Introduction & Objective: We investigated the effect of FXI on mortality in a cohort at increased risk for cardiac death, with a specific focus on risk-modification in case of type 2 diabetes (T2D) or current heart failure.
Methods: The prospective LURIC study recruited 3063 persons undergoing coronary diagnostics. Mortality risk was assessed using Cox proportional hazards models employing restricted cubic splines adjusted for age, sex, BMI and coronary artery disease, with interaction terms between FXI activity and T2D status as well as between FXI activity and brain natriuretic peptide (NTproBNP).
Results: In the unadjusted model, FXI activity demonstrated a U-shaped association with mortality risk (p=0.025): It was protective between 89-139%, but the risk increased at levels outside this range. A significant interaction of FXI activity with T2D (p=0.036) revealed that higher FXI activity was linked to reduced mortality in people without diabetes. However, this relation was inverted in participants with T2D (Fig. 1). NTproBNP was a further significant modifier of the relationship between FXI activity and mortality (p=0.0085).
Conclusion: T2D and NTproBNP significantly alter FXI activity's effect on mortality, underscoring a multifaceted interplay. Upcoming FXI-targeted therapies should be carefully evaluated in persons with diabetes with regards to their efficacy and safety.
K. Prystupa: None. M. Heni: Research Support; Boehringer-Ingelheim. Advisory Panel; Amryt Pharma Plc. Speaker's Bureau; Amryt Pharma Plc. Advisory Panel; Boehringer-Ingelheim, Boehringer-Ingelheim. Speaker's Bureau; Lilly Diabetes, Novartis AG, Novo Nordisk, Sanofi. S. Hörber: None. A. Peter: None. P. Hellstern: None. M. Kelm: Research Support; Edwards Lifesciences Coroporation, Microvision Medical, B.Braun, IPP Med GmbH - Institut für Pharmakologie u. präventive Medizin GmbH, Mars Scientific Advisory Council (MSAC). Other Relationship; Bayer Inc., Abiomed. Board Member; ESC-European Society of Cardiology, DGIM-Deutsche Geselleschaft für Innere Medizin, DSHF-Deutsche Stiftung für Herzforschung, DGK-Deutsche Gesellschaft für Kardiologie. Other Relationship; Kel Con GmbH, diaplan. H. Yamazaki: Other Relationship; AstraZeneca, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd., Kyorin Pharmaceutical Co. Ltd, Takeda Pharmaceutical Company Limited, Takeda Pharmaceutical Company Limited, Magmitt Pharmaceutical Co. M. Roden: Advisory Panel; Eli Lilly and Company. Research Support; Boehringer-Ingelheim. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; TARGET PharmaSolutions, Inc. Speaker's Bureau; AstraZeneca. R. Wagner: Speaker's Bureau; Sanofi. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk.
