Implantable Cardioverter–Defibrillators in Trials of Drug Therapy for Heart Failure: A Systematic Review and Meta‐Analysis

Abstract

BACKGROUND Medical therapy for heart failure with reduced ejection fraction evolved since trials validated the use of implantable cardioverter–defibrillators ( ICD s). We sought to evaluate the performance of ICD s in reducing mortality in the era of modern medical therapy by means of a systematic review and meta‐analysis of contemporary randomized clinical trials of drug therapy for heart failure with reduced ejection fraction. METHODS AND RESULTS We systematically identified randomized clinical trials that evaluated drug therapy in patients with heart failure with reduced ejection fraction that reported mortality. Studies that enrolled <1000 patients, patients with left ventricular ejection fraction >40%, or patients in the acute phase of heart failure and study treatment with devices were excluded. We identified 8 randomized clinical trials, including 31 701 patients of whom 3631 (11.5%) had an ICD . ICDs were associated with a lower risk of all‐cause mortality (relative risk [RR], 0.85; 95% CI, 0.78–0.94) and sudden cardiac death (RR, 0.49; 95% CI, 0.40–0.61). Results were consistent among studies published before and after 2010. In meta‐regression analysis, the proportion of nonischemic etiology did not affect the associated benefit of ICD . CONCLUSIONS In our meta‐analysis of contemporary randomized trials of drug therapy for heart failure with reduced ejection fraction, the rate of ICD use was low and associated with a decreased risk in both all‐cause mortality and sudden cardiac death. This benefit was still present in trials with new medical therapy.

Digital Biomarker–Based Studies: Scoping Review of Systematic Reviews

“…The reported outcomes fell into 13 unique categories of the ICF. Looking after one's health (physical activity; 15/31, 48%) [39][40][41][43][44][45][46][47][48]52,[55][56][57]64,68]; walking (12/31, 39%) [39][40][41][42][43]46,52,56,57,61,62,68]; heart rhythm (8/31, 26%) [49,51,53,54,60,66,67,69]; demographic change (mortality; 7/31, 23%) [49,51,53,54,66,67,69]; and weight maintenance functions (7/31, 23%) [42,[46][47][48]50,55,59] were the most commonly reported outcomes in the studies. Blood pressure functions (3/31, 10%)…”

“…In spite of comprising patients with the aforementioned specific clinical conditions, some SRs also included general populations without an applicable ICD-11 category, such as employees (3/31, 10%) [40,56,61]; students (3/31, 10%) [40,46,50]; healthy participants (2/31, 7%) [40,53]; and office workers (1/31, 3%) [40]. [49,53,66,67]. Percutaneous transluminal destruction of the arrhythmia circuit was covered by 7% (2/31) of the SRs [51,54].…”

“…Digital biomarkers were extracted from the included SRs. In total, 16 physiological and behavioral data groups were identified using the ICF tool, such as looking after one's health (physical activity; 14/31, 45%) [39,40,[43][44][45][46][47][48]52,[55][56][57]64,68]; walking (11/31, 36%) [39][40][41][42][43]52,56,57,61,62,68]; heart rhythm (7/31, 23%) [49,51,53,54,66,67,69]; and weight maintenance functions (7/31, 23%) [42,[46][47][48]50,55,59]. The other identified data can be found in Multimedia Appendices 5 and 6.…”

“…A substantial number of digital biomarkers were used as interventions in the SRs (24/31, 77%) [39][40][41][42][43][44][45][46][48][49][50]52,53,[55][56][57][58][59][60][61][62][65][66][67]. By contrast, digital biomarkers were used to measure outcomes in 10% (3/31) of the studies [47,64,68].…”

Implantable cardioverter-defibrillator therapy in primary versus secondary prevention: Reliable prediction of appropriate therapies and mortality is still an unmet need

“…Certainly, some classes of medical therapy and amiodarone reduce appropriate therapies but are not necessarily connected to a reduction in mortality [5] , [9] . A recent meta-analysis of 8 RCTs of drug therapy for HF, including 31,701 HF patients of whom 11.5% (3645 patients) had an ICD, demonstrated that there were no significant differences in all-cause death and sudden cardiac death in studies published either before or after 2008, and that the use of ICD was consistently associated with a reduced risk of all-cause death and sudden cardiac death, indicating that the impact of ICD on preventing sudden death was not affected by contemporary optimized medical therapy [10] . In addition, the high prevalence of HF medication in patients with electrical storm does not alter the poor outcomes [11] .…”