https://doi.org/10.55788/5aa35654
BOX (NCT03141099) enrolled 789 comatose patients who had been admitted to hospital after resuscitated cardiac arrest and had a sustained return to spontaneous circulation [1–4]. All participants received temperature control at 36°C with mechanical ventilation for at least 24 hours, prior to return to normothermia. BOX was a double-blind, randomised trial with a 2-by-2 factorial design, in which the researchers evaluated a mean arterial blood-pressure target of 63 mmHg as compared with 77 mmHg; patients were also assigned to different oxygen targets. The primary outcome in both arms was a composite of all-cause death or hospital discharge with severe disability or coma (Cerebral Performance Category [CPC] of 3 or 4), whichever came first within 90 days of randomisation.
Oxygenation
Prof. Jacob Eifer Møller (Copenhagen University Rigshospitalet, Denmark), presented the first part, the BOX trial’s oxygen analysis. Participants were randomised to receive either a restrictive target (partial pressure of arterial oxygen [PaO2] of 68–75 mmHg) or a liberal target (PaO2 98–105 mmHg) of oxygenation.
Prof. Møller provided the rationale: “There are translational data and some observational data that suggest that a lot of oxygen may harm the brain,” while other studies have shown “of course, that if you give too little oxygen that can be harmful as well. We wanted to know what is best.”
The trial results showed that there was no difference between the low or high PaO2 groups (32.0% vs 33.9%; HR 0.95; 95% CI 0.75–1.21). BOX was “very conclusive” on this question, said Prof. Møller. “There was absolutely no signal of difference between these groups, and it was very stable in all subgroup analyses and also for the secondary endpoints. So even though it’s neutral, it’s a very consistent signal in this study.” All-cause mortality at 90 days was also not affected by liberal versus restrictive PaO2 targets (31.1% vs 28.7%; not significant).
Blood pressure
The second part of BOX, interrogating the role of blood pressure in OHCA outcomes, was presented by Dr Jesper Kjaergaard (Copenhagen University Rigshospitalet, Denmark). It was hypothesised that a higher mean arterial blood pressure target of 77 mmHg may improve cerebral perfusion. In BOX, the blood pressure comparison was double-blinded due to tweaking the internal calibration of the blood pressure machines, which displayed values 10% above or 10% below the true measurements. Thus, while the study’s stated goal for mean target blood pressure was 70 mmHg, in reality participants were randomised to targets of 63 or 77 mmHg, and the data showed that indeed a 10.5 mmHg difference between the 2 arms was achieved (95% CI 9.9–11.2 mmHg; P<0.0001). The higher blood pressure target was obtained using vasopressors and noradrenaline.
However, again, BOX showed there was no impact on the proportion of patients who died or left the hospital with a CPC of 3 or 4, within 90 days, for those with a target of 73 mmHg compared with a target of 63 mmHg (34% vs 32%; HR 1.08; 95% CI 0.84–1.37). Likewise, all-cause mortality at 90 days was similar between the blood pressure targets (31% vs 29%; HR 1.13; 95% CI 0.88–1.46).
Across both parts of BOX, results were similar across all subgroups, with no interaction between the oxygen and blood pressure targets.
- Møller JE, et al. BOX - Oxygen therapy in comatose OHCA patients. Hot Line Session 2, ESC Congress 2022, Barcelona, Spain, 26–29 August.
- Kjaergaard J, et al. Blood pressure targets in comatose survivors of cardiac arrest. Hot Line Session 2, ESC Congress 2022, Barcelona, Spain, 26–29 August.
- Schmidt H, et al. N Engl J Med. 2022 Aug 27. doi: 10.1056/NEJMoa2208686.
- Kjaergaard J, et al. N Engl J Med. 2022 Aug 27. doi: 10.1056/NEJMoa2208687.
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Table of Contents: ESC 2022
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ESC Clinical Practice Guidelines
Prevention of VT and sudden cardiac death: the new recommendations
New and first ESC cardio-oncology guideline
The 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension
Cardiovascular assessment and management of patients undergoing non-cardiac surgery
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Dapagliflozin DELIVERs for HFmrEF/HFpEF
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Anticoagulation
Rheumatic heart disease-associated AF: standard-of-care holds ground
New anticoagulant safe and maybe effective: PACIFIC-AMI and PACIFIC-Stroke outcomes
AXIOMATIC-SSP: Reducing risk of ischaemic stroke with factor XIa inhibition?
Evolving evidence for P2Y12 inhibition in chronic coronary syndromes: PANTHER
Prevention
Danish study suggests starting CVD screening before age 70
Polypill SECUREs win in secondary prevention in elderly
Long-term therapy with evolocumab associated with lower CV mortality
ARBs + beta-blockers may delay Marfan syndrome aortic root replacement
ENTRIGUE: Subcutaneous pegozafermin in severe hypertriglyceridaemia
Artificial Intelligence & Digital Health – What Is New
First RCT evidence for use of AI in daily practice
AI-enhanced echography supports aortic stenosis patients
Ischaemia
Medical therapy versus PCI for ischaemic cardiomyopathy
Allopurinol disappoints in ALL-HEART
Conservative or invasive management for high-risk kidney disease patients with ischaemia?
Genotype-guided antiplatelet therapy in patients receiving PCI
Other HOTLINE Sessions
BOXing out oxygen and blood pressure targets
Coronary CT angiography diagnostics compared head-to-head
High-dose influenza vaccine: mortality benefit?
FFR-guided decision-making in patients with AMI and multivessel disease
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