Does digoxin cause more harm than good?

Digoxin is classed as a cardiac glycoside and has been used for hundreds of years for its positive inotropic effects in heart failure (HF) caused by decreased ventricular contractility (Eade et al, 2013). Cardiac glycosides act by inhibiting the enzyme associated with the sodium potassium pump (adenosine triphosphatase) causing intracellular sodium to increase. As a result, the normal exchange of sodium and calcium is impaired, leading to a reduced removal of calcium from the cardiac muscle cell (Galbraith et al, 2007).

Consequently, more calcium is pumped into the sarcoplasmic reticulum (SR) to be stored. When an action potential excites the cell, the abundant calcium is released from the SR to the myofilaments and increases the force of contraction (Lilly, 2016).

Additionally, cardiac glycosides have a negative chronotropic and dromotropic effect, which are desirable in the therapeutic management of HF and/or rate control in atrial fibrillation (AF). By enhancing the parasympathetic stimulation of the heart, cardiac glycosides decrease impulse generation of the sinoatrial (SA) node and therefore reduce conductivity within the atrioventricular (AV) node (Galbraith et al, 2007; Joint Formulary Committee, 2019). As the conduction velocity between the AV node and ventricles decreases, the interval between atrial and ventricular contraction increases, which slows the ventricular rate and allows more time for the ventricles to fill (Galbraith et al, 2007; Lilly, 2016).