rheumatoid arthritis, psoriasis, HIV), South Asian ancestry, persistent triglycerides ≥175 mg/dL, and if measured: high-sensitivity CRP ≥2.0 mg/L, ABI <0.9, or lipoprotein(a) ≥50 mg/dL 1, 2

Low Risk (<5% 10-Year ASCVD Risk)

• Prioritize lifestyle modification and address individual risk factors 1
• Statin therapy is generally not indicated unless severe hypercholesterolemia is present 1

Using Coronary Artery Calcium (CAC) Scoring to Refine Decisions

When the decision about statin therapy is uncertain in intermediate-risk (7.5-19.9%) or selected borderline-risk (5-7.5%) patients, measure CAC score to personalize the recommendation: 1, 2

CAC Score = 0

• Withhold statin therapy and reassess in 5-10 years, except in patients with diabetes, cigarette smoking, or strong family history of premature CHD 1, 2
• A zero CAC score substantially reduces near-term risk, though family history may attenuate this benefit 2, 4

CAC Score 1-99

• Initiate statin therapy, especially for patients ≥55 years of age 1
• This score indicates subclinical atherosclerosis warranting treatment 4

CAC Score ≥100 or ≥75th Percentile

• Initiate statin therapy unless deferred after clinician-patient risk discussion 1, 2
• CAC ≥300 Agatston units reclassifies patients to high risk 5, 6
• CAC scoring reclassifies risk in approximately 50% of intermediate-risk patients, with a number needed to screen of 14.7 to identify one person warranting statin therapy 6

Special Populations

Adults >75 Years

• Continue statin therapy if already taking it for established ASCVD 2
• For primary prevention in adults >75 years without ASCVD, initiate moderate-intensity statin only after discussing potential benefits and risks 2
• The USPSTF found insufficient evidence to assess the balance of benefits and harms in adults ≥76 years for primary prevention 1
• Consider stopping statin therapy when functional decline, multimorbidity, frailty, or reduced life expectancy limits potential benefits 2

Young Adults (20-39 Years)

• Prioritize estimating lifetime risk and promoting healthy lifestyle 1
• Reserve drug therapy only for select patients with LDL-C ≥160 mg/dL (moderately high) or ≥190 mg/dL (very high) 1

The Clinician-Patient Risk Discussion

Before initiating statin therapy for primary prevention, conduct a risk discussion that includes: 1, 2

• Review of major risk factors (smoking, elevated blood pressure, LDL-C, hemoglobin A1C if indicated, calculated 10-year ASCVD risk) 1
• Presence of risk-enhancing factors 1
• Potential benefits of lifestyle modifications and statin therapy 1
• Potential adverse effects and drug-drug interactions 1
• Cost considerations 1
• Patient preferences and values in shared decision-making 1

This discussion is particularly important for borderline-risk and lower intermediate-risk patients where the absolute benefit is smaller 1

Monitoring After Initiation

• Obtain baseline lipid profile before starting therapy 2
• Reassess lipid profile 4-12 weeks after initiation or dose adjustment to assess adherence and percentage LDL-C reduction 1, 2, 7
• Repeat lipid measurements every 3-12 months as needed 1, 2
• If LDL-C reduction is <30% on moderate-intensity statin, consider increasing to high-intensity statin 7

Common Pitfalls to Avoid

• Do not use low-dose or low-intensity statins when moderate- or high-intensity is indicated—this leaves patients undertreated 2
• Do not withhold statins due to exaggerated concerns about side effects; placebo-controlled trials show that almost all symptomatic adverse events attributed to statins in routine practice are not actually caused by them 3
• Serious adverse events (myopathy, new-onset diabetes, hemorrhagic stroke) are rare: treating 10,000 patients for 5 years causes approximately 5 cases of myopathy, 50-100 new cases of diabetes, and 5-10 hemorrhagic strokes, but prevents 500-1000 major vascular events depending on baseline risk 3
• Do not underestimate cardiovascular risk in patients with prediabetes, obesity, and metabolic syndrome 7