Quality of life not significantly improved in AF, symptomatic HF with digoxin, bisoprolol
At 6 months, quality of life in patients with permanent atrial fibrillation and symptomatic HF treated with digoxin was not significantly different vs. those treated with bisoprolol, researchers reported.
According to research published in JAMA, although symptom control for AF and symptomatic HF was better among patients prescribed digoxin, the between-group difference for the primary endpoint of self-reported quality of life at 6 months did not meet statistical significance.
“These findings support basing decisions about treatment on other endpoints,” the researchers wrote.
For this randomized, open-label, blinded endpoint clinical trial, researchers enrolled 160 patients aged 60 years or older (mean age, 76 years; 46% women) with permanent AF, defined as no plan to restore sinus rhythm, and dyspnea classified as NYHA class II or higher. Patients were randomly assigned to digoxin (mean dose, 161 g per day) or bisoprolol (mean dose, 3.2 mg per day) to assess differences in patient-reported quality of life using the SF-36 physical component summary score at 6 months.
Quality of life improvement
“Heart rate control is often the sole treatment for impaired quality of life in the context of permanent AF (when there has been a joint decision by the patient and physician not to pursue attempts at restoring normal sinus rhythm),” the researchers wrote. “Without adequate randomized clinical trials, clinicians have relied on anecdotal experience to guide prescription of heart rate control therapy, often defaulting to beta-blockers in routine practice. Despite the long history of digoxin, nonacute randomized clinical trials are only available in the context of heart failure with sinus rhythm.”
Researchers found no significant difference in SF-36 physical component summary score at 6 months among participants who took digoxin (mean score, 31.9) compared with those on bisoprolol (mean score, 29.7; adjusted mean difference, 1.4; 95% CI, 1.1 to 3.8; P = .28).
“The majority of patients in the trial also had other comorbidities, and discussions from the patient focus groups suggested that the benefit to AF-related symptoms was often offset by enhanced appreciation of these comorbidities (particularly large-joint arthritis), leading to a neutral effect on overall quality of life,” the researchers wrote. “This may explain why no significant between-group difference was identified for the summary quality of life domains and the 6-minute walk distance, which highlights the importance of broad and inclusive management of patients with AF and an integrated management approach.”
Secondary endpoints at 6 and 12 months
At 12 months, patients randomly assigned digoxin had better survey scores for vitality (adjusted mean difference, 3.9; 95% CI, 0.8-7; P = .01), general health (adjusted mean difference, 2.8; 95% CI, 0-5.6; P = .05), physical functioning (adjusted mean difference, 2.8; 95% CI, 0-5.7; P = .05) and role physical (adjusted mean difference, 3.4; 95% CI, 0-6.9; P = .05) compared with those who received bisoprolol.
Improvement in modified European Heart Rhythm Association functional class was greater in the digoxin group, with 53% of patients reporting a class improvement of two at 6 months compared with 9% of the bisoprolol group (adjusted OR = 10.3; 95% CI, 4-26.6; P < .001). The difference was maintained at 12 months (aOR = 5.3; 95% CI, 2.5-11.3; P < .001).
At 12 months, median N-terminal pro-B-type natriuretic peptide level was lower in the digoxin group compared with the bisoprolol group (ratio of geometric means, 0.77; 95% CI, 0.64-0.92; P = .005).
Moreover, treatment with digoxin was associated with lower NYHA class compared with the bisoprolol group, at both 6 months (adjusted mean difference, 0.6; 95% CI, 0.7 to 0.4; P < .001) and 12 months (adjusted mean difference, 0.6; 95% CI, 0.8 to 0.4; P < .001).
Researchers also reported that adverse events were less prevalent among the digoxin group (25%) compared with the in the bisoprolol group (64%; P < .001).
“There was better symptom control with digoxin for both AF and heart failure-related symptoms, which is consistent with a significantly lower NT-proBNP level and number of adverse events,” the researchers wrote. “There was no requirement for pacemakers, no increase in pauses, and no deterioration in LVEF with digoxin therapy. In contrast to short-term randomized clinical trials, there was no statistically significant difference for longer-term heart rate control with digoxin compared with bisoprolol or an alternate beta-blocker.”
In a related editorial, Gregory Curfman, MD, deputy editor for JAMA, wrote: “Low-dose digoxin may be considered a viable alternative to beta-blockers to safely achieve heart rate control in patients with permanent AF. The relatively low dose of digoxin (mean, 161 g/d) proved to be sufficient for heart rate control while avoiding the threat of digoxin toxicity.
“Because this trial was small and open label in design, the results may not markedly change the current clinical practice guidelines for heart rate control in AF,” Curfman wrote. “Still, among patients with permanent AF who do not tolerate beta-blockers or calcium channel blockers, or who do not adequately respond to these drugs, digoxin may be useful to consider as a second-line agent.”