Rate Control Therapy Evaluation in Permanent Atrial Fibrillation (RATE-AF). Presented at the ESC Congress 2020 on 30th August 2020.

Digoxin should be considered first-line therapy for rate control in elderly patients with atrial fibrillation according to the RATE-AF trial presented by Dipak Kotecha, a professor of cardiology at the University of Birmingham at the virtual European Society of Cardiology (ESC) Congress 2020. The open-label trial compared treatment with low-dose digoxin or beta-blocker bisoprolol in 160 elderly patients with permanent atrial fibrillation and breathlessness. The mean age of patients was 76 years, approximately half of them were women, and they were functionally in New York Heart Association (NYHA) class 2 or higher. The primary endpoint was the patient-reported quality of life at six months as measured by the physical component of the Short Form-36 (SF-36) questionnaire, which includes questions regarding perceived limitations for activities of daily living.

Digoxin clearly outperformed bisoprolol in this setting. More than 50% of patients on digoxin improved more than two classes in the modified European Heart Rhythm Association (EHRA) symptom score compared to less than 10% on bisoprolol at six months. At 12 months, approximately 70% of the digoxin group improved by two classes compared with 30% in the bisoprolol group. Improvement in NYHA class and NTproBNP level (a marker of heart failure) over 6 to 12 months was significantly higher in the digoxin group. There was also lower all-cause mortality, cardiovascular mortality and fewer adverse events in the digoxin group, although this didn’t reach statistical significance. Digoxin and bisoprolol proved similarly effective at reducing heart rate, from about 100 bpm at baseline to 70-80 bpm at 6 and 12 months. Both drugs were also well tolerated, with 96% and 89% of patients in the digoxin and bisoprolol group, respectively, still receiving the drug at six months.

Should digoxin become the first-line medication for patients with permanent atrial fibrillation?

It certainly should be considered in elderly sedentary patients, but the results of this trial may not apply to younger, more active patients with faster heart rates where digoxin may not be sufficient. The open-label, un-blinded nature of the trial, no placebo or calcium channel blocker control arm, modest sample size and subjectively reported outcomes would also raise questions about the validity and applicability of the results. Nonetheless, the trial at least partially fills a largely evidence-free zone regarding two established drugs and a prevalent medical condition in the elderly. There is a lot of attention to paroxysmal and persistent atrial fibrillation more common in younger people because they can be treated with catheter ablation, which requires expensive equipment generating sales and attracting research funding. Digoxin is an old drug - in fact, one of the oldest in medicine - and there is no money to be made from studying it. But perhaps, sometimes in old, you find gold.