Background Orthostatic hypotension causes ≈80 000 hospitalizations per year in the United States. Treatments for orthostatic hypotension include fludrocortisone, a mineralocorticoid analog that promotes sodium reabsorption; and midodrine, an α‐1 adrenergic agonist that is a direct vasoconstrictor. Although both medications are used to treat orthostatic hypotension, few studies have compared their relative safety.
Methods and Results We compared incidence rates of hospitalizations for all causes, and for congestive heart failure between users of fludrocortisone and users of midodrine in a retrospective cohort study of Tennessee Medicaid adult enrollees (1995–2009). Adjusted incidence rate ratios were calculated using negative binomial regression models. Subgroup analyses based on history of congestive heart failure were conducted. We studied 1324 patients initiating fludrocortisone and 797 patients initiating midodrine. Compared with fludrocortisone users, midodrine users had higher prevalence of cardiovascular conditions. Incidence rates of all‐cause hospitalizations for fludrocortisone and midodrine users were 1489 and 1330 per 1000 person‐years, respectively (adjusted incidence‐rate ratio 1.20, 95% confidence interval, 1.02–1.40). The respective rates of heart failure–related hospitalization were 76 and 84 per 1000 person‐years (adjusted incidence‐rate ratio: 1.33, 95% confidence interval, 0.79–2.56). Among patients with a history of congestive heart failure, the rates of all‐cause hospitalization for fludrocortisone and midodrine were 2448 and 1820 per 1000 person‐years (adjusted incidence‐rate ratio: 1.42, 95% confidence interval, 1.07–1.90), and the respective rates of heart failure exacerbation–related hospitalizations were 297 and 263 per 1000 person‐years (adjusted incidence‐rate ratio: 1.48, 95% confidence interval, 0.69–3.16).
Conclusions Compared with users of midodrine, users of fludrocortisone had higher rates of all‐cause hospitalizations, especially among patients with congestive heart failure.
What Is New?
This is the first study to evaluate the comparative safety of fludrocortisone and midodrine, 2 drugs commonly used for the treatment of orthostatic hypotension.
Fludrocortisone use was associated with increased risk of all‐cause hospitalizations, particularly among patients with prevalent history of heart failure and orthostatic hypotension.
What Are the Clinical Implications?
Our findings should help inform healthcare providers about safety of fludrocortisone use in patients with orthostatic hypotension.
Our findings could be used to aid healthcare providers to make treatment decisions for patients with orthostatic hypotension.
In patients with heart failure and orthostatic hypotension, fludrocortisone should not be used.