Is there a benefit to adding midodrine to a congestive heart failure (CHF) regimen when sacubitril/valsartan (Entresto) is used concurrently?

From the Guidelines

Adding midodrine to a heart failure regimen that includes Entresto (sacubitril/valsartan) may provide benefit in specific clinical scenarios, particularly for patients with persistent hypotension that limits optimal heart failure therapy. Midodrine, an alpha-1 adrenergic agonist, can increase blood pressure by causing peripheral vasoconstriction, which may help counteract the hypotensive effects of Entresto. This combination might be useful when patients cannot tolerate target doses of Entresto or other heart failure medications due to symptomatic low blood pressure. However, this approach requires careful monitoring as midodrine could potentially counteract some of the beneficial vasodilatory effects of Entresto. The typical dosing of midodrine is 2.5-10 mg three times daily during waking hours (avoiding administration before bedtime to prevent supine hypertension) 1. This combination should be used cautiously, with close monitoring of blood pressure, renal function, and heart failure symptoms. The decision to add midodrine should be individualized based on the patient's specific hemodynamic profile, symptom burden, and ability to tolerate guideline-directed heart failure therapies. According to the 2022 AHA/ACC/HFSA guideline for the management of heart failure, patients with heart failure with reduced ejection fraction (HFrEF) should be treated with sacubitril/valsartan to reduce the risk of hospitalization and death 1. However, there is no direct evidence from these guidelines regarding the use of midodrine in combination with Entresto. Therefore, the use of midodrine in this context should be based on the individual patient's needs and clinical judgment. It is essential to weigh the potential benefits of adding midodrine against the potential risks, including supine hypertension and interactions with other medications. Close monitoring and careful dose titration are necessary to minimize adverse effects and optimize the therapeutic benefits of this combination. In patients with chronic heart failure, the use of midodrine has been associated with improved symptoms and exercise capacity, but its effects on morbidity and mortality are not well established 1. In summary, the addition of midodrine to a heart failure regimen that includes Entresto may be considered in specific clinical scenarios, but it requires careful monitoring and individualized decision-making. The patient's response to treatment should be closely monitored, and adjustments to the treatment plan should be made as needed to optimize outcomes and minimize adverse effects. Key considerations include:

• Close monitoring of blood pressure, renal function, and heart failure symptoms
• Individualized decision-making based on the patient's specific hemodynamic profile, symptom burden, and ability to tolerate guideline-directed heart failure therapies
• Careful dose titration to minimize adverse effects and optimize therapeutic benefits
• Consideration of potential interactions with other medications and the risk of supine hypertension.

From the Research

Benefits of Midodrine in CHF Regimen with Entresto

• There is no direct evidence in the provided studies to support the benefit of midodrine being added to a CHF regimen when Entresto is used concurrently 2, 3, 4, 5, 6.
• The studies focus on the benefits and mechanisms of action of sacubitril/valsartan (Entresto) in the treatment of heart failure with reduced ejection fraction (HFrEF) 2, 3, 4, 5.
• One study investigates the effects of metoprolol succinate combined with Entresto on cardiac function and coagulation function in patients with congestive heart failure, but does not mention midodrine 6.
• The provided evidence does not address the specific question of adding midodrine to a CHF regimen with Entresto, and therefore, no conclusion can be drawn from the available data 2, 3, 4, 5, 6.

Entresto Mechanism and Benefits

• Entresto (sacubitril/valsartan) is an angiotensin receptor-neprilysin inhibitor that has been shown to reduce mortality and hospitalization rates in patients with HFrEF 2, 3, 4, 5.
• The mechanism of action of Entresto involves the inhibition of neprilysin and the blockage of angiotensin receptors, leading to improved cardiac function and reduced disease progression 2, 3, 4, 5.
• The studies highlight the importance of Entresto in the treatment of HFrEF and its potential benefits in improving cardiac function, reducing hospitalization rates, and enhancing quality of life 2, 3, 4, 5.