The Use of Midodrine in Patients With Advanced Heart Failure

Abstract

In many patients, the treatment of heart failure (HF) cannot be optimized because of pre‐existing or treatment‐induced hypotension. Midodrine, a peripheral α1‐adrenergic agonist may allow for up‐titration of neurohormonal antagonist therapy leading to improved outcomes. Ten consecutive patients with HF due to systolic dysfunction and symptomatic hypotension interfering with optimal medical therapy were started on midodrine. After a 6‐month follow‐up, a higher percentage of patients were on optimal HF therapy (angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker mg % of optimal dose 20% vs 57.5%; P<.001) (β‐blockers mg % optimal dose 37.5% vs 75%; P<.001) (spironolactone/eplerenone mg % 43.7% vs 95%; P<.001). This led to an improvement in left ventricular ejection fraction (baseline 24±9.4 vs 32.2±9.9; P<.001) and clinical outcomes, with a significant reduction in total hospital admissions (32 vs 12; P=.02) and total hospital days (150 vs 58; P=.02).

Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

“…Similarly, inhalation of the a 1 -AR agonist methoxamine improves exercise performance in patients with significant left ventricular contractile dysfunction (Cabanes et al, 1992). Furthermore, in a small cohort of patients with hypotension due to end stage heart failure, the use of the a 1 -AR agonist midodrine is associated with increased contractile function (Zakir et al, 2009). The authors attributed the benefit to a modest increase in blood pressure that resulted from activation of vascular a 1 -ARs, permitting up-titration of recommended heart failure medications (Zakir et al, 2009).…”

“…Furthermore, in a small cohort of patients with hypotension due to end stage heart failure, the use of the a 1 -AR agonist midodrine is associated with increased contractile function (Zakir et al, 2009). The authors attributed the benefit to a modest increase in blood pressure that resulted from activation of vascular a 1 -ARs, permitting up-titration of recommended heart failure medications (Zakir et al, 2009). However, it is possible that direct activation of cardiac a 1 -ARs contributed to this beneficial effect.…”

“…However, in mice, subpressor doses of an a 1 A-subtype-specific ligand prevent doxorubicin cardiotoxicity (Chan et al, 2008;Dash et al, 2011); in humans, some small trials Cardiac a 1 -Adrenergic Receptors indicate a 1 -ARs agonists might improve function in heart failure (Cabanes et al, 1992;Zakir et al, 2009); and numerous studies identify adaptive hypertrophy with subpressor a 1 -agonist infusion, as reviewed in the section on hypertrophy. These data provide a preliminary proof-of-principle demonstration of the efficacy of a 1 -agonists in heart failure, and justify further study.…”

Midodrine and Pyridostigmine; Novelties in Heart Failure Therapy

“…In a separate observational study, Zakir and colleagues showed that in ten patients with systolic heart failure and symptomatic hypotension interfering with optimizing medical therapy, the use of Midodrine was associated with a significant increase in the percentage of patients on optimal medical therapy. 13 At the end of the study 57.5% of patients were on optimal dose of ACEI/ARB vs 20% initially, 75% compared to 37.5% of patients were on optimal dose beta blocker, and 95% compared to 43.7% of patients were on optimal Spironolactone/Eplerenone therapy. (Figure 1) The use of Midodrine was further associated with an improvement in left ventricular ejection fraction.…”

“…[18][19][20][21][22] Pyridostigmine is a reversible acetylcholine esterase inhibitor, it augments the effect of the parasympathetic system. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] It is currently used in the treatment of myasthenia gravis. 23 Several efforts to study the effect of Pyridostigmine in animal models of heart failure have been made.…”