2025 Guidelines for Managing Atherosclerotic Cardiovascular Disease (ASCVD)
The 2025 guidelines for ASCVD management recommend aggressive lipid-lowering therapy with high-intensity statins as first-line treatment, targeting ≥50% LDL-C reduction from baseline with specific goals of <70 mg/dL for primary prevention and <55 mg/dL for secondary prevention. 1
Primary Prevention Strategies
Risk Stratification by Age Group
| Age Group | Recommendations |
|---|---|
| 20-39 years | Consider statin therapy if additional ASCVD risk factors present [1] |
| 40-75 years | Use high-intensity statin in those with ≥1 ASCVD risk factor, targeting LDL-C <70 mg/dL [1] |
| >75 years | Continue current statin therapy or consider initiating moderate-intensity statin after weighing benefits/risks [1] |
High-Intensity Statin Options
- Atorvastatin 40-80 mg (reduces LDL-C by ≥50%)
- Rosuvastatin 20-40 mg (reduces LDL-C by ≥50%) 1
Moderate-Intensity Statin Options
- Atorvastatin 10-20 mg (reduces LDL-C by 30-49%)
- Rosuvastatin 5-10 mg (reduces LDL-C by 30-49%)
- Simvastatin 20-40 mg (reduces LDL-C by 30-49%)
- Pravastatin 40-80 mg (reduces LDL-C by 30-49%) 1
Secondary Prevention (Established ASCVD)
For patients with established ASCVD, the 2025 guidelines recommend:
- High-intensity statin therapy to reduce LDL-C by ≥50% from baseline
- Target LDL-C goal of <55 mg/dL (<1.4 mmol/L) 1
- Add ezetimibe or PCSK9 inhibitor if LDL-C goals not met on maximum tolerated statin therapy 1
Alternative Treatments for Statin Intolerance
For patients who cannot tolerate statins, the guidelines recommend:
- PCSK9 inhibitor with monoclonal antibody treatment
- Bempedoic acid
- PCSK9 inhibitor with siRNA inclisiran 1
Special Populations
Type 1 Diabetes
- Limited clinical trial evidence exists
- Similar statin treatment approaches should be considered as for type 2 diabetes
- For patients <40 years with type 1 diabetes and other ASCVD risk factors, consider moderate-intensity statin therapy 1
Elderly Patients (>75 years)
- Reasonable to continue statin therapy if already on treatment
- May consider initiating moderate-intensity statin after discussing benefits and risks 1
- Requires careful consideration of benefit-risk ratio 2
Monitoring and Follow-up
- Check LDL-C levels 4-12 weeks after initiating therapy to assess response 2
- Target reduction should be ≥50% from baseline for high-intensity therapy 1
- Monitor for muscle pain, weakness, or other adverse effects 2
- Check CK levels if muscle symptoms develop 2
PCSK9 Inhibitors
The 2025 guidelines highlight two approaches to PCSK9 inhibition:
Monoclonal antibodies (evolocumab and alirocumab):
- Reduce LDL-C by 60% when added to maximum tolerated statin
- Reduce major adverse cardiovascular events by 15-20% 1
siRNA therapy (inclisiran):
- Reduces LDL-C by 49-52%
- Less frequent administration (day 1, day 90, then every 6 months)
- Cardiovascular outcome trials are ongoing 1
Pitfalls and Caveats
- Low-dose statin therapy is generally not recommended in people with diabetes but may be the only dose some individuals can tolerate 1
- Statin therapy is contraindicated in pregnancy due to potential teratogenic effects 2
- There is a small increased risk of new-onset diabetes with statin use, but cardiovascular benefits significantly outweigh this risk 2
- For patients with severe renal impairment (CrCl <30 mL/min), lower starting doses are recommended 2
Conclusion
The 2025 ASCVD management guidelines emphasize aggressive lipid-lowering therapy with specific LDL-C goals based on risk stratification. High-intensity statins remain the cornerstone of therapy, with non-statin agents recommended for those who don't achieve target LDL-C levels despite maximum tolerated statin therapy or for those with statin intolerance.