Time-trend treatment effect of cardiac resynchronization therapy with or without defibrillator on mortality: a systematic review and meta-analysis

This study aimed to investigate the impact of cardiac resynchronization therapy with a defibrillator (CRT-D) on mortality, comparing it with CRT with a pacemaker (CRT-P). Additionally, the study sought to identify subgroups, evaluate the time trend in treatment effects, and analyze patient characteristics, considering the changing indications over the past decades.

PubMed, CENTRAL, and Embase up to October 2021 were screened for studies comparing CRT-P and CRT-D, focusing on mortality. Altogether 26 observational studies were selected comprising 128 030 CRT patients, including 55 469 with CRT-P and 72 561 with CRT-D device. Cardiac resynchronization therapy with defibrillator was able to reduce all-cause mortality by almost 20% over CRT-P [adjusted hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.76–0.94; P < 0.01] even in propensity-matched studies (HR: 0.83; 95% CI: 0.80–0.87; P < 0.001) but not in those with non-ischaemic aetiology (HR: 0.95; 95% CI: 0.79–1.15; P = 0.19) or over 75 years (HR: 1.08; 95% CI 0.96–1.21; P = 0.17). When treatment effect on mortality was investigated by the median year of inclusion, there was a difference between studies released before 2015 and those thereafter. Time-trend effects could be also observed in patients’ characteristics: CRT-P candidates were getting older and the prevalence of ischaemic aetiology was increasing over time.

The results of this systematic review of observational studies, mostly retrospective with meta-analysis, suggest that patients with CRT-D had a lower risk of mortality compared with CRT-P. However, subgroups could be identified, where CRT-D was not superior such as non-ischaemic and older patients. An improved treatment effect of CRT-D on mortality could be observed between the early and late studies partly related to the changed characteristics of CRT candidates.