What is the appropriate lipid‑lowering regimen for an adult with established coronary artery disease, including statin intensity, LDL‑cholesterol targets, and alternatives for statin intolerance or patients over 75 years?

Lipid Therapy in Coronary Artery Disease

Primary Recommendation: High-Intensity Statin for Age ≤75 Years

For adults ≤75 years with established coronary artery disease, initiate or continue high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) as first-line treatment. 1, 2

• High-intensity statins reduce LDL-C by ≥50% on average and have demonstrated superior reduction in cardiovascular events compared to moderate-intensity therapy 1, 3
• This recommendation applies to all patients with clinical ASCVD, defined as acute coronary syndromes, history of MI, stable or unstable angina, coronary revascularization, stroke, TIA, or peripheral arterial disease 1
• If high-intensity statin is contraindicated or not tolerated, use moderate-intensity statin therapy as second-line option 1, 2

Modified Approach for Age >75 Years

For patients >75 years with established CAD, initiate moderate-intensity statin therapy (atorvastatin 10-20 mg, rosuvastatin 5-10 mg, or simvastatin 20-40 mg daily) after evaluating potential benefits, adverse effects, and drug-drug interactions. 1, 4

• RCT data in patients >75 years showed no clear additional benefit from high-intensity versus moderate-intensity statins 1
• Moderate-intensity statins reduce LDL-C by 30-50%, which is sufficient for most older adults 4
• Continue existing statin therapy in patients already tolerating it at time of 75th birthday 1, 4

LDL-C Targets: The Evidence Gap

No specific LDL-C or non-HDL-C targets are recommended for treatment decisions or titration, as RCTs used fixed-dose regimens rather than treat-to-target strategies. 1

• The 2013 ACC/AHA guidelines explicitly make no recommendations for or against specific LDL-C targets because clinical trials did not test titration to specific goals 1
• However, the most recent 2024 international expert panel recommends targeting LDL-C <55 mg/dL (<1.4 mmol/L) in post-ACS patients to reduce recurrent events 1
• A 2023 head-to-head trial found that treat-to-target strategy (LDL-C 50-70 mg/dL) was noninferior to high-intensity statin for composite cardiovascular outcomes 5

Despite guideline ambiguity, practical target: aim for LDL-C <70 mg/dL or ≥50% reduction from baseline in very high-risk patients. 1, 2

Intensification Strategy for Inadequate Response

If LDL-C remains ≥70 mg/dL after 4-6 weeks on maximally tolerated statin, add ezetimibe 10 mg daily. 1, 2

• Ezetimibe provides an additional 15-20% LDL-C reduction 1, 6
• For very high-risk patients (multiple major ASCVD events or one major event plus multiple high-risk conditions), adding ezetimibe is reasonable when LDL-C ≥70 mg/dL on maximal statin 2

If LDL-C remains ≥70 mg/dL or non-HDL-C ≥100 mg/dL after 4-6 weeks on statin plus ezetimibe, add PCSK9 inhibitor (alirocumab, evolocumab) or inclisiran. 1, 2

• PCSK9 inhibitors are administered as subcutaneous injections every 2-4 weeks 1
• Inclisiran requires subcutaneous injection only twice yearly 1
• This triple therapy approach is reserved for very high-risk patients who fail dual therapy 1, 2

Statin Intolerance Management

For patients with documented statin intolerance (typically statin-associated muscle symptoms), attempt the following sequential strategies: 1, 2

1. Try alternate statin at lower dose: Different statins have varying muscle symptom profiles 1
2. Use moderate-intensity statin if high-intensity not tolerated: Provides substantial benefit with lower adverse effect risk 1
3. Consider non-statin monotherapy if all statins fail:
   • Ezetimibe 10 mg daily as monotherapy 1
   • Bempedoic acid (if available) - particularly useful in patients with diabetes or metabolic syndrome as it may help optimize both LDL-C and glucose control 1
   • PCSK9 inhibitors as monotherapy in severe intolerance 1

Special Populations

Chronic Kidney Disease

For patients with eGFR <60 mL/min/1.73 m², use moderate-intensity statins rather than high-intensity statins. 1, 2

• Prescribing information for atorvastatin requires no dose adjustment for kidney disease 1
• Rosuvastatin prescribing information recommends dose adjustment only when creatinine clearance <30 mL/min/1.73 m² 1

Diabetes and Metabolic Syndrome

In high-risk patients with ASCVD plus diabetes, obesity, pre-diabetes, or metabolic syndrome, consider upfront combination therapy with pitavastatin plus ezetimibe, or lower-dose high-intensity statin (rosuvastatin 20 mg or atorvastatin 40 mg) plus ezetimibe. 1

• This approach reduces new-onset diabetes risk while achieving significant LDL-C reduction 1
• If target not achieved, add bempedoic acid to optimize both LDL-C and glucose parameters 1

Heart Failure with Reduced Ejection Fraction

For ischemic cardiomyopathy with reasonable life expectancy (3-5 years) not already on statin, consider moderate-intensity statin. 2

• This is a Class IIb recommendation (may be considered) 2

Monitoring and Follow-Up

Measure lipid panel 4-6 weeks after initiating or intensifying therapy, then repeat 4-6 weeks after each adjustment until target achieved. 1

• Once stable on therapy, measure lipid panel annually 6
• Monitor for drug-drug interactions, particularly in older patients on multiple medications 2, 4
• Assess for statin-associated muscle symptoms at each visit 2

Critical Pitfalls to Avoid

Do not discontinue statins in patients transitioning to dialysis if already receiving therapy at time of dialysis initiation. 1

• However, do not initiate new statin therapy in patients already on dialysis 1

Do not assume all patients require high-intensity statins regardless of age. 1, 4

• The >75 years population has different risk-benefit profile favoring moderate-intensity 1, 4

Do not delay intensification if targets not met. 1

• Escalate therapy at 4-6 week intervals rather than waiting months 1
• Use standardized discharge letters specifying LDL-C goals and escalation timelines to ensure continuity between hospital and primary care 1