Effect of implantable cardioverter-defibrillator in non-ischemic heart failure according to background medical therapy: Extended follow-up of the DANISH trial

Background The Heart Failure Collaboratory (HFC) score integrates types and doses of guideline-directed pharmacotherapies for heart failure (HF) with reduced ejection fraction (HFrEF). We examined the effect of implantable cardioverter-defibrillator (ICD) implantation according to modified HFC (mHFC) score in 1,116 patients with non-ischemic HFrEF from the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic HF on Mortality (DANISH). Methods and Results Patients were assigned scores for renin-angiotensin-system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists (0: no use; 1: <50% of maximum dose; 2: ≥50% of maximum dose). The maximum score was 6, corresponding to ≥50% of maximum dose for all therapies. The median baseline mHFC score was 4, and the median follow-up was 9.5 years. Compared with mHFC score=3-4, mHFC score=1-2 was associated with a higher rate of all-cause death (mHFC=1-2: adjusted HR 1.67 [95%CI,1.23-2.28]; mHFC=3-4, reference; mHFC=5-6: adjusted HR 1.07 [95%CI,0.87-1.31]). ICD implantation did not reduce all-cause death compared with control (reference) (HR 0.89 [95%CI,0.74-1.08]) regardless of mHFC score (mHFC=1-2: HR 0.98 [95%CI,0.56-1.71]; mHFC=3-4: HR 0.89 [95%CI,0.66-1.20]; mHFC=5-6: HR 0.85 [95%CI,0.64-1.12]; Pinteraction, 0.65). Similarly, ICD implantation did not reduce cardiovascular death (HR 0.87 [95%CI,0.70-1.09]) regardless of mHFC score (Pinteraction, 0.59). The ICD group had a lower rate of sudden cardiovascular death (HR, 0.60 [95% CI,0.40-0.92]); this association was not modified by mHFC score (Pinteraction, 0.35). Conclusions Lower mHFC scores were associated with higher rates of all-cause death. ICD implantation did not result in an overall survival benefit in patients with non-ischemic HFrEF regardless of mHFC score.