Blood-pressure targets in comatose survivors of cardiac arrest with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention - a BOX sub-study

Abstract

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation. Background After successful resuscitation from out-of-hospital cardiac arrest (OHCA), patients who remain comatose often need hemodynamic support with vasoactive drugs in order to secure an adequate perfusion pressure to vital organs. However, evidence regarding specific blood-pressure targets is sparse, and patients with concomitant heart disease such as acute ST-elevation myocardial infarction (STEMI) might benefit from a lower afterload and lower doses of vasoactive drugs. Purpose To assess the impact of blood-pressure on biochemical infarct size in comatose survivors of OHCA with STEMI and, further, to investigate whether a high or low mean arterial blood-pressure target is superior in preventing death or severe brain injury. Methods The BOX study (n=789) is a randomized trial with a 2-by-2 factorial design which evaluated a double-blind intervention of a high (77 mmHg) versus a low (63 mmHg) mean arterial blood-pressure target in comatose survivors of OHCA of presumed cardiac cause. In this pre-specified sub-study we included patients who had an initial electrocardiogram with STEMI recorded after return of spontaneous circulation (ROSC). The primary outcome was creatine kinase (CK), creatine kinase MB (CKMB), and troponin T (TnT) levels measured at 48 hours as surrogate markers of infarct size. A secondary outcome was a composite of all-cause death within one year from admission or discharge from the hospital with a Cerebral Performance Category (CPC) of 3 to 4, indicating severe neurological disability or a comatose or vegetative state. Results A total of 350 patients were included. Mean time to ROSC was 21±13 minutes. The mean age was 63±12 years and approximately 4 out of 5 were male. The prevalence of relevant prior medical history was as follows; hypertension 42%, diabetes 12%, chronic ischemic heart disease 20%, percutaneous coronary intervention 11%, coronary artery bypass grafting 4%, and congestive heart failure 10%. Mean CK, CKMB and TnT measured at 48 hours did not differ between the two blood-pressure target groups (p=0.42, p=0.14 and p=0.65, respectively). Within one year, 138 patients (39%) had died or been discharged with a CPC of 3 to 4 with no difference found between high or low blood pressure targets (hazard ratio, 1.02; 95% CI, 0.73-1.43; p=0.9). Conclusion Targeting a high versus a low mean arterial blood-pressure in comatose survivors of OHCA with STEMI did not affect infarct size estimated by coronary biomarkers at 48 hours nor did it result in a significant difference in death or severe neurologic disability. Although not evaluating side effects, this study thus suggests that the use of pharmacologic circulatory support in post-resuscitation care can be limited.