Lower versus higher blood pressure targets during intensive care of comatose patients resuscitated from out-of-hospital cardiac arrest - A Bayesian analysis of the BOX trial

Background: The Blood Pressure and Oxygenation Targets After out-of-hospital cardiac arrest (BOX) trial found no statistically significant differences in mortality or neurological outcomes with mean arterial blood pressure targets of 63 versus 77 mmHg in patients receiving intensive care post-cardiac arrest. In this study, we aimed to evaluate the effect on 1-year mortality and assess heterogeneity in treatment effects (HTE) using Bayesian statistics.

Methods: We analyzed 1-year all-cause mortality, 1-year neurological outcomes, and plasma neuron-specific enolase (NSE) at 48 hours using Bayesian logistic and linear regressions primarily with weakly informative priors. HTE was assessed according to age, plasma lactate, time to return of spontaneous circulation, primary shockable rhythm, history of hypertension, and ST-segment elevation myocardial infarction. Absolute and relative differences are presented with probabilities of any clinical benefit and harm.

Results: All 789 patients in the intention-to-treat cohort were included. The risk difference (RD) for 1-year mortality was 1.5%-points (95% credible interval [CrI]: -5.1 to 8.1), with <33% probability of benefit with the higher target. There was 33% probability for a better neurological outcome (RD: 1.5%-points; 95% CrI: -5.3 to 8.3) and 35.1% for lower NSE levels (mean difference: 1.5 µg/L, 95% CrI: -6.0 to 9.1).HTE analyses suggested potential harms of the higher blood pressure target in younger patients.

Conclusions: The effects of a higher blood pressure target on overall mortality among comatose patients resuscitated from out-of-hospital cardiac arrest were uncertain. A potential effect modification according to age warrants additional investigation.

Clinical trial registration: ClinicalTrials.gov ID NCT03141099.