What are the recommended management strategies for patients with Atherosclerotic Cardiovascular Disease (ASCVD)?

Recommended Management Strategies for ASCVD

All patients with established ASCVD should receive high-intensity statin therapy targeting LDL cholesterol reduction of ≥50% from baseline to a goal of <55 mg/dL (<1.4 mmol/L), with addition of ezetimibe or PCSK9 inhibitors if targets are not met on maximum tolerated statin therapy. 1

Lipid Management: The Cornerstone of ASCVD Treatment

High-Intensity Statin Therapy

• Start high-intensity statin therapy immediately in all ASCVD patients ≤75 years of age, using atorvastatin 40-80 mg or rosuvastatin 20-40 mg to achieve ≥50% LDL-C reduction 1, 2
• For patients >75 years, use moderate-intensity statin therapy, though high-intensity can be considered after evaluating frailty, drug interactions, and potential adverse effects 1, 3
• The goal is LDL cholesterol <55 mg/dL (<1.4 mmol/L), which represents the most aggressive target based on recent evidence showing maximal cardiovascular benefit 1

Intensification Strategy When Targets Are Not Met

• Add ezetimibe 10 mg daily if LDL cholesterol remains elevated despite maximum tolerated statin therapy 1
• Ezetimibe provides an additional 18-25% LDL-C reduction and demonstrated cardiovascular benefit in the IMPROVE-IT trial when added to moderate-intensity statins 1
• Add PCSK9 inhibitor (evolocumab or alirocumab) if LDL cholesterol ≥70 mg/dL despite maximally tolerated statin plus ezetimibe 1, 4
• PCSK9 inhibitors reduce LDL cholesterol by 60% and decrease major adverse cardiovascular events by 15-20% in the FOURIER and ODYSSEY OUTCOMES trials 1

Alternative Approaches for Statin Intolerance

• Combine moderate-intensity statin with ezetimibe rather than discontinuing therapy entirely, as this provides comparable efficacy with better tolerability 5
• Consider bempedoic acid as an alternative LDL-lowering agent for statin-intolerant patients 1
• Use inclisiran (siRNA PCSK9 inhibitor) administered every 6 months for patients requiring less frequent dosing, which reduces LDL cholesterol by 49-52% 1
• Even extremely low or less-than-daily statin doses provide cardiovascular benefit and should be attempted before complete discontinuation 4

Special Considerations for Diabetic Patients with ASCVD

Mandatory High-Intensity Therapy

• All diabetic patients with ASCVD require high-intensity statin therapy regardless of baseline LDL levels, as every 39 mg/dL reduction in LDL cholesterol produces a 21% reduction in major cardiovascular events 4
• Very high-risk diabetic patients (those with recent acute coronary syndrome or multiple vascular beds involved) should target LDL <55 mg/dL with >50% reduction from baseline 4

Glucose-Lowering Agents with Cardiovascular Benefit

• Add SGLT2 inhibitor for all diabetic patients with ASCVD and eGFR ≥20 mL/min/1.73 m², independent of glycemic control 1
• Add GLP-1 receptor agonist with demonstrated cardiovascular benefit as part of comprehensive risk reduction 1
• These agents provide organ protection beyond glucose lowering and should be initiated regardless of HbA1c targets or metformin use 1

Blood Pressure Management

• Target blood pressure <130/80 mmHg in all ASCVD patients 3
• Initiate appropriate antihypertensive therapy based on current guidelines, with particular attention to renin-angiotensin-aldosterone system inhibitors which provide additional cardiovascular protection 6

Antiplatelet Therapy

• Continue evidence-based antiplatelet therapy as part of secondary prevention, with consideration of additional antithrombotic strategies in select high-risk patients 6

Monitoring Protocol

• Obtain lipid panel 4-12 weeks after initiating or changing statin therapy to assess response 3, 4
• Routine monitoring of liver enzymes or creatine kinase is not recommended unless clinically indicated 2
• Reassess lipid panel at least annually once targets are achieved 4

Critical Pitfalls to Avoid

• Never withhold high-intensity statins from ASCVD patients based on "acceptable" baseline LDL levels—the evidence supports aggressive lowering regardless of starting values 4
• Do not use treat-to-target strategies that result in down-titration of evidence-based statin intensity once a goal is reached, as this contradicts RCT evidence 1
• Avoid adding nonstatin therapies without first maximizing statin intensity, unless the patient is truly statin-intolerant 1
• For females of childbearing potential with ASCVD, discuss contraception before initiating statin therapy due to teratogenic effects 4
• Do not assume patients on dialysis will benefit from statin initiation for primary prevention, though secondary prevention benefits persist 1

Lifestyle Modifications

• Prescribe Mediterranean, DASH, or plant-based diet to synergistically lower cholesterol and blood pressure 3
• Recommend 150-300 minutes of moderate-intensity or 75-150 minutes of vigorous-intensity physical activity weekly 3
• Provide smoking cessation counseling with pharmacotherapy (nicotine replacement, varenicline, or bupropion) for all smokers 3