When should statin (HMG-CoA reductase inhibitor) pharmacotherapy be initiated?

When to Start Statin Pharmacotherapy

Initiate statin therapy immediately for secondary prevention in all patients with established atherosclerotic cardiovascular disease (ASCVD), and for primary prevention based on age, risk factors, and calculated 10-year ASCVD risk using a risk-stratified approach. 1, 2

Secondary Prevention: Start Immediately

For patients with established ASCVD, initiate high-intensity statin therapy as soon as possible, ideally within 24 hours of hospital admission. 1, 2

• Established ASCVD includes: acute coronary syndrome, myocardial infarction, stable or unstable angina, coronary revascularization, stroke, transient ischemic attack, or peripheral artery disease of atherosclerotic origin 1, 2
• For patients ≤75 years with ASCVD: Start high-intensity statin (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) targeting ≥50% LDL-C reduction 1, 2
• For patients >75 years with ASCVD: Initiate moderate- or high-intensity statin after considering frailty, drug interactions, and patient preferences 2
• Do not discontinue statins during hospitalization if already prescribed, as discontinuation increases short-term mortality and adverse cardiac events 1

Primary Prevention: Risk-Stratified Approach

Severe Hypercholesterolemia (LDL-C ≥190 mg/dL)

Start maximally tolerated statin therapy immediately, preferably high-intensity, without calculating 10-year risk. 1, 2, 3

Diabetes Mellitus

For adults aged 40-75 years with diabetes and LDL-C 70-189 mg/dL: 1, 3

• Initiate moderate-intensity statin therapy regardless of calculated 10-year ASCVD risk 1, 3
• Escalate to high-intensity statin for patients with multiple ASCVD risk factors or aged 50-70 years 1, 3

For adults aged 20-39 years with diabetes: It may be reasonable to initiate statin therapy if additional ASCVD risk factors are present 1

Adults Without Diabetes (Ages 40-75 Years)

Calculate 10-year ASCVD risk using the Pooled Cohort Equations and stratify: 1, 2

High Risk (≥20% 10-year ASCVD risk):

• Initiate high-intensity statin targeting ≥50% LDL-C reduction 1, 3

Intermediate Risk (7.5% to <20% 10-year ASCVD risk):

• Initiate moderate-intensity statin targeting ≥30% LDL-C reduction 1, 2
• Consider high-intensity statin if risk-enhancing factors are present (family history of premature ASCVD, primary hypercholesterolemia, metabolic syndrome, chronic kidney disease, South Asian ancestry, persistently elevated triglycerides ≥175 mg/dL, history of preeclampsia) 1, 3

Borderline Risk (5% to <7.5% 10-year ASCVD risk):

• Consider moderate-intensity statin if risk-enhancing factors are present after risk discussion 1

Low Risk (<5% 10-year ASCVD risk):

• Statin therapy generally not indicated 1

Using Coronary Artery Calcium (CAC) Score to Refine Decisions

When the decision about statin therapy remains uncertain in intermediate-risk or selected borderline-risk adults, obtain a CAC score: 1, 2, 3

• CAC score = 0: Reasonable to withhold statin therapy and reassess in 5-10 years, unless diabetes, family history of premature CHD, or smoking is present 1, 2, 3
• CAC score 1-99: Reasonable to initiate statin therapy 1, 2
• CAC score ≥100 or ≥75th percentile: Initiate statin therapy 1, 2, 3

Special Populations

Older Adults (≥75 Years)

Without established ASCVD: 1, 2, 3

• Initiating moderate-intensity statin may be reasonable after discussing potential benefits, risks, frailty, multimorbidity, and life expectancy 1, 2, 3
• Consider CAC scoring in adults 76-80 years; if CAC = 0, may avoid statin therapy 3

With established ASCVD: Continue statin therapy if already prescribed 2, 3

Chronic Kidney Disease

Initiate statin therapy in CKD patients with: 1

• Known coronary artery disease 1
• Diabetes mellitus 1
• Prior ischemic stroke 1
• Estimated 10-year CVD risk >10% 1
• Age ≥50 years (moderate recommendation) 1

For dialysis patients (CKD-5D): Do not initiate statins, but continue if already on therapy 1

Monitoring After Initiation

Obtain lipid profile: 1, 2, 3

• At baseline before starting therapy 1, 3
• 4-12 weeks after initiation or dose adjustment 1, 2, 3
• Every 3-12 months thereafter based on adherence and safety monitoring needs 1, 2, 3

Common Pitfalls to Avoid

• Do not use low-dose or low-intensity statins when moderate- or high-intensity is indicated, as this leaves patients undertreated 3
• Do not delay statin initiation in acute coronary syndrome—start within 24 hours of admission 1, 2
• Do not discontinue statins during hospitalization unless contraindicated 1
• Muscle symptoms without elevated creatine kinase occur at similar rates in statin and placebo groups (<1% difference in randomized trials), suggesting most symptoms are not pharmacologically caused 4
• The risk of serious adverse events is extremely low: rhabdomyolysis <0.1%, serious hepatotoxicity ≈0.001%, new-onset diabetes ≈0.2% per year 4