Response by Schrage et al to Letter Regarding Article, “Association Between Use of Primary-Prevention Implantable Cardioverter-Defibrillators and Mortality in Patients With Heart Failure: A Prospective Propensity Score-Matched Analysis From the Swedish Heart Failure Registry”
Authors: Benedikt Schrage, Cecilia Linde, Frieder Braunschweig, Gianluigi Savarese
Journal: Circulation (2020)

In Response:We thank Dr Littmann for his interest in our study on the association between primary-prevention implantable cardioverter-defibrillator (ICD) use and allcause mortality in patients with heart failure from the Swedish Heart Failure Registry. 1 We agree with Dr Littmann's conclusion that further trials are needed in this area.However, comparing the results of our analysis with those of the DANISH trial (Danish ICD Study in Patients With Dilated Cardiomyopathy) is challenging.First, the etiology was mixed in our observational study, whereas, as pointed out by Dr Littmann, the DANISH trial exclusively enrolled patients with nonischemic cardiomyopathy to investigate the efficacy of primary-prevention ICD use in a randomized controlled trial setting. 1,2Therefore, the aims of DANISH and our study were different.Second, comparing the results of DANISH with our subgroup analysis should be done with caution.We assessed the interaction between ICD use and history of ischemic heart disease rather than ischemic cardiomyopathy as etiology 1,2 because our registry data did not allow us to assess the pathogenesis.The reasons for primary-prevention ICD reducing sudden cardiac death but not all-cause death in the DANISH trial have previously been debated.The late alignment of the Kaplan-Meier curves might suggest a lack of sufficient statistical power to detect differences in all-cause mortality over such a long follow-up (up to ≈8 years).In addition, the high use of cardiac resynchronization therapy (almost 60%), which could have interfered with ICD efficacy as a result of disease modification, 2 might raise concerns about statistical power.The evidence of improved survival with ICD use from meta-analyses including data from DANISH could confirm potential statistical power issues in the trial but might also be driven by the greater ICD treatment effect shown in trials enrolling patients using less contemporary treatments, as Dr Littmann correctly states. 3,4ur study groups were well matched, and thus, heart failure treatments were comparable in patients receiving and those not receiving ICD. 1 In addition, there was no difference in risk of the negative control outcome across the study groups. 1 These findings might potentially indicate that all patients received similar quality of care.However, as Dr Littmann states, we cannot exclude that unmeasured aspects of quality of care might have affected our results.It should be acknowledged that the value of our study lies in its real-world nature and the contemporary treatment of the study population. 1 Our findings indicate that primary-prevention ICD use might still be associated with reduced mortality, although the magnitude of the risk reduction seems to be smaller than anticipated on the basis of past trials. 1Thus, we would like to