Supplementary Material for: The Impact of Midodrine on Outcomes in Patients with Intradialytic Hypotension

Background: Intradialytic hypotension (IDH) is a frequent complication of hemodialysis, and is associated with significant morbidity and mortality. Off-label use of the alpha-1 andrenergic receptor agonist midodrine to reduce the frequency and severity of IDH is common. However, limited data exist to support this practice. This study sought to examine real-world efficacy of midodrine with respect to relevant clinical and hemodynamic outcomes. Methods: Here, we compared a variety of clinical and hemodynamic outcomes among adult patients who were prescribed midodrine (n = 1,046) and matched controls (n = 2,037), all of whom were receiving in-center hemodialysis treatment at dialysis facilities in the United States (July 2015 – September 2016). Mortality, all-cause hospitalization, cardiovascular hospitalization, and hemodynamic outcomes were considered from the month following the initiation of midodrine (or corresponding month for controls) until censoring for discontinuation of dialysis, transplant, loss to follow-up, or study end (September 30, 2016). Rate outcomes were compared using Poisson models and quantitative outcomes using linear mixed models; all models were adjusted for imbalanced patient characteristics. Results: Compared to non-use, midodrine use was associated with higher rates of death (adjusted incidence rate ratio 1.37, 95% CI 1.15–1.62), all-cause hospitalization (1.31, 1.19–1.43) and cardiovascular hospitalization (1.41, 1.17–1.71). During follow-up, midodrine use tended to be associated with lower pre-dialysis systolic blood pressure (SBP), lower nadir SBP, greater fall in SBP during dialysis, and a greater proportion of treatments affected by IDH. Conclusion: Although residual confounding may have influenced the results, the associations observed here are not consistent with a potent beneficial effect of midodrine with respect to either clinical or hemodynamic outcomes.