Age, frailty of AF patients may account for increased mortality with digoxin
MedWire News: Digoxin use in atrial fibrillation (AF) patients is associated with increased mortality because it is given to an elderly and frail subset of patients, report researchers.
When differences in patient characteristics were accounted for, their study of AF patients enrolled in the Stockholm Cohort Study on AF (SCAF) found no difference in mortality and major cardiovascular events between patients who received digoxin and those who did not.
Previously, randomized data from the Digitalis Investigation Group and the AFFIRM trial found conflicting evidence on the association of digitalis medication with mortality, while the recent RIKS-HIA (Registry of Information and Knowledge about Swedish Heart Intensive care Admissions) showed that intensive care patients with AF but without heart failure had significantly higher mortality if treated with digoxin.
To investigate further, Leif Friberg and colleagues from the Karolinska Institute in Stockholm, Sweden, followed-up 2824 patients with AF for a mean of 4.6 years, using local and national registries to collect information on medication use and diagnoses, hospitalizations, and deaths.
They report that 802 (28%) patients were prescribed digoxin during the study inclusion year, and that these patients differed in important aspects from those who did not receive digoxin.
“In short, a typical recipient of digoxin was an elderly woman with permanent AF, with heart failure, and of generally poorer health than those who did not take digoxin,” they write in an advance online publication by the journal Heart.
In multivariable analysis, permanent AF was the strongest of nine independent determinants of digoxin prescription (hazard ratio (HR)=3.21), followed by absence of a pacemaker (R=2.27), history of heart failure (HR=2.04), and discharge from an internal medicine rather than cardiology ward (HR=1.63). Warfarin use, female gender, chronic pulmonary disease, age older than 80 years, and absence of hypertension were also independently associated with digoxin use.
A total of 1038 patients died during the observation period, of whom 412 received digoxin at index and 626 did not. Mortality was higher in those who received digoxin (51% vs 31%, p<0.0001).
After adjusting for age, gender, comorbidities, and medications, the difference was markedly reduced, however, with a nonsignificant HR of 1.10 for digoxin versus no digoxin.
Further analysis comparing digoxin use at the latest contact during observation confirmed these findings. Similarly, when patients were matched according to individual propensity scores, there was no difference in overall mortality related to digoxin use (HR=1.05).
“Thus, crude differences in mortality appear to be due to patient selection rather than to a deleterious effect of digoxin itself,” write Friberg and team.
The authors also report that there was no disadvantage related to digoxin use in terms of myocardial infarction, ischemic stroke, time to readmission to hospital, or days at hospital per year at risk, although pacemaker implantations were more common in digoxin-treated patients (HR=2.0).
“Digoxin treatment in AF patients appears to be neutral in relation to long-term mortality and major cardiovascular events when age, comorbidity, and other patients characteristics are accounted for,” the team concludes.
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By Caroline Price