Abstract Body: Background:
Midodrine is often used off-label to manage hypotension in patients with heart failure with reduced ejection fraction (HFrEF), but its long-term safety and clinical impact remain unclear. This study evaluated real-world outcomes associated with midodrine use in this population.
Methods:
We conducted a retrospective cohort study using electronic health records from the TriNetX US Collaborative Network. Adults with HFrEF < 40% were divided into two propensity score–matched cohorts: those treated with midodrine (n=107,814) and those without midodrine exposure (n=107,814). Clinical outcomes assessed included all-cause mortality, acute heart failure exacerbations, atrial arrhythmias, acute kidney injury (AKI), and emergency department (ED) visits. Risk differences, incidence rates, and Kaplan-Meier survival analyses were performed.
Results:
Midodrine use was associated with a significantly higher risk of mortality (42.8% vs. 29.8%; risk difference +13.0%, p<0.001) and AKI (37.3% vs. 34.6%; risk difference +2.7%, p<0.001). However, patients receiving midodrine had lower risks of atrial fibrillation/flutter (45.8% vs. 55.7%; risk difference -9.9%, p<0.001), acute systolic heart failure (29.0% vs. 30.3%; risk difference -1.3%, p<0.0001), acute diastolic HF (13.0% vs. 16.0%; risk difference -3.0%, p<0.001), and ED visits (34.9% vs. 41.1%; risk difference -6.2%, p<0.001).
Conclusions:
In this large real-world cohort, midodrine use in patients with heart failure with reduced ejection fraction was associated with increased mortality and a higher risk of acute kidney injury. One possible explanation may lie in the fact that midodrine is a peripheral vasoconstrictor and may counteract the vasodilatory effects of GDMT, potentially undermining its benefits. However, midodrine was also associated with lower rates of atrial arrhythmias, acute heart failure exacerbations, and overall emergency department visits. These findings suggest that while midodrine may carry important risks, it could also reduce symptom burden and healthcare utilization, especially in patients with advanced or end-stage heart failure where improving quality of life and palliative goals are prioritized. Prospective trials are needed to clarify its clinical utility, ideal timing, and patient selection.