Does bypass to a cardiac arrest centre improve survival?

JC: The ARREST trial. Does bypass to cardiac arrest centres save lives?

Cardiac arrest is a critical medical emergency that requires a chain of actions to increase the chances of survival and minimize long-term damage. In recent years, the concept of specialized cardiac arrest centers has gained significant attention and enthusiasm based on a number of observational studies and meta-analysis, with the predicted improvement in survival being argued as significant. Cardiac Arrest centers, often established within well-equipped hospitals with on-site cardiology, intensive care and access to PCI also bring together a multidisciplinary team of healthcare professionals, advanced technologies, and streamlined protocols to provide comprehensive care to patients who experience cardiac arrest. It therefore seems likely (maybe even obvious) that these centers improve outcomes and the quality of life for survivors. However, as we have seen many times at St Emlyn’s what appears to be an obvious benefit is frequently a little more complicated than that.

The question is particularly relevant in Virchester as there are plans to institute cardiac arrest centres and bypass protocols for those patients who achieve ROSC in the prehospital setting. To some extent this happens already for those patients who have ECG signs indicative of the need for PCI, but for other patients, the situation is less clear. When I am working in the prehospital environment I have frequently taken patients direct to the PCI centre even if the post-ROSC ECG is non-diagnostic, but where I think that there is a strong likelihood of a cardiac cause. An example would be a middle-aged patient collapsing in a gym, and who was resuscitated following a shock from an AED. They might not meet the official criteria, but I’m reasonably confident it’s a heart problem.

However, anecdote and observational trials are hardly the bedrock of evidence-based medicine and so it is great to see a trial published in the Lancet​1​ that may help us answer the question of whether cardiac arrest centres are as effective as we might hope. The abstract is below, but as always please do read the full paper.

The Abstract – Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial​1​

Background: The International Liaison Committee on Resuscitation has called for a randomised trial of delivery to a cardiac arrest centre. We aimed to assess whether expedited delivery to a cardiac arrest centre compared with current standard of care following resuscitated cardiac arrest reduces deaths.
Methods: ARREST is a prospective, parallel, multicentre, open-label, randomised superiority trial. Patients (aged ≥18 years) with return of spontaneous circulation following out-of-hospital cardiac arrest without ST elevation were randomly assigned (1:1) at the scene of their cardiac arrest by London Ambulance Service staff using a secure online randomisation system to expedited delivery to the cardiac catheter laboratory at one of seven cardiac arrest centres or standard of care with delivery to the geographically closest emergency department at one of 32 hospitals in London, UK. Masking of the ambulance staff who delivered the interventions and those reporting treatment outcomes in hospital was not possible. The primary outcome was all-cause mortality at 30 days, analysed in the intention-to-treat (ITT) population excluding those with unknown mortality status. Safety outcomes were analysed in the ITT population. The trial was prospectively registered with the International Standard Randomised Controlled Trials Registry, 96585404.
Findings: Between Jan 15, 2018, and Dec 1, 2022, 862 patients were enrolled, of whom 431 (50%) were randomly assigned to a cardiac arrest centre and 431 (50%) to standard care. 20 participants withdrew from the cardiac arrest centre group and 19 from the standard care group, due to lack of consent or unknown mortality status, leaving 411 participants in the cardiac arrest centre group and 412 in the standard care group for the primary analysis. Of 822 participants for whom data were available, 560 (68%) were male and 262 (32%) were female. The primary endpoint of 30-day mortality occurred in 258 (63%) of 411 participants in the cardiac arrest centre group and in 258 (63%) of 412 in the standard care group (unadjusted risk ratio for survival 1.00, 95% CI 0.90-1-11; p=0.96). Eight (2%) of 414 patients in the cardiac arrest centre group and three (1%) of 413 in the standard care group had serious adverse events, none of which were deemed related to the trial intervention.
Interpretation: In adult patients without ST elevation, transfer to a cardiac arrest centre following resuscitated cardiac arrest in the community did not reduce deaths.

Patterson T, Perkins GD, Perkins A, et al. Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial. The Lancet. Published online October 2023:1329-1337. doi:10.1016/s0140-6736(23)01351-x

What kind of paper is this?

It’s a randomised controlled trial which is an excellent design here. Patients were randomised to either transport direct to one of 7 cardiac arrest centres or to the nearest hospital (32 hospitals). Four of the cardiac arrest centres had co-located EDs. Patients were randomised in blocks, but were not stratified.

Tell me about the patients

To be clear these were not ‘all’ cardiac arrest patients. Only patients in whom ROSC had been achieved were eligible, any patients with indications for PCI (e.g. ST elevation) were excluded, as were those with an a-priori DNAR. So this is a relatively smaller group of patients who have suffered and initially survived their cardiac arrest. This is important as within this group the aetiology of the cardiac arrest will be somewhat heterogenous and not necessarily cardiac in nature.

Patients were recruited from a cohort of patients attended by the London Ambulance Service (LAS). At baseline, the patients were pretty similar.

What were the interventions?

