What are the recommended treatments for individuals at high risk of cardiovascular disease?

Recommended Treatments for Individuals at High Risk of Cardiovascular Disease

For individuals at high risk of cardiovascular disease, statin therapy is the cornerstone of treatment, with intensity determined by risk level and specific patient characteristics. 1

Risk Assessment and Treatment Approach

• Cardiovascular risk assessment should guide treatment intensity, with different approaches for primary and secondary prevention 1
• Four major statin benefit groups have been identified where ASCVD risk reduction clearly outweighs adverse event risk:
  1. Secondary prevention in individuals with clinical ASCVD
  2. Primary prevention in individuals with LDL-C ≥190 mg/dL
  3. Primary prevention in individuals with diabetes aged 40-75 years with LDL-C 70-189 mg/dL
  4. Primary prevention in individuals without diabetes aged 40-75 years with LDL-C 70-189 mg/dL and estimated 10-year ASCVD risk ≥7.5% 1

Secondary Prevention (Patients with Established ASCVD)

• High-intensity statin therapy should be initiated or continued in patients ≤75 years with clinical ASCVD to achieve ≥50% reduction in LDL-C levels 1
• Moderate-intensity statin therapy is recommended for patients >75 years or those with safety concerns 1
• For very high-risk patients with ASCVD who have LDL-C ≥70 mg/dL despite maximally tolerated statin therapy, consider adding ezetimibe 1
• PCSK9 inhibitors may be considered for very high-risk patients not achieving adequate LDL-C reduction with maximally tolerated statin plus ezetimibe, though cost considerations favor ezetimibe as the first add-on therapy 1

Primary Prevention

Individuals with LDL-C ≥190 mg/dL

• High-intensity statin therapy is recommended to achieve at least a 50% reduction in LDL-C 1
• Non-statin therapies may be considered if additional LDL-C lowering is needed 1

Individuals with Diabetes (Age 40-75 years, LDL-C 70-189 mg/dL)

• Moderate-intensity statin therapy is recommended for all patients in this category 1
• High-intensity statin therapy should be considered for those with estimated 10-year ASCVD risk ≥7.5% 1
• For patients with multiple ASCVD risk factors or aged 50-70 years, high-intensity statin therapy is reasonable 1

Individuals without Diabetes (Age 40-75 years, LDL-C 70-189 mg/dL)

• Estimate 10-year ASCVD risk using the Pooled Cohort Equations 1
• Moderate to high-intensity statin therapy is recommended for those with 10-year ASCVD risk ≥7.5% 1
• For those with 10-year risk of 5% to <7.5%, moderate-intensity statin therapy may be considered 1

Statin Intensity Guidelines

High-Intensity Statin Therapy (lowers LDL-C by ≥50%)

• Atorvastatin 40-80 mg
• Rosuvastatin 20-40 mg 1

Moderate-Intensity Statin Therapy (lowers LDL-C by 30-49%)

• Atorvastatin 10-20 mg
• Rosuvastatin 5-10 mg
• Simvastatin 20-40 mg
• Pravastatin 40-80 mg
• Lovastatin 40 mg
• Fluvastatin XL 80 mg
• Pitavastatin 1-4 mg 1

Special Populations

Chronic Kidney Disease (CKD)

• Patients with stage 3-5 CKD are considered at high or very high CV risk 1
• Statin or statin/ezetimibe combination is indicated in patients with non-dialysis-dependent CKD 1
• In dialysis-dependent CKD patients without atherosclerotic CVD, statins should not be initiated 1

Peripheral Arterial Disease (PAD)

• PAD is considered a very high-risk condition, and lipid-lowering therapy (mostly statins) is strongly recommended 1

Stroke Prevention

• Intensive statin therapy is recommended for patients with a history of non-cardioembolic ischemic stroke or TIA 1

Combination Therapy Considerations

• For patients at very high risk with inadequate LDL-C reduction on maximally tolerated statin therapy, adding ezetimibe is reasonable 1
• Recent evidence supports upfront combination therapy with statin and ezetimibe in high-risk patients, showing reduced cardiovascular events and mortality compared to statin monotherapy alone 1
• Fixed-dose combination (FDC) therapy may improve adherence and efficacy compared to separate pill formulations 1

Monitoring and Safety

• Regular monitoring for adherence to therapy is essential 1
• A fasting lipid panel should be obtained after initiation or changes in therapy 1
• Percentage reductions in LDL-C should be used to assess adherence rather than as treatment goals 1
• Common adverse effects of statins include myalgia, elevated liver enzymes, and increased risk of diabetes 2
• For patients with less-than-anticipated response or statin intolerance, consider:
  • Reassessing adherence
  • Excluding secondary causes of hyperlipidemia
  • Adjusting statin dose or switching to another statin
  • Adding non-statin therapy 1

Common Pitfalls to Avoid

• Underutilization of high-intensity statin therapy in appropriate patients 3, 4
• Premature discontinuation of statin therapy due to perceived side effects 5
• Failure to consider combination therapy when LDL-C goals are not achieved with statin monotherapy 4
• Overreliance on treating to specific LDL-C targets rather than using appropriate intensity statin therapy based on risk 1
• Inadequate attention to lifestyle modifications, which remain crucial alongside pharmacotherapy 1

Remember that lifestyle modification (heart-healthy diet, regular exercise, smoking cessation, and weight management) remains a crucial component of cardiovascular risk reduction and should be emphasized alongside pharmacological therapy 1.