despite—or perhaps because of—a very long
history of clinical use, high-quality evidence
regarding the long-term clinical
outcomes with digoxin and related cardiac glycosides
is limited. It took until the late 1990s to complete a
large randomized trial that clarified digoxin’s role in
the treatment of heart failure (HF) (decreased hospitalization,
no effect on mortality) (1). With respect
to atrial fibrillation (AF), digoxin’s other main therapeutic
target, no such randomized outcomes trial
has ever been completed. As a result, the best available
evidence on clinical outcomes with digoxin in
AF patients comes from post-hoc analyses of clinical
trials designed to answer other questions, or from
observational studies.