From the Guidelines
Midodrine should be used cautiously in heart failure with reduced ejection fraction (HFrEF) patients primarily to manage hypotension that limits the use of guideline-directed medical therapy (GDMT), as evidenced by the importance of optimizing GDMT to reduce morbidity and mortality in HFrEF patients 1. The goal of using midodrine in HFrEF patients is to facilitate the use of GDMT, which includes beta-blockers, renin-angiotensin-aldosterone system (RAAS) agents, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose co-transporter 2 (SGLT2) inhibitors, as these medications have been shown to significantly improve outcomes in HFrEF patients 1. Key considerations for the use of midodrine in HFrEF patients include:
- Starting with a low dose, typically 2.5-5 mg orally three times daily, to minimize the risk of adverse effects
- Avoiding the last dose within 4 hours of bedtime to prevent supine hypertension
- Regularly monitoring blood pressure and assessing for potential side effects, including supine hypertension, urinary retention, and worsening heart failure symptoms
- Limiting the duration of midodrine treatment to the shortest period necessary, with regular reassessment of the need for continued therapy as the patient's condition stabilizes and tolerance to GDMT improves. It is essential to weigh the potential benefits of midodrine against the risks, particularly the risk of increased afterload, which could potentially worsen cardiac function in HFrEF patients 1. Overall, the use of midodrine in HFrEF patients should be guided by the principle of optimizing GDMT to improve morbidity, mortality, and quality of life outcomes, while minimizing the risks associated with midodrine therapy 1.
From the Research
Best Use of Midodrine in HFrEF Patients
- Midodrine can be used as a bridge therapy to initiate or continue Guideline-Directed Medical Therapy (GDMT) in patients with HFrEF and refractory hypotension, as seen in cases where midodrine titration led to marked clinical improvement 2.
- The use of midodrine in patients with advanced heart failure due to systolic dysfunction and symptomatic hypotension can allow for up-titration of neurohormonal antagonist therapy, leading to improved outcomes, including increased left ventricular ejection fraction and reduced hospital admissions 3.
- In patients with HFrEF, midodrine can be used to manage symptomatic or severe persistent hypotension, although guidelines recommend first decreasing blood pressure-reducing drugs not indicated in HFrEF and loop diuretic dose in the absence of associated signs of congestion 4.
- Combination therapy of midodrine and droxidopa may contribute to the maintenance of blood pressure and diuretic activity in patients with heart failure with preserved ejection fraction (HFpEF) and refractory hypotension, although further long-term studies are needed to evaluate the safety and efficacy of this combination therapy 5.
- The management of HFrEF involves the use of diuretics, β-blockers, angiotensin receptor-neprilysin inhibitors, angiotensin-converting enzyme inhibitors, and mineralocorticoid receptor antagonists, among other therapies, with midodrine potentially playing a role in managing hypotension in these patients 6.