Changes in study enrollment of patients with non-ischemic cardiomyopathy receiving an ICD for primary prevention: Insights from the APPRAISE ATP study

Abstract Introduction The DANISH study called into question the effectiveness of the ICD in patients (pts) with non-ischemic cardiomyopathy (NIC) and resulted in a downgrade in ESC guidelines from Class I to Class IIA. The effect of these findings on implantation of ICDs in NIC pts in clinical studies has not been well established. Methods Two clinical studies were analyzed before and after the publication of DANISH: MADIT-RIT (2009-2012) and APPRAISE ATP (2017-present). These two studies enrolled globally and implanted ICDs in pts with primary prevention (PP) indications. The proportion of pts with NIC were analyzed between the two studies, both globally and by region: North America (NA) and European Union (EU). In addition, the APPRAISE ATP study was divided into halves to determine if any changes were observed whilst the study was in progress. Continuous variables were analyzed with a t-test and categorical variables were analyzed with a Chi-square test. Due to small numbers, implanted pts outside NA and the EU were not entered into the analysis. Results Demographics for the NIC subgroups are shown in the table below [MADIT-RIT (n=284) and APPRAISE ATP (n=1084)]. When compared to MADIT-RIT, pts in APPRAISE ATP were significantly older, had a higher mean LVEF, and greater prevalence of AF and diabetes. Globally, the proportion of pts with NIC who received ICDs was unchanged between the current APPRAISE ATP study and MADIT-RIT 10 years previously (38.1% vs 39.3%, p=0.91). When analyzed by geography, there was no change in North America (38.0% vs 41.6%, p=0.27). In Europe, however, there was a drop in enrollment of NIC ICD pts from 38.6% in MADIT-RIT to 29.1% in APPRAISE ATP. This decline was 24.6% in relative terms and approached, but did not achieve, statistical significance (p=0.074). Implant rates in NIC ICD pts were stable overall when comparing the first half of APPRAISE ATP to its second half. Rates were also stable across both halves in NA and while implant rates of NIC ICD pts appeared to rebound in the second half in the EU, that late increase was not statistically significant. Conclusions The results of the DANISH study appear to have had a limited global impact on enrollment of NIC pts requiring implant of a PP ICD into the APPRAISE ICD clinical study. Whilst there was no change in North America before and after DANISH, there is a signal in the data that investigators in the EU may have restricted implants initially but eventually relaxed as time progressed. Further investigation is needed to confirm whether physicians in general practice have altered their referral patterns.