Low-density lipoprotein cholesterol lowering after non-ST-elevation myocardial infarction in a treatment-naive patient — case discussion

Abbreviations

Case presentation

A 52-year-old man is admitted with NSTEMI and treated with PCI. He has hypertension and smokes. He has never taken a statin or any other lipid-lowering therapy. His admission LDL-C is 4.1 mmol/L (159 mg/dL). He has no diabetes, no chronic kidney disease, no muscle disease and no family history of premature cardiovascular disease. (Practice case; not a real patient.)

Step 1 — Risk category and goal

Discussion:

• ESC/EAS 2025 Table 3 places documented ASCVD, including previous ACS, in the very high-risk category.^[2]
• ESC/EAS 2019 goal for secondary prevention at very high risk: a reduction of 50% or more from baseline and LDL-C below 1.4 mmol/L (below 55 mg/dL) (Class I, Level A); the 2025 update left the goals unchanged.^[1][2]
• ACC/AHA 2026: he has 1 major ASCVD event (ACS within the past 12 months) and at least 2 high-risk features (PCI, hypertension, current smoking), so he meets its very high-risk definition; ACC/AHA 2026 says high-intensity statin therapy should be initiated to achieve a 50% or greater reduction and a goal of LDL-C below 55 mg/dL (1.4 mmol/L) and non-HDL-C below 85 mg/dL (2.2 mmol/L), and to reduce the risk of ASCVD events (COR 1, LOE A).^[3]
• NHFA/CSANZ 2025, in people with ACS: an initial LDL-C target below 1.4 mmol/L and a reduction of at least 50% from baseline is recommended (consensus recommendation).^[4]

Step 2 — What to start during the admission

Discussion:

• He needs his LDL-C to fall from 4.1 to below 1.4 mmol/L, a reduction of more than 65%.^[1]
• ESC/EAS 2025 Figure 2 gives average reductions of about 50% for a high-intensity statin and about 60% for a high-intensity statin plus ezetimibe; on those averages his LDL-C would be about 2 mmol/L on the statin alone and about 1.6 mmol/L with ezetimibe added.^[2]
• The 2025 ESC/EAS update stresses considerable inter-individual variability in response, which necessitates monitoring after any change.^[2]
• He is treatment-naive and, on those averages, is not expected to reach the goal on a statin alone; for such patients ESC/EAS 2025 says initiating high-intensity statin plus ezetimibe during the index ACS hospitalisation should be considered (Class IIa, Level B).^[2]
• NHFA/CSANZ 2025: before discharge, initiate and continue indefinitely the highest tolerated statin dose, unless contraindicated or completely statin intolerant (strong recommendation, high certainty).^[4]
• Regimen: atorvastatin 80 mg, listed as high intensity in ACC/AHA 2026 Table 6, plus ezetimibe 10 mg once daily, the dose in ACC/AHA 2026 Table 5.^[3]
• Before starting, ESC/EAS 2019 Table 13 advises baseline alanine aminotransferase (ALT) and CK; if baseline CK is above 4 times the upper limit of normal, do not start drug therapy and recheck.^[1]
• His regimen is statin with ezetimibe combination therapy, for which ACC/AHA 2026 Table 25 also advises monitoring hepatic transaminase levels before and after starting.^[3]

Step 3 — Follow-up at 6 weeks

Six weeks after discharge he is taking atorvastatin 80 mg and ezetimibe 10 mg with no muscle symptoms.^[3] His LDL-C is 1.7 mmol/L (66 mg/dL). He has had no further event.

Discussion:

• Timing: ESC/EAS 2019 Table 13 advises lipid testing 8 (±4) weeks after starting treatment and 8 (±4) weeks after each adjustment until the goal is achieved; ACC/AHA 2026 says clinicians should perform a lipid profile 4 to 12 weeks after initiation or dose adjustment, and every 6 to 12 months thereafter, to assess efficacy and adherence (COR 1, LOE A).^[1][3]
• His LDL-C has fallen by about 59% from 4.1 mmol/L, so the reduction part of the goal is met, but 1.7 mmol/L is above 1.4 mmol/L.^[1]

Step 4 — The next agent

Discussion:

• ESC/EAS 2019: for secondary prevention, in patients at very high risk not achieving their goal on a maximum tolerated statin and ezetimibe, a combination with a PCSK9 inhibitor is recommended (Class I, Level A).^[1]
• ACC/AHA 2026: in very high-risk clinical ASCVD on maximally tolerated statin, ezetimibe and/or a PCSK9 mAb should be added to reach LDL-C below 55 mg/dL and non-HDL-C below 85 mg/dL and reduce the risk of ASCVD events (COR 1, LOE A).^[3]
• NHFA/CSANZ 2025, in people with ACS: with a suboptimal LDL-C despite maximally tolerated statin and ezetimibe, give PCSK9 inhibitors (strong recommendation, high certainty).^[4]
• Evidence: in FOURIER, evolocumab (140 mg every 2 weeks or 420 mg monthly) on statin therapy reduced LDL-C by 59% versus placebo at 48 weeks (least-squares mean) and the primary end point from 11.3% to 9.8% (hazard ratio 0.85); in ODYSSEY OUTCOMES, alirocumab after ACS reduced the primary end point from 11.1% to 9.5% (hazard ratio 0.85).^[7][8]
• Dosing: ACC/AHA 2026 Table 5 lists alirocumab 75–150 mg every 2 weeks or 300 mg every 4 weeks, and evolocumab 140 mg every 2 weeks, both subcutaneously.^[3]
• If he could not tolerate or obtain evolocumab or alirocumab, or strongly preferred less frequent dosing, ACC/AHA 2026 says adding inclisiran to reach LDL-C below 55 mg/dL and non-HDL-C below 85 mg/dL is reasonable (COR 2a, LOE B-R).^[3]

Step 5 — Lp(a) and ApoB

Discussion:

• Lp(a): ACC/AHA 2026 recommends measurement at least once in all adults for ASCVD risk assessment (COR 1, LOE B-NR); in clinical ASCVD with elevated Lp(a), if LDL-C and non-HDL-C goals are not achieved on maximally tolerated statin, it recommends adding a PCSK9 mAb with proven cardiovascular benefit to achieve the goals and reduce ASCVD risk (COR 1, LOE B-R).^[3]
• ApoB: once LDL-C and/or non-HDL-C goals are achieved, ACC/AHA 2026 says ApoB measurement is reasonable to guide decisions about further therapeutic intensification in adults on lipid-lowering therapy, particularly those with ASCVD, cardiovascular-kidney-metabolic syndrome, type 2 diabetes and/or elevated triglycerides (COR 2a, LOE B-NR).^[3]

Key learning points

• At very high risk, ESC/EAS 2019 asks for two things at once: a 50% or greater reduction and an absolute LDL-C below 1.4 mmol/L.^[1]
• The 2025 ESC/EAS update says initiating high-intensity statin plus ezetimibe during the index ACS hospitalisation should be considered in patients who were treatment-naive and are not expected to achieve the LDL-C goal with statin therapy alone (Class IIa, Level B).^[2]
• ESC/EAS 2019 (Class I, Level A, very high-risk secondary prevention) and NHFA/CSANZ 2025 (strong recommendation, high certainty, people with ACS) both recommend a PCSK9 inhibitor when LDL-C is not at goal on maximally tolerated statin and ezetimibe; ACC/AHA 2026 says ezetimibe and/or a PCSK9 mAb should be added in very high-risk ASCVD (COR 1, LOE A).^[1][4][3]