Sex Differences in Vasopressor De-escalation With Arginine Vasopressin in Mixed Cardiogenic-Vasodilatory Shock Under...

Women with cardiogenic shock (CS) under VA-ECMO face excess mortality, yet the pharmacological basis of this disparity remains poorly understood. Arginine vasopressin (AVP) is increasingly used as a non-adrenergic vasopressor in this setting, but whether sex modifies the hemodynamic response to AVP is unknown.

In this multicenter retrospective cohort of VA-ECMO-supported CS patients, we assessed whether sex was independently associated with successful vasopressor de-escalation at 48 hours (norepinephrine equivalent dose [NEE] <0.25 µg/kg/min) after AVP initiation. Multivariable logistic regression and linear mixed-effects models were used to evaluate sex differences in treatment response and NEE trajectories over time.

Among 193 eligible patients, 32% of women achieved successful de-escalation versus 49% of men (p = 0.023). Male sex was independently associated with treatment success (aOR 2.08, 95% CI 1.07-4.15, p = 0.033). A significant sex-by-time interaction was observed in NEE trajectories (p = 0.041), with divergence emerging at 48 hours (NEE 0.24 vs. 0.01 µg/kg/min, p = 0.008). The excess failure risk was confined to postmenopausal women aged ≥55 years (aOR 2.75, 95% CI 1.32-5.93, p = 0.008).

Female sex, particularly in a postmenopausal context, was independently associated with impaired vasopressor de-escalation following AVP in CS on VA-ECMO. These hypothesis-generating findings suggest that hormonal status may modulate vascular responsiveness to AVP and support the need for prospective studies incorporating hormonal profiling.