There is no reason to use loading doses of digoxin to initiate therapy in patients with HF. Although some physicians have advocated using serum levels to guide the selection of the dose of digoxin84, there is little evidence to support such an approach. The radioimmunoassay for digoxin was developed to assist in the evaluation of the toxicity and not the efficacy of the drug85. When used for the treatment of HF, there may be little relationship between serum digoxin concentration and the drug’s therapeutic effects, and data suggest that large doses of digoxin may not be more effective than small doses in the treatment of HF86.
Risks of treatment
Although physicians have traditionally been taught that digitalis produces frequent side effects, the drug (as currently prescribed) is well tolerated by most patients with HF87. The principal adverse reactions occur primarily when digoxin is administered in large doses, but large doses may not be needed to produce clinical benefits. The major side effects include cardiac arrhythmias (e.g., ectopic and re-entrant cardiac rhythms and heart block), gastrointestinal symptoms (e.g., anorexia, nausea, and vomiting), and neurological complaints (e.g., visual disturbances, disorientation, and confusion).
Digitalis toxicity is commonly associated with serum digoxin levels more than 2 ng per mL, but may also occur with lower digoxin levels, especially if hypokalemia, hypomagnesemia, or hypothyroidism co-exist88. The concomitant use of quinidine, verapamil, spironolactone, flecainide, propafenone, or amiodarone can increase serum digoxin levels and may increase the likelihood of digitalis toxicity. The dose of digoxin should be reduced if treatment with these drugs is initiated.
In addition, a low lean body mass and impaired renal function can also elevate serum digoxin levels, which may explain the increased risk of digitalis toxicity in elderly patients.
In addition to these established side effects, there is concern that levels of digoxin that are generally considered to be in the therapeutic range (0.7 to 2 ng per mL) may exert deleterious cardiovascular effects in the long term, even though such levels appear to be well tolerated in the short-term. In one major long-term trial, serum digoxin
84 Hoeschen RJ, Cuddy TE. Dose-response relation between therapeutic levels of serum digoxin and systolic time intervals. Am J Cardiol 1975;35:469-72.
85 Beller GA, Smith TW, Abelmann WH, Haber E, Hood WB, Jr. Digitalis intoxication. A prospective clinical study with serum level correlations. N Engl J Med 1971;284:989-97.
86 Slatton ML, Irani WN, Hall SA, et al. Does digoxin provide additional hemodynamic and autonomic benefit at higher doses in patients with mild to moderate heart failure and normal sinus rhythm? J Am Coll Cardiol 1997;29:1206-13.
87 Steiner JF, Robbins LJ, Hammermeister KE, Roth SC, Hammond WS. Incidence of digoxin toxicity in outpatients. West J Med 1994;161:474-8.
88 Fogelman AM, La Mont JT, Finkelstein S, Rado E, Pearce ML. Fallibility of plasma-digoxin in differentiating toxic from non-toxic patients. Lancet 1971;2:727-9.