Digoxin Topic Review

Digoxin, originally derived from the foxglove flower, blocks the sodium/potassium ATPase pump. The mechanism by which this decreases atrioventricular (AV) conduction is not clear, butperhaps it is due to increased vagal tone.

Intracellular calcium within the cardiac myocytes is increased by digoxin, due to calcium channels opening, allowing calcium influx, resulting in increased inotropy (contractility). Thus, digoxin is frequently used when atrial fibrillation (AF) and left ventricular systolic dysfunction coexist. Digoxin toxicity is a concern and is discussed elsewhere (see Digoxin Toxicity).

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Digoxin causes a characteristic appearance on the ECG with “reverse check mark” sign, even in the absence of toxicity.

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Digoxin is effective to reduce ventricular rates at rest. However, it is not effective during physical activity and thus it is recommended to use digoxin in combination with a beta-blocker or non-dihydropyridine calcium channel blocker.

Digoxin therapy gets a class 2b indication for the treatment of symptomatic systolic congestive heart failure (HF); it might be considered to reduce HF hospitalization in patients who remain symptomatic despite guideline-directed medical therapy, or who cannot tolerate guideline-directed medical therapy. [Heidenreich PA, et al. J Am Coll Cardiol. 2022;e316] The DIG (Digitalis Intervention Group) trial showed no mortality benefit, but did indicate improvement in symptoms and fewer hospitalizations for HF. A subanalysis showed that keeping levels between 0.5 and 1 ng/mL in men and 0.5 and 0.8 ng/mL in women reduces the risk for toxicity while maintaining clinical benefit.

Commonly, if systolic HF is present in combination with AF and an uncontrolled ventricular rate, digoxin therapy is utilized.

Digoxin is only used in diastolic HF if AF is present with uncontrolled ventricular rates.

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As a Class V antiarrhythmic drug, digoxin has a class 2a indication for acute rate control in AF for patients who cannot take a beta-blocker or non-dihydropyridine calcium channel blocker, and for long-term rate control in conjunction with a beta-blocker or non-dihydropyridine calcium channel blocker or as monotherapy if those are contraindicated or not tolerated. [Joglar JA, et al. J Am Coll Cardiol. 2023;67,70]. Digoxin also has a class 2a indication to control heart rate in patients with AF and HF in combination with other agents or as monotherapy if those are contraindicated or not tolerated. [Joglar JA, et al. J Am Coll Cardiol. 2023;102]

Digoxin has a class 3 indication (may be harmful) for use in patients with preexcited AF due to risk for precipitating ventricular fibrillation or hemodynamic deterioration. [Joglar JA, et al. J Am Coll Cardiol. 2023;111]

Digoxin, either alone or in combination with beta-blockers, is reasonable (class 2a recommendation) to use for rate control in pregnant patients with persistent AF. [Joglar JA, et al. J Am Coll Cardiol. 2023;120].

References:

• Gheorghiade M, et al. Circulation. 2006;doi:10.1161/CIRCULATIONAHA.105.560110.

• Heidenreich PA, et al. J Am Coll Cardiol. 2022;doi:10.1016/j.jacc.2021.12.012.

• Joglar JA, et al. J Am Coll Cardiol. 2023;doi:10.1016/j.jacc.2023.08.017.