Impact of early administration of beta-blocker and RAS inhibitor during VA-ECMO treatment for cardiogenic shock; the post-hoc study of the EARLY-UNLOAD trial

Abstract

Abstract Funding Acknowledgements None. Background/introduction No data about timing and impact of beta-blocker (BB) or renin-angiotensin-aldosterone system inhibitor (RASi) administration for cardiogenic shock (CS) treated with venoatrial extracorporeal membrane oxygenation (VA-ECMO). Purpose To analyze an impact of early administration of BB or RASi during VA-ECMO treatment. Methods This study is a post-hoc analysis of the EARLY-UNLOAD trial (NCT04775472), the trial evaluated an impact of an early prophylactic unloading strategy using left atrial cannulation (LAC) performed within 12 hours from the initiation of VA-ECMO treatment for CS. Among total population (N=116), patients whose lactate was normalized during VA-ECMO and survived more than 2 days were included in this analysis (N=103). Patients were classified whether each medication (BB, RASi or one of BB or RASi) was administered during VA-ECMO or not. The primary endpoint was all-cause mortality. Survival analysis for a primary outcome and landmark analysis for all-cause mortality during different periods (<10 days, 10 to 30 days) were performed. Results BB, RASi, and BB or RASi were administered in 71.8%, 72.8%, and 83.5% of patients, respectively, during VA-ECMO treatment. In early treatment groups, Both BB and RASi were initiated on day 1 (as median). Duration of VA-ECMO treatment was longer in a group who treated with BB during VA-ECMO (8.5 days, vs 5.0 days as median, P = 0.003), and for RASi, it was comparable (8.0 days vs 7.0 days, P = 0.609). Incidence of 30-day all-cause mortality at were statistically comparable between groups (figure 1). The results of survival analysis are described in the figure 2. In Kaplan-Meier analysis, BB, RASi, and BB or RASi during VA-ECMO treatment was not associated with lower probability of 30-day all-cause mortality. Landmark analysis, however, showed lower probability of 10-day mortality in the group treated with BB (P by log-rank test = 0.045), RASi (P = 0.008) and BB or RASi (P=0.005) during VA-ECMO. Multivariate Cox proportional modellings also provided lower risk of 10-day all-cause mortality in groups with BB treatment (Hazard ratio [HR] = 0.26, 95% confidence interval [CI]=0.10-0.69, P = 0.007), RASi treatment (HR = 0.22, 95% CI = 0.08-0.56, P = 0.001) or BB or RASi (HR = 0.15, 95% CI = 0.05-0.41, P < 0.001) during VA-ECMO. RASi (HR = 0.47, 95% CI = 0.22-0.97, P = 0.041) or BB or RASi (HR = 0.37, 95% CI = 0.15-0.93, P = 0.038) treatment during VA-ECMO was also associated with lower risk of 30-day all-cause mortality. Conclusions In this post-hoc analysis of the EARLY-UNLOAD trial, administration of BB or RASi during VA-ECMO treatment for CS was associated with lower risk of short-term mortality.