Long-Term Follow-Up of DANISH (The Danish Study to Assess the Efficacy of ICDs in Patients With Nonischemic Systolic Heart Failure on Mortality)

Abstract

Background: The Danish Study to Assess the Efficacy of Implantable Cardioverter-Defibrillators (ICDs) in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) found that primary-prevention ICD implantation was not associated with an overall survival benefit in patients with non-ischemic systolic heart failure during a median follow-up of 5.6 years, though there was a beneficial effect on all-cause mortality in patients ≤70 years. This study presents an additional four years of follow-up data from DANISH. Methods: In DANISH, 556 patients with non-ischemic systolic heart failure were randomized to receive an ICD and 560 to receive usual clinical care and followed until June 30, 2016. In this long-term follow-up study, patients were followed until May 18, 2020. Analyses were conducted for the overall population and according to age (≤70 and >70 years). Results: During a median follow-up of 9.5 years (25 th -75 th percentile, 7.9-10.9 years), 208/556 patients (37%) in the ICD group and 226/560 patients (40%) in the control group died. Compared with the control group, the ICD group did not have significantly lower all-cause mortality (HR 0.89 [95%CI,0.74-1.08]; P=0.24). In patients ≤70 years (n=829), all-cause mortality was lower in the ICD group than the control group (117/389 [30%] vs 158/440 [36%]; HR 0.78 [95%CI,0.61-0.99]; P=0.04), whereas in patients >70 years (n=287), all-cause mortality was not significantly different between the ICD and control group (91/167 [54%] vs 68/120 [57%]; HR 0.92 [95%CI,0.67-1.28]; P=0.75). Cardiovascular death showed similar trends (overall, 147/556 [26%] vs 164/560 [29%], HR 0.87 [95%CI,0,70-1.09], P=0.20; ≤70 years, 87/389 [22%] vs 122/440 [28%], HR 0.75 [95%CI,0.57-0.98], P=0.04; >70 years, 60/167 [36%] vs 42/120 [35%], HR 0.97 [95%CI,0.65-1.45], P=0.91). The ICD group had a significantly lower incidence of sudden cardiovascular death in the overall population (35/556 [6%] vs 57/560 [10%]; HR 0.60 [95%CI,0.40-0.92]; P=0.02) and in patients ≤70 years (19/389 [5%] vs 49/440 [11%]; HR 0.42 [95%CI,0.24-0.71]; P=0.0008), but not in patients >70 years (16/167 [10%] vs 8/120 [7%]; HR 1.34 [95%CI,0.56-3.19]; P=0.39). Conclusions: During a median follow-up of 9.5 years, ICD implantation did not provide an overall survival benefit in patients with non-ischemic systolic heart failure. In patients ≤70 years, ICD implantation was associated with a lower incidence of all-cause mortality, cardiovascular death, and sudden cardiovascular death. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00542945.

Role of N-terminal pro-B type natriuretic peptide as a predictor of poor outcomes in patients with HFrEF receiving primary prevention implantable cardioverter-defibrillator therapy: a systematic review and dose–response meta-analysis

“…In contrast, the recent ESC guideline has degraded its recommendation to class IIa 1. The basis for this contentious issue is that the recent The Danish Study to Assess the Efficacy of Implantable Cardioverter-Defibrillators in Patients with Non-ischemic Systolic Heart Failure on Mortality trial revealed that ICD implantation for primary prevention did not substantially reduce all-cause mortality risk in patients with NICM after a median follow-up of 9.5 years 33. Aside from the previously stated stretch-induced arrhythmia mechanism, scar formation resulting from a prior myocardial infarction can also result in ventricular tachyarrhythmias in patients with HF, implying that NT-pro BNP as a parameter of ventricular dilatation may not be solely correlated with appropriate ICD shock in patients with ICM 34.…”

Incidence, risk assessment and prevention of sudden cardiac death in cardiomyopathies

“…However, there was no evidence of a heterogeneity in ICD effectiveness depending on the presence of a CRT. 14 The lack of benefit with primary prevention ICD was subsequently confirmed in a long-term follow-up of the DAN-ISH trial patients (median 9.5 years), 76 as well as in a subgroup of patients with non-ischaemic HFrEF form the SCD-HeFT trial, followed for a median of 11 years. 77 However, the original DAN-ISH trial did show a significant risk reduction in all-cause and cardiovascular mortality in patients <70 years of age, 15 which was maintained over an extended follow-up.…”

New perspectives in diagnosis and risk stratification of non-ischaemic dilated cardiomyopathy

“…The DANISH trial results, 19 preceded by SCDHEFT and DEFINITE, put in discussion the effects on global survival after ICD implantation in patients with non-ischaemic DCM heart failure and ejection fraction ≤35%, despite acknowledging the significant impact on SCD among younger patients. In the latest 2022 ESC guidelines, according to these results, primary prevention ICD implantation in non-ischemic DCM grade of recommendation was lowered from IA to IIa-A; it must be underlined, although, that subgroups at high risk of SCD exist, and the indication to implantation should be individually evaluated and tailored on the patient.…”