Renin-angiotensin-aldosterone system inhibition and haemocompatibility-related adverse events in patients with...

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.

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.

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.

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.