The primary intervention in this study was transportation decisions. All other aspects of care were standard for LAS, and then within hospital they were left to the discretion of clinicians. For cardiac patients I suspect this was largely protocolised, but for those found to not have a cardiac cause, this would clearly vary.

What about the outcomes?

The principal outcome measure was survival at 30 days. A number of secondary outcomes were examined as is common in these sorts of trials. Notably the authors are looking at 3/12 survival, 6/12 neuro outcomes and will in time give us longer term outcomes and economic evaluations. I think these are pretty reasonable outcomes, especially with the intent of obtaining longer term neuro outcomes in future papers.

What did they find?

862 patients were randomised, and of those we have outcome data on 823. Rather surprisingly, they found no difference in outcomes between the two arms of the study. 258/411 (63%) of patients in the cardiac arrest group, and 258/412 (63%) of the patients in the standard care group died at the 30-day mortality point (RR 1.0, 95% CI 0.9-1.11). At 3 months the difference was 65% vs. 64%, so again no difference. There was no difference in neuro outcomes at discharge or at 3 months.

The results are remarkably similar, and although the authors did not attempt a Bayesian analysis the relatively tight confidence intervals around the principal outcome suggest that it is highly unlikely that any meaningful difference exists.

A number of secondary outcomes were examined and although there were suggestions that younger patients may do better in cardiac arrest centres, this can only be considered hypothesis-generating. Patients in cardiac arrest centres were more likely to have invasive procedures and perhaps more likely to be diagnosed with heart failure, but neither of these differences is likely to substantially change the outcome of the study.

What does this mean?

This is a well-designed study and a very strong result that questions the impact of cardiac arrest centres on improving patient outcome. It is the most significant RCT in this area and greatly adds to the evidence base. It is perhaps surprising, to me at least, that no difference was found at all and it is interesting to see how the paper has been received and the results analysed.

There is no doubt that London is a somewhat atypical healthcare system. It has a single ambulance service, well established protocols, short response times, many hospitals and a range of specialist services available. It is not typical of other geographies or health economies and so may not be widely generalisable. The differences in the availability and capability of hospitals in the London catchment may be less than in other areas, and if there is little difference in post-ROSC care between cardiac arrest centres and other hospitals then we would not expect to find a difference. In the paper there is little discussion of what the real differences are between the various hospitals the patients get taken to and so it’s a little tricky to determine what differences may exist. An analogy may exist here with the original assessment of trauma centres in the UK, which showed no difference between sites. In part that was because the trauma centre sites and the reference sites were in many ways similar.

Rob Major (tweet below) points out that other UK studies have shown a benefit in another subgroup (Utstein-positive​2​ patients), but this is again observational data and thus prone to a number of biases. However, this study is in a very different health environment where the transport times to hospitals may be very different indeed (which may skew results in either direction of course). In addition, the impact of aeromedical options carries across the country and this too may impact on outcomes.

Of note 505/813 patients had a cardiac cause of arrest, and so a number of non-cardiac patients will have ended up in specialist centres who may be less well equipped to deal with them, although this is not explored in the paper. In observational studies​3​, it is entirely possible that those patients with a higher likelihood of an underlying cause are selected for transport to a cardiac arrest centre and those without are transported to a local ED. That is certainly something I have seen locally, and as previously mentioned is something that I have done several times in the past. This may (and it’s only a may) explain the unexpected difference between the previous observational studies and this RCT. Participants were excluded if there was an obvious non-cardiac cause, but the accuracy of that decision may vary depending on many factors

So should we abandon the concept of cardiac arrest centres?

Not necessarily, as it rather depends on what the differences are between the defined cardiac arrest centre and the alternative hospital, plus the geography and availability of other related specialist services. In Virchester I suspect we will be pressing ahead with the proposed changes, but we will keep a close on the data to see if things really do change. However, the onus is now on those who advocate cardiac arrest centres in the UK to rationalise their standpoint based on arguments that might counter the evidence from the ARREST trial.

Well done to LAS and the research team for delivering a fantastic trial.

References

  1. 1.
    Patterson T, Perkins GD, Perkins A, et al. Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial. The Lancet. Published online October 2023:1329-1337. doi:10.1016/s0140-6736(23)01351-x
  2. 2.
    Chamberlain D, Eisenberg M. The Utstein cardiac arrest outcome reports. Resuscitation. Published online February 2009:288-289. doi:10.1016/j.resuscitation.2008.12.006
  3. 3.
    Yeo JW, Ng ZHC, Goh AXC, et al. Impact of Cardiac Arrest Centers on the Survival of Patients With Nontraumatic Out‐of‐Hospital Cardiac Arrest: A Systematic Review and Meta‐Analysis. JAHA. Published online January 4, 2022. doi:10.1161/jaha.121.023806

Cite this article as: Simon Carley, "JC: The ARREST trial. Does bypass to cardiac arrest centres save lives?," in St.Emlyn's, August 30, 2023, https://www.stemlynsblog.org/jc-bypass-to-cardiac-arrest-centres/.

Thanks so much for following. Viva la #FOAMed

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