Association of achieved LDL-C levels with global coagulability and clinical outcomes in patients with acute coronary syndrome receiving PCSK9 inhibitors: a prospective cohort study.

Background: The safety of achieving ultra-low low-density lipoprotein cholesterol (LDL-C) levels in acute coronary syndrome (ACS) patients on dual antiplatelet therapy (DAPT), particularly regarding global coagulability, specific platelet reactivity, and bleeding risk, requires further validation. Methods: In this prospective, open-label, single-center cohort study, 120 post-PCI ACS patients treated with PCSK9 inhibitors and DAPT were enrolled. After a 2-week run-in, patients were stratified by their achieved LDL-C levels into a Low LDL-C group (≤0.78 mmol/L) and a Non-Low LDL-C group (>0.78 mmol/L). Global coagulability and specific platelet reactivity were serially assessed via thromboelastography and rapid platelet function assays over 12 months. The primary safety endpoint was clinically relevant bleeding [Bleeding Academic Research Consortium (BARC) types 2, 3, or 5]. Results: The incidence of clinically relevant bleeding was comparable between the Low LDL-C (6.7%) and Non-Low LDL-C (5.0%) groups (risk difference 1.7%, 95% CI: -5.8% to 9.2%). Due to the sparse number of overall bleeding events ( Conclusion: In ACS patients receiving PCSK9 inhibitors and DAPT, achieving an LDL-C level ≤0.78 mmol/L was associated with neither an increased bleeding risk nor significant alterations in global coagulability and specific platelet reactivity. These exploratory observational findings descriptively support the clinical safety of profound lipid-lowering in this high-risk population.