Digoxin should be considered as a first-line approach for rate control in patients with permanent atrial fibrillation (AF). This was the conclusion of the RATE-AF (RAte control Therapy Evaluation in permanent Atrial Fibrillation) trial, findings from which were presented on behalf of the study investigators by Dipak Kotecha, (University Hospitals Birmingham, Birmingham, UK), at the ESC 2020 Congress (Virtual, 29 August–1 September).
During his presentation, Kotecha noted that the increase in prevalence of AF is expected to dramatically outpace any rise in population, doubling over the next few decades. This is due to an ageing population and an increasing incidence of AF in older people. “Although we seem to have made good progress for younger patients, the mortality remains stubbornly high in those who are most likely to suffer from AF, older patients,” he commented.
Kotecha added that the vast majority of research has been in patients with paroxysmal and sometimes persistent AF, but commented that permanent AF, where rhythm control is not planned, is the most common group of patients. “In these patients over half have or will develop heart failure”, he said.
“Heart rate control is the mainstay of treatment for these patients, after deciding on stroke prevention therapy, but currently we only have short-term trials assessing the acute heart rate response, leaving the choice of therapy to anecdotal experience and observational data.”
Kotecha noted that beta blockers are commonly used to treat these patients due to the beneficial effects in heart failure with reduced ejection fraction (EF). However, this mortality benefit does not appear to extend to those with AF in double-blind randomised trials.
Data on digoxin, another common treatment option, suffers from extreme prescription bias, Kotecha said, as doctors tend to reserve digoxin for sicker, older patients, with more comorbidities. Currently there are no long-term trials of Digoxin in patients with AF or AF with heart failure, Kotecha noted, adding that RATE-AF trial was designed to answer this “important clinical question”.
A total of 160 patients were enrolled in the study, all of whom were 60 years of age or older with permanent AF and breathlessness (NYHA class II or above) in need of rate control for AF. Exclusion criteria were kept minimal to produce a generalisable cohort, Kotecha said, and avoided any exclusions related to heart failure or ejection fraction, apart from recent decompensation.
The primary outcome was quality of life related to physical function at six months, with key secondary outcomes of heart rate, mEHRA symptom classification and NTproBNP at 6 and 12 months, and other adverse clinical events at 12 months.
Patients were randomised to digoxin or bisoprolol in the beta blocker arm. The patients had a mean age of 76 years, and 46% were women, Kotecha explained, adding that AF symptoms in the majority of patients were moderate (47%) or severe (40%) and half (52%) had signs of heart failure at baseline. The average NTproBNP was 1,057pg/mL, and 19% of patients had LVEF <50%.
Detailing the results, Kotecha noted that the primary outcome of physical component quality of life increased from baseline in both groups with no significant difference between digoxin or beta blockers. “You will note the substantial reduction in quality of life across all of these domains compared to the norm for these patients, and also that over time, quality of life across these different domains continued to improve with digoxin and in several areas, such as physical function, vitality and global health, digoxin was superior to beta blockers by 12 months,” he explained.
AF related symptoms were consistently improved with digoxin, Kotecha added, compared to a “much more mixed picture with beta blockers”. He said: “You can appreciate here the substantial number of patients who received digoxin that reached either no, or mild symptoms”.
In a pre-specified analysis of those with a two class improvement in the mEHRA score, over 50% of patients had a two-class improvement with digoxin at six months, and the different compared to beta blockers remained at the 12 month period.
Heart failure outcomes such as NYHA class were improved with digoxin, Kotecha noted, more so than with beta blockers and NTproBNP reduced overall at each timepoint. In contrast, NTproBNP increased with beta blocker therapy.
Summarising the findings, Kotecha commented: “The RATE-AF trial has demonstrated that digoxin therapy in older patients with permanent AF and symptoms of heart failure has a similar effect as beta blockers on both heart rate and the physical components of quality of life. However, digoxin had a considerably better symptom improvement, a reduction in natriuretic peptides and much lower rates of adverse events, without any compromise of LV function.
“Our results suggest a wider use of digoxin for stable patients with permanent AF, and reiterate the need for randomised controlled trials to advise on treatment decisions.”