Oral Inotropes for Heart Failure
There are essentially no oral inotropes recommended for chronic heart failure treatment, with the sole exception of digoxin, which is the only oral inotropic agent that does not increase mortality. 1, 2
The Critical Evidence Against Oral Inotropes
All oral inotropic agents except digoxin are contraindicated in heart failure due to increased mortality and arrhythmias. The evidence is unequivocal:
Oral milrinone is explicitly contraindicated—FDA labeling warns that long-term oral treatment was associated with no symptom improvement and an increased risk of hospitalization and death in a multicenter trial of 1,088 patients with Class III-IV heart failure 3
Oral enoximone, vesnarinone, and amrinone all invariably increase arrhythmias and mortality in clinical trials (Level A evidence) 4, 1
Oral dopamine analogues (such as ibopamine) are not recommended due to lack of efficacy and safety concerns 4, 1
Digoxin: The Only Acceptable Oral Inotrope
Digoxin is the sole oral inotropic agent that can be used chronically without increasing mortality. 2, 5
Specific Indications for Digoxin
Atrial fibrillation with rapid ventricular rate (>110 bpm) as primary indication 4
Symptomatic heart failure with reduced ejection fraction despite optimal therapy with ACE inhibitors/ARBs, beta-blockers, and diuretics 4
Reduces hospitalizations without affecting mortality in the DIG trial of 6,800 patients with mild-to-moderate heart failure 4, 1
Dosing Considerations
Initial IV dose: 0.25-0.5 mg if not previously used 4
Renal dysfunction: 0.0625-0.125 mg may be adequate in moderate-to-severe renal impairment 4
Monitoring required: Serum digoxin levels should guide maintenance dosing, particularly in elderly patients or those with comorbidities affecting metabolism 4
Why Other Oral Inotropes Failed
The mechanism of harm is consistent across all non-digoxin oral inotropes:
Increased ventricular arrhythmias including nonsustained ventricular tachycardia 3
Increased sudden cardiac death particularly in Class IV heart failure patients 3, 6
No survival benefit despite acute hemodynamic improvements 6, 7
Common Clinical Pitfall
Do not confuse intravenous inotropes with oral formulations. While IV dobutamine, milrinone, dopamine, levosimendan, and enoximone have roles in acute decompensated heart failure with hypoperfusion 4, their oral counterparts are contraindicated for chronic use 4, 1. The only exception to this rule is digoxin, which can be given both IV acutely and orally chronically 4.
Guideline-Directed Medical Therapy Instead
Rather than seeking oral inotropes, optimize evidence-based therapies that actually improve survival: