UPPSALA, SWEDEN. A subgroup analysis of data from the large AFFIRM trial (rate control vs. rhythm control) found that digoxin use was associated with a 42% increase in mortality. At the time, this finding was dismissed as likely being due to the drug being prescribed for patients at greater risk of death such as those with congestive heart failure (CHF). A group of researchers from Uppsala University now demolishes this myth and, as an aside, points out that, although digoxin has been routinely prescribed for atrial fibrillation (AF) patients for close to 100 years, its long-term safety has never been evaluated in this patient population.

The Uppsala study involved 60,764 patients admitted to 73 coronary care units in Sweden during the period 1995 to 2003. Of these, 21,459 were admitted with AF, 22,345 with CHF, and 16,960 with both AF and CHF. About 27% of the patients were discharged with a prescription for digoxin. Among those with only AF (no CHF) 23% were discharged on digoxin. The Swedish investigators monitored the death rate among the various patient groups and found that there was no difference in mortality (27.3%/year) in the AF and CHF group whether or not the patients were on digoxin. In the CHF group, overall mortality was 23.9%/year, but those on digoxin had an 11% higher mortality than those not on digoxin. Finally, in the AF group where overall mortality rate was 9.8%/year, the annual death rate was 42% higher among digoxin users than among those who had not been prescribed digoxin.

All mortality rates were adjusted for about 60 possible confounding variables (other possible risk factors for death). Of particular interest to lone afibbers is the finding that the detrimental effects of digoxin were far worse for relatively healthy patients than for those with multiple risk factors. Thus, AF patients with AF and the least number of other risk factors were more than twice as likely to die within a year after leaving hospital if they had been prescribed digoxin.

The researchers conclude that digoxin is an independent risk factor for death among AF patients placed on long-term therapy with the drug. They also point out that there is no evidence that digoxin is helpful in speeding up conversion to normal sinus rhythm, or in preventing recurrence of AF episodes.

Hallberg, P, et al. Digoxin and mortality in atrial fibrillation: a prospective cohort study. European Journal of Clinical Pharmacology, Vol. 63, 2007, pp. 959-71

Editor's comment: In my first book I described digoxin as truly "the medicine from hell" and recommended that it never be used by lone afibbers. My conclusion was based on research that showed digoxin actually promoted the occurrence of afib episodes, prolonged their duration, and hastened the progression of paroxysmal AF to permanent. As if this was not enough, digoxin has also been found to cause visual problems and to aggravate asthma. Because the "therapeutic window" for digoxin is very narrow, toxic reactions are common and it is estimated that about 6% of all users end up in hospital with a severe case of digoxin intoxication. This latest finding that digoxin use doubles the death rate among relatively healthy afibbers will, hopefully, convince readers of "The AFIB Report" to never accept a prescription for digoxin. As a matter of fact, if your GP or cardiologist recommends its use, it is high time to find another doctor.