What are the LDL‑cholesterol, non‑HDL cholesterol, and triglyceride targets after myocardial infarction, and what stepwise pharmacologic regimen (high‑intensity statin, ezetimibe, PCSK9 inhibitor) should be used to achieve them?

Lipid Targets and Treatment Algorithm After Myocardial Infarction

Primary LDL-C Target

All patients after myocardial infarction should achieve LDL-C <55 mg/dL (<1.4 mmol/L) with at least a 50% reduction from baseline. 1, 2 This represents the "very high risk" or "extremely high risk" category for secondary prevention. 1, 2

Secondary Lipid Targets

• Non-HDL cholesterol target: <85 mg/dL (<2.2 mmol/L) when triglycerides are ≥200 mg/dL. 2 Non-HDL-C is calculated as total cholesterol minus HDL-C. 2
• Triglyceride management: Emphasize lifestyle changes if triglycerides >150 mg/dL (1.7 mmol/L) and/or HDL-C <40 mg/dL (1.0 mmol/L). 3

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Stepwise Pharmacologic Treatment Algorithm

Step 1: Initiate High-Intensity Statin Before Hospital Discharge

Start atorvastatin 40–80 mg daily OR rosuvastatin 20–40 mg daily immediately during hospitalization and continue indefinitely. 1, 2 High-intensity statins reduce LDL-C by ≥50% and lower major cardiovascular events by approximately 15% compared to moderate-intensity statins. 1

• Do not use moderate-intensity statins (e.g., atorvastatin 10–20 mg, simvastatin 20–40 mg) as primary therapy post-MI—they provide suboptimal protection. 1
• Do not de-escalate statin intensity during follow-up in patients who tolerate therapy, even when LDL-C reaches very low levels. 1

Step 2: Reassess LDL-C at 4–8 Weeks Post-Discharge

Obtain a lipid panel 4–8 weeks after the index event to guide further intensification. 1

If LDL-C <55 mg/dL on maximally tolerated statin:

• Continue current high-intensity statin monotherapy. 1 Very low LDL-C levels (<25 mg/dL) have no identified safety concerns and demonstrate ongoing cardiovascular benefit. 2

If LDL-C 55–69 mg/dL on maximally tolerated statin:

• Adding ezetimibe 10 mg daily is reasonable (Class IIa recommendation). 1 Ezetimibe provides an additional 15–25% LDL-C reduction by blocking intestinal cholesterol absorption. 1

If LDL-C ≥70 mg/dL on maximally tolerated statin:

• Add ezetimibe 10 mg daily immediately (Class I recommendation, Level A evidence). 1, 2 This combination reduces LDL-C by an additional 15–25% and has proven cardiovascular benefit in the IMPROVE-IT trial, which showed a 7% relative risk reduction in major cardiovascular events over 6 years. 1

Step 3: Further Intensification if LDL-C Remains ≥70 mg/dL Despite Statin + Ezetimibe

Add a PCSK9 inhibitor (evolocumab 140 mg every 2 weeks or 420 mg monthly, OR alirocumab 75–150 mg every 2 weeks) after 4–6 weeks. 1, 2 PCSK9 inhibitors provide an additional 50–60% LDL-C reduction and reduce major adverse cardiovascular events by approximately 15% over 2–3 years. 1, 4

• Patients treated closer to their ACS event derive greater absolute cardiovascular benefit from PCSK9 inhibitors. 1
• The percentage LDL-C reduction with PCSK9 inhibitors is actually greater in patients with lower baseline LDL-C (66.1% reduction at baseline LDL-C 70 mg/dL vs. 59.4% at 130 mg/dL). 5

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Alternative Consideration: Upfront Combination Therapy

Concurrent initiation of ezetimibe 10 mg with high-intensity statin at hospital discharge may be considered (Class IIb recommendation) to accelerate achievement of LDL-C goals in extremely high-risk ACS patients. 1 This novel approach avoids prolonged exposure to elevated LDL-C during the vulnerable early post-ACS phase. 1

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Management of Statin-Intolerant Patients

Non-statin lipid-lowering therapy is mandated (Class I recommendation) for patients who cannot tolerate statins. 1

• Bempedoic acid 180 mg daily emerges as the preferred option, reducing MACE by 13% in statin-intolerant patients with or at high risk for ASCVD. 1
• Bempedoic acid reduces LDL-C by 15–25% through ATP citrate lyase inhibition in the liver. 1
• Monitor for elevated uric acid levels and gout risk with bempedoic acid. 1
• PCSK9 inhibitors are safe and well-tolerated in statin-intolerant patients, though outcome data as monotherapy are limited. 4

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Evidence Supporting Aggressive LDL-C Lowering

• Every 39 mg/dL (1.0 mmol/L) reduction in LDL-C is associated with approximately 22% relative reduction in cardiovascular events over 4–5 years. 1
• The PROVE-IT TIMI 22 trial demonstrated that achieving median LDL-C of 62 mg/dL with atorvastatin 80 mg resulted in 16% reduction in major cardiovascular events compared to achieving 95 mg/dL with pravastatin 40 mg. 2
• Clinical trials show continuous cardiovascular benefit with no lower threshold—patients achieving LDL-C <25 mg/dL demonstrate ongoing risk reduction without safety concerns. 2

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Critical Safety Monitoring

• Check hepatic transaminases and creatine kinase before initiating high-intensity statins or combination therapy. 1 Atorvastatin 80 mg is associated with 3.3% incidence of >3-fold ULN transaminase elevation. 1
• Monitor liver function tests with bempedoic acid. 1
• Myopathy risk remains <0.1% at guideline-recommended statin doses; serious muscle injury is rare. 1
• No safety concerns exist for achieving very low LDL-C concentrations. 1 Genetic conditions with lifelong very low LDL-C demonstrate no adverse effects and reduced cardiovascular risk. 2

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Common Pitfalls and How to Avoid Them

• Do not add non-statin agents before maximizing statin intensity. High-intensity statin therapy should be achieved prior to introducing ezetimibe or PCSK9 inhibitors, except when high-intensity statins are not tolerated. 1
• Do not hesitate to add ezetimibe and PCSK9 inhibitors when targets are not met—only 22% of very high-risk secondary prevention patients in Europe achieve LDL-C <55 mg/dL. 1
• Do not accept suboptimal LDL-C levels. Approximately 20% of ACS patients experience a recurrent cardiovascular event within 24 months, underscoring the need for aggressive early LDL-C lowering. 1
• Initiate lipid-lowering medications before hospital discharge—patients who start statins before discharge are much more likely to be taking them and to have achieved target LDL-C levels than those who are not treated in this manner. 3, 2

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Recent Evidence on Very-High-Intensity vs. High-Intensity Statins

A 2026 pragmatic trial compared very high-intensity statins (atorvastatin 80 mg or rosuvastatin 40 mg) versus high-intensity statins (atorvastatin 40 mg or rosuvastatin 20 mg), both combined with ezetimibe 10 mg, initiated during AMI hospitalization. 6 The primary endpoint (LDL-C <55 mg/dL AND ≥50% reduction) occurred in 63% of very high-intensity patients versus 52% of high-intensity patients (p=0.13). 6 However, very high-intensity regimens had higher rates of intolerance-related dose reduction (8% vs. 2%, p=0.03). 6 This suggests that starting with high-intensity statin plus ezetimibe may be a pragmatic approach, reserving very high-intensity statins for patients who do not achieve targets on the high-intensity regimen. 6