Implantable Cardioverter-Defibrillator Therapy in Contemporary Heart Failure Patients: an Analysis from the EMPEROR-Reduced Trial

Background The benefit of an implantable cardioverter-defibrillator (ICD) in patients with heart failure with reduced ejection fraction on foundational therapy that includes a sodium-glucose cotransporter 2 inhibitor is unknown. Objectives This study aims to evaluate the impact of an ICD among participants enrolled in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction). Methods Propensity score matching was used to compare outcomes in patients with and without an ICD in the placebo and empagliflozin arms of the EMPEROR-Reduced trial. Time-to-event curves and Cox regression analysis were used to evaluate the risk of the primary endpoint of sudden cardiac death (SCD). Results A total of 1,674 patients were included in the analysis of whom 837 (429 on placebo and 408 on empagliflozin) with an ICD at baseline were matched to 837 (424 on placebo and 413 on empagliflozin) without an ICD. Background therapy included an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor blocker-neprilysin inhibitor (≥88%); beta-blockers (≥94%), and mineralocorticoid receptor antagonists (≥65%). Cox regression analysis showed ICD vs non-ICD treatment was associated with a lower risk of SCD in both the empagliflozin (HR: 0.59; 95% CI: 0.26-1.3) and placebo arms of the trial (HR: 0.31; 95% CI: 0.13-0.74), treatment-by-ICD interaction P = 0.30. Conclusions In patients with heart failure with reduced ejection fraction enrolled in EMPEROR-Reduced, those with an ICD (vs non-ICD) experienced a lower risk of SCD regardless of empagliflozin treatment.