Impact of PCSK9 inhibitors on bleeding and adverse outcomes in post-PCI patients undergoing antiplatelet therapy: A real-world cohort study

Abstract

Background: The relationship between low-density lipoprotein cholesterol (LDL-C) levels and bleeding risk during antiplatelet therapy post-percutaneous coronary intervention (PCI) is uncertain, and the effect of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) on bleeding risk is unknown. Methods: This retrospective cohort study analyzed data from 85,464 PCI patients on oral antiplatelet therapy across 82 Tianjin hospitals from 2017 to 2023, using 1:1 PSM. The primary outcome was Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding within one year. Kaplan-Meier survival curves and Cox regression models were employed to assess the association between PCSK9i and clinical outcomes, with Win-ratio analysis used for composite endpoints. Results: Among 85,464 patients (64 % male), 1979 (2.32 %) received PCSK9i were followed for one year. After PSM, a balanced cohort of 1951 patients in both the PCSK9i and control groups was established. Multivariate cox regression analysis revealed that patients on PCSK9i had significantly reduced risks of NACE (aHR: 0.674, 95 %CI: 0.528-0.859, P = 0.001), MACCE (aHR: 0.674, 95 %CI: 0.524-0.866, P = 0.002), all-cause death (aHR: 0.501, 95 %CI: 0.275-0.915, P = 0.025), and revascularization (aHR: 0.604, 95 %CI: 0.419-0.872, P = 0.007) at one year. No significant differences were found in other endpoints. The hierarchical outcome significantly favored PCSK9i (matched win ratio 0.634, 95 % CI: 0.584-0.689, P < 0.001). Conclusions: PCSK9i therapy did not increase bleeding risk and was associated with lower risks of adverse outcomes compared to the control group.