Achieving an LDL-C level ≤ 0.78 mmol/L in ACS patients on PCSK9 inhibitors and DAPT did not significantly increase the risk of clinically relevant bleeding compared to higher LDL-C levels (6.7% vs 5.0%, p=0.72).
Cohort (n=120)
Open-label
No
Does achieving an LDL-C level ≤0.78 mmol/L increase bleeding risk or alter coagulability in post-PCI ACS patients receiving PCSK9 inhibitors and DAPT?
Achieving ultra-low LDL-C levels (≤0.78 mmol/L) with PCSK9 inhibitors in post-PCI ACS patients on DAPT does not appear to increase bleeding risk or alter platelet reactivity, supporting the safety of profound lipid-lowering.
Effect estimate: Risk difference 1.7% (95% CI -6.7% to 10.0%)
Absolute Event Rate: 6.7% vs 5%
Absolute Risk Reduction: -1.7%
p-value: p=0.72
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 ( n = 7), the pre-specified non-inferiority analysis was severely underpowered; therefore, these safety findings are reported descriptively. Exploratory time-to-event analysis showed no significant difference in overall bleeding risk (log-rank P = 0.72). Global coagulability and specific platelet reactivity parameters remained stable throughout follow-up, with no significant intergroup differences (all P 0.05). Major adverse cardiovascular events (MACE) occurred in 6.7% of the Low LDL-C group and 13.3% of the Non-Low LDL-C group (HR 0.48, 95% CI: 0.15–1.55; log-rank P = 0.22). 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.
Fu et al. (Wed,) conducted a cohort in Acute coronary syndrome (ACS) post-PCI (n=120). Achieved Low LDL-C (≤ 0.78 mmol/L) vs. Non-Low LDL-C (>0.78 mmol/L) was evaluated on Clinically relevant bleeding (BARC types 2, 3, or 5) (Risk difference 1.7%, 95% CI -6.7% to 10.0%, p=0.72). Achieving an LDL-C level ≤ 0.78 mmol/L in ACS patients on PCSK9 inhibitors and DAPT did not significantly increase the risk of clinically relevant bleeding compared to higher LDL-C levels (6.7% vs 5.0%, p=0.72).