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Digoxin improves symptoms in stable patients with permanent AF

Presented by
Prof. Dipak Kotecha, University of Birmingham, UK
ERS 2020
Phase 4, RATE-AF trial
The RATE-AF trial showed a similar effect of low-dose digoxin on both heart rate and the physical component of quality of life compared with beta-blockers [1]. Yet, digoxin-treated patients showed significantly better symptom improvement, a reduction in natriuretic peptides, and substantially less adverse events without compromising left ventricular function. These results suggest that digoxin could be considered as a first-line approach for rate control in stable patients with permanent atrial fibrillation (AF).

Beta-blockers are commonly used for rate control due to their beneficial effects in heart failure with reduced ejection fraction. However, the observed mortality benefit does not appear to extend to those with AF in double-blind, randomised trials. Data on digoxin suffers from prescription bias, as doctors typically preserve digoxin for sicker, older patients with more comorbidities. Although digoxin has been in use since 1785, no longer-term trials with digoxin in patients with AF or AF with heart failure have been performed.

This was the motivation for the randomised, phase 4 RATE-AF trial to evaluate beta-blockers and digoxin for long-term heart rate control in patients with permanent AF and symptoms of heart failure. The trial, presented by Prof. Dipak Kotecha (University of Birmingham, UK), included 160 patients in need of rate control for AF, aged ≥60 years (mean age 76 years), and with permanent AF and breathlessness (NYHA class II or above). Most AF symptoms at baseline were moderate or severe: modified EHRA 2b was present in 47% of patients and mEHRA 3 in 40%. Over half (52%) had signs of heart failure at baseline (median NTproBNP 1,057 pg/mL; 19% had a LVEF <50%).

The results showed that heart rate reduced at a similar extent in patients who received a beta-blocker or digoxin. The primary outcome, SF36 quality of life using the Physical Component Summary score at 6 months, increased in both groups with no significant difference (adjusted mean difference 1.33; 95% CI -1.22-3.89; P=0.30; see Figure). Notably, the participants showed a substantial lower quality of life across all domains compared with the norm for these patients. Over time, quality of life across these domains continued to improve with digoxin.

Figure: Patient-reported quality of life in the RATE-AF trial [1]

  1. Kotecha D. RAte control Therapy Evaluation in permanent Atrial Fibrillation. Atrial Fibrillation session, ESC Congress 2020, 29 Aug.

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