Renin–angiotensin–aldosterone system inhibition and haemocompatibility-related adverse events in patients with durable left ventricular assist device: the MOMENTUM-3 trial

BACKGROUND AND AIMS: Hemocompatibility-related adverse events (HRAE), particularly mucosal bleeding, remain a limitation of durable left ventricular assist device (LVAD) therapy despite engineering advances. Persistent neurohormonal activation during continuous-flow support may contribute to vascular maladaptation and bleeding vulnerability. This study evaluated whether renin-angiotensin-aldosterone system inhibition (RAASi) is associated with reduced hemocompatibility burden in a large contemporary LVAD cohort. METHODS: This is a secondary analysis of 1,855 clinically stable recipients of a fully magnetically levitated LVAD enrolled in the MOMENTUM-3 trial portfolio. RAASi exposure was defined at landmark 1-month following implantation. Adjusted rate ratios (aRR) for two-year HRAEs were estimated using multivariable Poisson models, complemented by propensity matching and sustained-exposure sensitivity analyses. RESULTS: RAASi therapy at one month was associated with lower rates of composite HRAEs at two years (aRR 0.83, 95% CI 0.75-0.91; p=0.0001), driven predominantly by reductions in non-surgical bleeding (aRR 0.82, 95% CI 0.73-0.90; p=0.0001). Associations remained consistent after propensity matching and were more pronounced among patients with sustained exposure (aRR 0.67, 95% CI 0.56-0.80; p<0.0001). Similar effects were observed across centrifugal (HM3) or axial (HM II) continuous-flow device platforms and were independent of longitudinal differences in mean arterial pressure or anticoagulation intensity. CONCLUSIONS: In this large clinical trial cohort, RAASi was consistently associated with lower rates of hemocompatibility-related adverse events, driven by reductions in non-surgical bleeding. These findings suggest that pharmacological modulation of neurohormonal pathways may represent a complementary strategy to technological innovation in optimizing long-term outcomes during durable LVAD support.