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Randomized Controlled Trial
. 2025 Sep 1;27(9):euaf200.
doi: 10.1093/europace/euaf200.

Atrial fibrillation and implantable cardioverter-defibrillator in non-ischaemic heart failure with reduced ejection fraction: insights from the DANISH trial

Seiko N Doi  1   2 , Adelina Yafasova  1 , Jens Jakob Thune  3   4 , Jens C Nielsen  5   6 , Niels E Bruun  3   7   8 , Lars Videbæk  9 , Hans Eiskjær  5 , Christian Hassager  1   3 , Jesper H Svendsen  1   3 , Dan E Høfsten  1   3 , Steen Pehrson  1 , Lars Køber  1   3 , Jawad H Butt  1   7   10
Affiliations
Randomized Controlled Trial

Atrial fibrillation and implantable cardioverter-defibrillator in non-ischaemic heart failure with reduced ejection fraction: insights from the DANISH trial

Seiko N Doi et al. Europace. .

Abstract

Aims: Atrial fibrillation (AF) is associated with an increased risk of sudden cardiac death. Therefore, the effect of an implantable cardioverter-defibrillator (ICD) may be greater in patients with AF. We examined the long-term effects of primary prevention ICD implantation vs. usual clinical care according to AF status in DANISH.

Methods and results: Outcomes were analysed according to AF status at baseline (history and/or on enrollment ECG). The primary outcome was all-cause death, and secondary outcomes were cardiovascular and sudden cardiovascular death. Of the 1116 patients with non-ischaemic heart failure with reduced ejection fraction randomized in DANISH, 418 (37.5%) had AF at baseline, of whom 24.2% had paroxysmal AF, 17.0% persistent AF, and 58.9% permanent AF. AF status did not significantly modify the effect of ICD implantation on all-cause death, although there was a suggestion of a greater effect in patients with [hazard ratio (HR) 0.78 (95% CI, 0.59-1.03)] vs. without AF [HR 0.98 (0.75-1.27)] (Pinteraction = 0.15). AF status significantly modified the effect of ICD implantation on cardiovascular death, such that ICD implantation was associated with a lower rate of this outcome in patients with AF [HR 0.67 (0.48-0.94)], but not in those without AF [HR 1.04 (0.76-1.41)] (Pinteraction = 0.04). Although AF status did not significantly modify the effect of ICD implantation on sudden cardiovascular death, there was a suggestion of a greater effect in patients with [HR 0.45 (0.24-0.82)] vs. without AF [HR 0.76 (0.41-1.38)] (Pinteraction = 0.20).

Conclusion: In the DANISH trial, the presence of AF was associated with a greater effect of ICD implantation on cardiovascular death, and although similar trends were observed for all-cause and sudden cardiovascular death, the treatment-by-subgroup interaction was not statistically significant for these outcomes.

Registration: URL: https://www.clinicaltrials.gov; unique identifier: NCT00542945.

Keywords: Atrial fibrillation; Clinical trial; Heart failure; Implantable cardioverter-defibrillator.

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Conflict of interest statement

Conflict of interest: J.H.B. reports advisory board honoraria from AstraZeneca and Bayer, consultant honoraria from AstraZeneca and Bayer, and travel grants from AstraZeneca and Bayer outside the submitted work. J.J.T. reports speaker’s honoraria from AstraZeneca and Bristol Myers Squibb, travel grant from AstraZeneca, and research grant from the Novo Nordisk Foundation, outside the submitted work. N.E.B. reports investigator-initiated grants from Novo Nordisk Foundation, Augustinus Foundation, Kaj Hansen Foundation, and Health Insurance Denmark, outside the submitted work. C.H. reports institutional research grants from Novo Nordisk Foundation, Lundbeck Foundation, and the Danish Heart Foundation, outside the submitted work. J.H.S. declares institutional research grants from Medtronic outside the submitted work and reports advisory board honoraria from Medtronic and Vital Beats. S.P. reports lecture honoraria from Abbott and Bayer outside the submitted work. The remaining authors have no disclosures to report.

Figures

Graphical Abstract
Graphical Abstract
Study flow chart and effect of ICD implantation compared with usual care according to baseline AF status. All hazard ratios are stratified according to centre and cardiac resynchronization therapy implantation (preexisting or planned). AF, atrial fibrillation; CI, confidence interval; DANISH, Danish Study to Assess the Efficacy of Primary Prevention of Implantable Cardioverter Defibrillators in Patients with Non-ischaemic Systolic Heart failure on Mortality; HFrEF, heart failure with reduced ejection fraction; ICD, implantable cardioverter-defibrillator.
Figure 1
Figure 1
Effect of ICD implantation compared with usual care according to the type of AF status at baseline. AF, atrial fibrillation; CI, confidence interval; HR, hazard ratio; ICD, implantable cardioverter-defibrillator. All hazard ratios are stratified according to centre and cardiac resynchronization therapy implantation (preexisting or planned).
Figure 2
Figure 2
Effect of ICD implantation compared with usual care according to age in patients with and without AF at baseline. The figures show the effect of ICD implantation vs. usual care on death from any cause and cardiovascular death according to continuous age in patients with and without AF. Linear regression models were applied, since these yielded the lowest Akaike information criterion score. All hazard ratios are stratified according to centre and cardiac resynchronization therapy implantation (preexisting or planned). A hazard ratio below 1 favours ICD implantation. AF, atrial fibrillation; CI, confidence interval; ICD, implantable cardioverter-defibrillator.
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References

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