LDL Target for Patients with Non-Obstructive CAD
For patients with non-obstructive coronary artery disease, target an LDL-C level below 70 mg/dL, with consideration for an even more aggressive goal of below 55 mg/dL in very high-risk patients. 1
Primary Treatment Goals
Non-obstructive CAD places patients in a high-risk category requiring aggressive lipid management similar to obstructive disease, as these patients have established atherosclerotic disease. 1
The 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline recommends:
- High-intensity statin therapy targeting ≥50% reduction in LDL-C from baseline (Class 1, Level A) 1
- For very high-risk patients with LDL-C ≥70 mg/dL despite maximally tolerated statin, add ezetimibe (Class 2a, Level B-R) 1
- An LDL-C below 55 mg/dL can be considered in this high-risk population 1
The most recent 2025 AHA/ACC performance measures emphasize that intensive lipid lowering is associated with reduced cardiovascular events, with rates inversely proportional to LDL levels achieved. 1
Treatment Algorithm
Step 1: Initiate high-intensity statin therapy
- Aim for ≥50% LDL-C reduction from baseline 1
- This approach is supported by controlled trials showing reduced adverse cardiovascular events with intensive lipid lowering 1
Step 2: If LDL-C remains ≥70 mg/dL on maximally tolerated statin
- Add ezetimibe to further reduce LDL-C below 70 mg/dL 1
- The addition of nonstatin agents in high-risk patients with persistently elevated LDL-C ≥70 mg/dL further reduces cardiovascular events 1
Step 3: If LDL-C still ≥70 mg/dL on statin plus ezetimibe
- Add a PCSK9 monoclonal antibody (Class 2a, Level A) 1
- This is particularly beneficial for very high-risk patients with LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL 1
Evidence Supporting Lower Targets
The relationship between LDL-C and cardiovascular risk is continuous and log-linear, with no threshold below which further reduction provides no benefit. 1 Studies collectively demonstrate that high-intensity therapies with greater LDL reduction result in lower cardiovascular event rates. 1
Research from the REAL-CAD study suggests that cardiovascular risk decreases monotonically until LDL-C reaches 70 mg/dL, supporting this as a critical threshold. 2 However, the most recent guidelines indicate that even lower targets (below 55 mg/dL) may provide additional benefit in very high-risk patients. 1
Secondary Lipid Targets
If triglycerides are elevated:
- For triglycerides 200-499 mg/dL, target non-HDL-C <130 mg/dL 1
- Consider adding niacin or fibrate therapy after achieving LDL-C goals 1
Common Pitfalls to Avoid
Do not stop at LDL-C <100 mg/dL. Older guidelines recommended this target, but current evidence supports more aggressive goals of <70 mg/dL or even <55 mg/dL for patients with established CAD, including non-obstructive disease. 1
Do not undertitrate statin therapy. The majority of patients not achieving goal are on suboptimal statin doses. 3 Maximally tolerated statin therapy should be attempted before adding additional agents. 1
Do not assume non-obstructive CAD is lower risk. These patients have established atherosclerotic disease and warrant the same aggressive lipid management as those with obstructive disease. 1
Do not ignore the need for combination therapy. If LDL-C remains ≥70 mg/dL on maximally tolerated statin, evidence supports adding ezetimibe and potentially PCSK9 inhibitors. 1