What is the role of Midodrine (Midodrine hydrochloride) in heart failure with reduced ejection fraction (HFrEF)?

From the Guidelines

Midodrine is not routinely recommended for patients with reduced ejection fraction heart failure (HFrEF). While midodrine is an alpha-1 adrenergic agonist that increases blood pressure by causing peripheral vasoconstriction, this mechanism can be problematic in HFrEF patients. The increased afterload from vasoconstriction may worsen cardiac function by making the heart work harder to pump against greater resistance, potentially decreasing cardiac output and exacerbating heart failure symptoms.

Key Considerations

• Standard guideline-directed medical therapy for HFrEF includes medications that reduce afterload (such as ACE inhibitors, ARBs, or ARNI), beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, which have proven mortality benefits 1.
• If a patient with HFrEF has symptomatic hypotension limiting optimal heart failure therapy, other strategies should be considered first, such as adjusting diuretic doses, addressing volume status, or temporarily reducing doses of vasodilating medications.
• In specific cases where orthostatic hypotension severely limits quality of life or prevents uptitration of guideline-directed therapy, midodrine might be considered at low doses (2.5-10 mg three times daily) with careful monitoring, but only after consultation with a heart failure specialist 1.

Important Precautions

• The medication should be avoided in patients with severe coronary artery disease, uncontrolled hypertension, or urinary retention.
• The last dose should be taken at least 4 hours before bedtime to avoid supine hypertension.

Guideline Recommendations

• The 2022 AHA/ACC/HFSA guideline for the management of heart failure recommends guideline-directed medical therapy (GDMT) for HFrEF, which includes four medication classes: ACE inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors 1.
• The 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure recommend an ACE-I, a beta-blocker, and an MRA for symptomatic patients with HFrEF to reduce the risk of HF hospitalization and death 1.

From the Research

Role of Midodrine in Heart Failure with Reduced Ejection Fraction (HFrEF)

• Midodrine, an alpha adrenergic agonist, may serve as bridge therapy for the initiation or continuation of Guideline-Directed Medical Therapy (GDMT) in patients with HFrEF and refractory hypotension 2, 3.
• The use of midodrine in patients with HFrEF and symptomatic hypotension may allow for optimization of medical therapy, leading to improved outcomes 4.
• Midodrine may be used off-label in patients with HFrEF and symptomatic hypotension to enable the up-titration of neurohormonal antagonist therapy 3, 4.

Safety and Efficacy of Midodrine in HFrEF

• A retrospective cohort study found that midodrine use was associated with reduced emergency room visits, but increased risks of respiratory failure, intensive care unit admissions, hospitalizations, and mortality in patients with HFrEF 5.
• Another study found that inpatient use of midodrine in patients with heart failure and kidney failure on maintenance dialysis was associated with increased 6-month mortality 6.
• The safety and efficacy of midodrine in HFrEF patients require further investigation, considering the potential risks and benefits of its use 5, 6.

Clinical Implications

• Midodrine may be considered as a treatment option for patients with HFrEF and symptomatic hypotension, but its use should be carefully evaluated and monitored due to potential risks 2, 3, 4.
• The decision to use midodrine in patients with HFrEF should be based on individual patient characteristics, medical history, and clinical judgment, taking into account the potential benefits and risks 5, 6.