In this prospective, multicenter, open-label trial, 212 ACS patients will be randomized 1:1 to either the "PCSK9i early" intensified therapy group (initial addition of PCSK9i to moderate-intensity statin) or the guideline-directed medical therapy group for 6 months. Serial OCT imaging of non-culprit arteries (20-70% stenosis) is performed at baseline and 6 months. The primary endpoint is the absolute change in minimum fibrous cap thickness at 6 months, and secondary endpoints including changes in lumen area, lipid arc, macrophage infiltration, LDL-C reduction, and target LDL-C achievement.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
212
Patients randomized to the "PCSK9i early" intensified therapy group will receive initial treatment with a PCSK9 inhibitor-either evolocumab 140 mg or alirocumab 75 mg, both administered subcutaneously every two weeks with the initial dose given during hospitalization and subsequent doses self-administered at home-or inclisiran sodium 300 mg (equivalent to 284 mg inclisiran), administered by healthcare professionals at baseline and again at the 3-month study visit. All patients will receive moderate-intensity statin, including atorvastatin 20 mg or rosuvastatin 10 mg. The intervention will be initiated during hospitalization for the index ACS event, within 24 hours of randomization, irrespective of baseline LDL-C levels or prior statin use.
Absolute change in the minimum fibrous cap thickness of target lesions
Absolute change in the minimum fibrous cap thickness of target lesions from baseline to 6 months.
Time frame: At 6 months post randomization
Percent change in minimum fibrous cap thickness of target vessels
Percent change in minimum fibrous cap thickness of target vessels from baseline to 6 months.
Time frame: At 6 months post randomization
Absolute change in mean minimum fibrous cap thickness across target vessels
Absolute change in mean minimum fibrous cap thickness across target vessels from baseline to 6 months.
Time frame: At 6 months post randomization
Absolute changes in minimum lumen area of target vessels
Absolute changes in minimum lumen area of target vessels from baseline to 6 months.
Time frame: At 6 months post randomization
Absolute changes in maximum lipid arc of target vessels
Absolute changes in maximum lipid arc of target vessels from baseline to 6 months.
Time frame: At 6 months post randomization
Presence of macrophage infiltration in target vessels
Presence of macrophage infiltration in target vessels from baseline to 6 months.
Time frame: At 6 months post randomization
Proportion of patients with OCT-identified vulnerable plaques
Proportion of patients with OCT-identified vulnerable plaques (defined as FCT \< 75 µm plus at least two of three features: lipid arc \> 180°, MLA \< 3.5 mm², and macrophage infiltration) from baseline to 6 months.
Time frame: At 6 months post randomization
Change in total cholesterol
Change in total cholesterol from baseline to 3 and 6 months.
Time frame: At 3 months and 6 months post randomization
Change in apolipoprotein B
Change in apolipoprotein B from baseline to 3 and 6 months.
Time frame: At 3 months and 6 months post randomization
Change in lipoprotein(a)
Change in lipoprotein(a) from baseline to 3 and 6 months.
Time frame: At 3 months and 6 months post randomization
Change in triglycerides
Change in triglycerides from baseline to 3 and 6 months.
Time frame: At 3 months and 6 months post randomization
Change in very low-density lipoprotein cholesterol
Change in very low-density lipoprotein cholesterol from baseline to 3 and 6 months.
Time frame: At 3 months and 6 months post randomization
Change in low-density lipoprotein cholesterol
Change in low-density lipoprotein cholesterol from baseline to 3 and 6 months.
Time frame: At 3 months and 6 months post randomization
Change in high-density lipoprotein cholesterol
Change in high-density lipoprotein cholesterol from baseline to 3 and 6 months.
Time frame: At 3 months and 6 months post randomization
Proportion of patients achieving predefined LDL-C targets
Proportion of patients achieving predefined LDL-C targets (\< 1.4 mmol/L) from baseline to 3 and 6 months.
Time frame: At 3 months and 6 months post randomization
Adherence to lipid-lowering therapy
Adherence (proportion of days covered) to lipid-lowering therapy (statin, cholesterol absorption inhibitor, and PCSK9i) from baseline to 3 months and 6 months.
Time frame: At 3 months and 6 months post randomization
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