2026 Southeastern Residency Conference

Title: Impact of Midodrine on Optimization of Guideline-Directed Medical Therapy in Patients with Heart Failure with Reduced Ejection Fraction
Authors: Isabelle Perling, Jessica Starr, Nathan Pinner, Alyssa Osmonson, Kenda Germain
Objective: Discuss whether the addition of midodrine in patients with heart failure with reduced ejection fraction (HFrEF) facilitates optimization of Step 1 guideline-directed medical therapy (GDMT)
Self-Assessment Question: True or false, the addition of midodrine for HFrEF patients led to optimization of GDMT compared to those not started on midodrine.
Background: Heart failure is a complex syndrome that results from impairment of ventricular filling or blood ejection from the heart. It is classified by ejection fraction with the most common types being heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction.
Guideline-directed medical therapy (GDMT) for HFrEF includes four step 1 agents: renin-angiotensin system inhibition with an angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or angiotensin receptor-neprilysin inhibitors, beta blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors. These treatments prolong patient life, improve symptoms, and reduce hospitalizations for HFrEF patients. Due to the notable blood pressure lowering effects of many of these agents, some patients cannot tolerate full GDMT.
Midodrine is a peripheral alpha-1 agonist that increases arterial and venous tone resulting in increased BP. It is FDA approved for symptomatic orthostatic hypotension but has been used off-label for vasopressor weaning in the intensive care unit and hemodialysis associated hypotension. Because combining multiple agents of GDMT can lower BP, some clinicians are beginning to use midodrine to counteract hypotension and ensure full optimization of GDMT.
Methods: This is a single center, IRB approved, retrospective chart review in patients with HFrEF and at least one Step 1 GDMT agent(s) on their home medication list. Patients with ≥3 normotensive blood pressure readings, contraindications to GDMT, mixed heart failure, end stage kidney disease, liver failure, and addition of midodrine for vasopressor de-escalation or no prescription fill data post-discharge were excluded. The primary endpoint was optimization of Step 1 GDMT, including addition of further agents or dose increases in current. Secondary outcomes include addition of GDMT, dose increase in current GDMT, reduction of GDMT, dose decreases in current GDMT, 30-day re-admission, mortality within a year, ability to come off midodrine, and improvement in ejection fraction.
Results: 28 patients were analyzed, 14 on midodrine and 14 without midodrine. There was no difference in optimization of Step 1 GDMT between the midodrine and matched control group. 3/14 patients in the midodrine group were optimized on step 1 GDMT compared to 6/14 in the control group (p=0.225). There was a meaningful difference in mortality within a year between the midodrine and control groups, 5/14 and 1/14, respectively (p=0.065).
Conclusion: Midodrine did not result in a difference in optimization of GDMT. Mortality was higher in the midodrine group, emphasizing the need for further studies evaluating the safety of the medication in HFrEF patients.