C27-21 Association of Pcsk9 Inhibitors With Improved Survival in Covid-19: A Multicenter, Propensity-Matched Cohort Study Using Real-World Data

Rationale In COVID-19, the intensity of inflammation and immune activation is closely associated with adverse clinical outcomes. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) plays a central role in low-density lipoprotein receptor homeostasis and may exert effects beyond lipid lowering, including modulation of inflammatory pathways. However, real-world evidence on the association between PCSK9 inhibitor use and clinical outcomes in patients with COVID-19 remains limited. Methods We conducted a multicenter retrospective study using the TrinetX database network, a federated Electronic Medical Record Network including nonpregnant adults hospitalized with COVID-19 pneumonia. Patients were divided into two cohorts depending on PCSK9 inhibitor exposure within one month of admission including Evolocumab, Alirocumab and Inclisiran. 1:1 propensity score matching (PSM) was done to adjust for patient demographics, comorbidities and medications used. The primary outcome was 30-day all-cause mortality. Secondary outcomes included respiratory support requirements (need for invasive mechanical ventilation, continuous positive airway pressure, high-flow nasal cannula support, or endotracheal intubation) and interleukin-6 (IL-6) levels. All statistical analysis was performed on the TrinetX platform. Results Of 176,579 patients who met the inclusion criteria, 451 had exposure to PCSK9 inhibitors within one month of admission. Following PSM, 447 patients were included in each cohort. The 30-day all-cause mortality rate was significantly lower among patients with PCSK9 inhibitor exposure [7.40% (n = 33) vs. 15.50% (n = 69); Risk Ratio = 0.478, 95% CI (0.323, 0.709)]. Survivalanalysis demonstrated a significant benefit for the PCSK9 group (Log-rank p < 0.001), with an observed hazard ratio of 0.457 [95% CI (0.302, 0.692)]. No significant differences were observed in respiratory support requirements or IL-6 levels between the two cohorts. Conclusion In this real-world analysis, prior use of PCSK9 inhibitors was associated with a significant reduction in 30-day all-cause mortality among patients hospitalized with COVID-19 pneumonia. These findings support that PCSK9 inhibition may show a protective benefit in the setting of severe viral infection. However, the lack of significant differences in IL-6 levels suggests that this survival benefit may not be driven by systemic anti-inflammatory effects. Further randomized controlled trials are needed to determine the therapeutic potential of PCSK9 inhibitors in the management of COVID-19 and its underlying mechanisms.