Outcomes of Early Sodium-Glucose Cotransporter 2 Inhibitor Use in Takotsubo Syndrome: Insights from a Multicenter Real-World Cohort Study

Pharmacologic management after Takotsubo syndrome (TTS) remains empirical. We evaluated whether early sodium-glucose cotransporter-2 inhibitor initiation after TTS was associated with clinical outcomes in a large real-world cohort. Using the TriNetX US Collaborative Network, we identified adults with incident TTS from 2015 to 2025. Patients initiated on a sodium-glucose cotransporter-2 inhibitor within 14 days were propensity-matched 1:1 to patients without early sodium-glucose cotransporter-2 inhibitor use. Follow-up for time-to-event analyses began on day 14. The primary outcome was all-cause mortality. Secondary outcomes were heart failure hospitalization, cardiogenic shock, cardiac arrest, and major adverse cardiovascular events. A total of 54,701 patients with TTS, 1,803 matched pairs were analyzed. Early sodium-glucose cotransporter-2 inhibitor use was associated with lower all-cause mortality (8.1% vs 13.6%; hazard ratio 0.71; 95% confidence interval 0.58 to 0.87; p = 0.001). Associations were not significant for heart failure hospitalization, cardiogenic shock, cardiac arrest, or major adverse cardiovascular events. Mortality findings were directionally consistent in sensitivity analyses excluding patients with COVID-19 and, separately, diabetes mellitus. In this observational landmark analysis, early sodium-glucose cotransporter-2 inhibitor use after TTS was associated with lower all-cause mortality but not lower cardiovascular event rates.