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

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