LDL Cholesterol Targets for Secondary Prevention After Myocardial Infarction
For patients with prior MI, initiate high-intensity statin therapy immediately to achieve an LDL-C <70 mg/dL (<1.8 mmol/L) with at least a 50% reduction from baseline, and if this target is not met on maximal statin therapy, add ezetimibe to further lower LDL-C. 1
Primary LDL-C Target
The target LDL-C level is <70 mg/dL (<1.8 mmol/L) OR a ≥50% reduction from baseline LDL-C levels. 2
The most recent 2025 guidelines from the American College of Cardiology recommend an even more aggressive target of LDL-C <55 mg/dL (<1.4 mmol/L) with at least a 50% reduction from baseline for patients with established coronary heart disease, who are classified as "very high risk." 1
The European Society of Cardiology guidelines similarly recommend LDL-C <1.8 mmol/L (~70 mg/dL) or a ≥50% LDL-C reduction when the target level cannot be reached for patients at very high cardiovascular disease risk. 2
Every 1.0 mmol/L reduction in LDL-C is associated with a 20-25% reduction in cardiovascular mortality and non-fatal myocardial infarction. 2
Treatment Algorithm
Step 1: Initiate High-Intensity Statin Therapy
Start high-intensity statin therapy before hospital discharge in all post-MI patients. 2, 1
High-intensity statins include atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily. 1
Statins should be initiated while the patient is still hospitalized after an acute coronary syndrome. 2
The goal is to achieve at least a 30-40% reduction in LDL-C levels, though ≥50% reduction is preferred. 2
Step 2: Assess Lipid Levels
Obtain fasting lipid levels within 24 hours of hospitalization for MI and reassess within 1 year after discharge. 2, 3
- Baseline LDL-C levels should be documented before initiating therapy to calculate the percentage reduction achieved. 2
Step 3: Add Ezetimibe if Target Not Achieved
If LDL-C remains >70 mg/dL on maximal statin therapy, add ezetimibe 10 mg daily. 2, 1
The addition of ezetimibe is reasonable (Class IIa recommendation) when LDL-C >70 mg/dL despite maximal statin therapy. 2
The American College of Cardiology recommends adding ezetimibe before considering PCSK9 inhibitors. 1
Only 1.9% of post-MI patients receive ezetimibe despite many failing to reach LDL-C goals on statin monotherapy alone. 3
Step 4: Consider PCSK9 Inhibitors for Very High-Risk Patients
If LDL-C remains >70 mg/dL despite maximal statin plus ezetimibe therapy, adding a PCSK9 inhibitor (evolocumab or alirocumab) is reasonable. 2, 1
This applies particularly to patients at "very high risk," defined as those with multiple major ASCVD events or one major ASCVD event plus multiple high-risk conditions. 2, 1
PCSK9 inhibitors should only be added after maximizing statin and ezetimibe therapy. 1
Evidence Supporting the <70 mg/dL Target
Achieving LDL-C <70 mg/dL is associated with the lowest risk of recurrent cardiovascular events in secondary prevention populations. 2
A 2022 meta-analysis of 130,070 patients demonstrated that achieving LDL-C <70 mg/dL (median 62 mg/dL) versus ≥70 mg/dL (median 103 mg/dL) significantly reduced all-cause mortality, cardiovascular mortality, myocardial infarction, cerebrovascular events, and revascularization without increasing cancer, diabetes, or hemorrhagic stroke risk. 4
A 2015 real-world study found that achieving ≥50% LDL-C reduction from baseline was associated with a 47% risk reduction in major cardiac events (adjusted HR 0.53,95% CI 0.36-0.79, P=0.002), whereas simply achieving <70 mg/dL without considering percentage reduction showed no significant benefit. 5
A 2022 Japanese study suggested that cardiovascular event risk decreased monotonically until LDL-C reached 70 mg/dL, but further reduction below this threshold did not provide additional benefit, suggesting 70 mg/dL may represent an optimal target. 6
Secondary Target: Non-HDL Cholesterol
If triglycerides are ≥200 mg/dL, the non-HDL-C target should be <130 mg/dL (or <100 mg/dL as a more aggressive goal). 2
The 2025 guidelines recommend a secondary target of non-HDL-C <85 mg/dL (<2.2 mmol/L) for very high-risk patients. 1
Non-HDL-C is calculated as total cholesterol minus HDL-C. 2
Common Pitfalls and Caveats
Despite guideline recommendations, LDL-C goal attainment rates remain suboptimal in clinical practice. 3, 7
Only 36.9% of post-MI patients achieved the 2016 ESC/EAS target of LDL-C <70 mg/dL with ≥50% reduction, and only 18.2% achieved the more stringent 2019 target of <55 mg/dL with ≥50% reduction. 3
Even in a healthcare system dedicated to aggressive lipid management, only 43.4% of very high-risk CAD patients achieved LDL-C <70 mg/dL. 7
Approximately 34% of patients fail to reach LDL-C goals despite high-intensity statin treatment, indicating the need for combination therapy with non-statin agents. 3
The percentage reduction from baseline is as important as the absolute LDL-C level achieved. 5
Patients achieving ≥50% LDL-C reduction had better outcomes than those simply reaching <70 mg/dL without adequate percentage reduction. 5
Both criteria (absolute level <70 mg/dL AND ≥50% reduction) should be met when possible. 2
Factors independently associated with failure to attain LDL-C <70 mg/dL include age <65 years, female sex, not receiving statin therapy, and history of creatine kinase elevation. 7