COACT

Coronary Angiography after Cardiac Arrest without ST-Segment Elevation

J. Lemkes et al. New England Journal of Medicine 2019; doi:10.1056/NEJMoa1816897

Clinical Question

  • In adult patients who have sustained an out of hospital arrhythmia-associated cardiac arrest without an ST-elevation myocardial infarction, is immediate angiography superior to delayed angiography in improving 90-day survival?

Background

  • Percutaneous coronary intervention has been shown to improve mortality in patients with ST-elevation myocardial infarction (STEMI)
  • The benefit of early angiography in post-cardiac arrest patients with no STEMI is uncertain.
  • Data from observational studies has suggested that early coronary intervention may provide a survival benefit in these patients
  • The incidence of coronary artery disease is high in this group of patients, however a randomised controlled trial assessing thrombolysis in all-comers following out of hospital arrest showed no survival benefit
  • This is the first randomised controlled trial (RCT) assessing early angiography in patients who have an out of hospital cardiac arrest without STEMI
  • Two further RCTs are currently recruiting patients in an attempt to answer this question ACCESS trial; DISCO trial

Design

  • Investigator-initiated, randomised, open-label, multicentre trial
  • Patients randomised in a 1:1 ratio with the use of a web-based randomisation system
  • Study powered at 85% power to detect a 40% relative difference in 90-day survival between the immediate angiography and delayed angiography groups
  • Adaptive design that allowed for an increase in sample size if survival benefit was substantial but smaller than the 40% relative difference
  • Data and Safety Monitoring Board was allowed to recommend an increase in sample size after an interim analysis

Setting

  • 19 participating centres in the Netherlands
    • The majority of patients were recruited in the major tertiary centres in Amsterdam and Rotterdam
  • January 2015 – July 2018

Population

  • Inclusion: Patients who had an out of hospital arrest with an initial shockable rhythm and who were unconscious after return of spontaneous circulation (ROSC)
  • Exclusion:
    • Signs of STEMI on the ECG at the emergency department (including new LBBB or isolated ST depression in V1-V3 due to an true posterior infarct)
    • Hemodynamic instability unresponsive to medical therapy
      • Defined as a prolonged (>30 min) systolic blood pressure <90 mmHg at the time of screening
    • An obvious or suspected non-coronary cause of the arrest
    • A known severe renal dysfunction (GFR<30 ml/min)
    • Obvious or suspected pregnancy
    • Suspected or confirmed acute intracranial bleeding
    • Suspected or confirmed acute stroke
    • Known limitations in therapy or DO Not Resuscitate-order
    • Known pre-arrest Cerebral Performance Category 3 or 4
    • >4 hours (from return of spontaneous circulation to screening)
    • Refractory ventricular arrhythmia
    • Known inability to complete 90-day follow-up
  • 538 patients randomised
  • Baseline variables were similar between the two groups apart from immediate angiography group had a longer median time to target temperature (5.4 vs 4.7 hours)

Intervention

  • Coronary angiography as soon as possible and initiated within 2 hours after randomisation

Control

  • Coronary angiography performed after neurological recovery, in general after discharge from the Intensive Care Unit

Management common to both groups

  • If patients showed signs of cardiogenic shock, recurrent life-threatening arrhythmias, or recurrent ischaemia during hospitalisation, urgent angiography was performed
  • Choice of anticoagulant and revascularisation strategy left to the discretion of the treating physicians
  • All coronary lesions suspected of being unstable recommended for treatment
    • Unstable lesions defined as coronary lesions with at least 70% stenosis and the presence of characteristics of plaque disruption
  • In patients with multi-vessel disease, treating physicians were advised to use a revascularisation strategy that was based on local protocol and the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score – this is a complexity score for coronary angiography
  • Post-resuscitation care was in line with international resuscitation guidelines
  • Targeted temperature management was initiated as soon as possible, according to local protocol

Outcome

  • Primary outcome: No statistical difference in survival at 90 days
    • 176 of 273 patients (64.5%) in the immediate angiography group and 178 of 265 patients (67.2%) in the delayed angiography group were alive at 90 days
      • Odds ratio: 0.89 (95% CI 0.62 to 1.72; p=0.51)
    • Deaths: 3 x more likely to be due to a neurological, rather than a cardiac cause
    • Comparing immediate angiography group vs delayed angiography group
      • Median time from randomisation to coronary angiography: 0.8 hours vs 119.9 hours
      • Acute thrombotic occlusion found in 3.4% vs 7.6% of patients
      • PCI was performed in 33.0% vs 24.2% of patients
    • Patients assigned to the strategy of immediate angiography were more often treated with a glycoprotein IIb/IIIa inhibitor
  • Secondary outcomes:
    • No difference in survival with good cerebral performance
      • Immediate angiography (62.9%) vs delayed angiography (64.4%)
        • OR 0.94 (CI 0.66 to 1.31)
    • No difference in the following:
      • Survival to ICU discharge
      • Major bleeding
      • Recurrence of arrhythmia
      • Time of inotrope support
      • Duration of mechanical ventilation
      • Need for renal replacement therapy
    • The immediate angiography group took longer to achieve targeted temperature than the delayed angiography group
      • 5.4 hours vs. 4.7 hours
      • OR 1.19 (95% CI 1.04 to 1.36)

Authors’ Conclusions

  • In this randomised, multicenter trial involving patients who were successfully resuscitated after out-of-hospital cardiac arrest and who had a shockable rhythm and no signs of STEMI or a non-coronary cause of the arrest, a strategy of immediate angiography was not better than a strategy of delayed angiography with respect to overall survival at 90 days

Strengths

  • This study addressed an important area of research in cardiac arrest management
  • Appropriately powered to detect a difference in a patient-centred outcome
  • Patients were well-matched at baseline
  • Post cardiac arrest management in the Netherlands is likely to be similar to most developed world ICU settings
  • A standardised approach was used for coronary intervention
  • The adaptive study design would have allowed for an adjustment in the sample size if this had been necessary
  • There was minimal crossover between study arms and an intention to treat analysis was used
  • The randomisation process was robust and patients were well separated in delivery of the intervention
  • The subgroup analysis is hypothesis generating for future studies assessing potentially higher risk groups (e.g. age > 70 years of age)

Weaknesses

  • External validity is limited by the study only being performed in the Netherlands
  • Blinding was not possible due to the nature of the intervention
  • The difference in time to targeted temperature management between the study arms may have been a confounding factor
  • The predicted relative improvement in 90-day survival of 40% was unrealistic for the potential benefit in the timing of a single intervention
  • Acute unstable coronary lesions were found in only 20% of the trial cohort
  • Coronary interventions were performed in fewer than 40% of patients
  • Narrower inclusion criteria may have identified a higher-risk group of patients

The Bottom Line

  • In patients who have had an out of hospital cardiac arrest without ST elevation myocardial infarction, who have no evidence of cardiogenic shock or recurrent arrhythmias, a strategy of good supportive management without the need for immediate coronary intervention, would seem reasonable in most instances, based on this well-performed study.
  • I would still advocate for early angiography in patients with a good history of ischaemic symptoms prior to arrest and in those with a significant cardiac history
  • I await the publication of the ACCESS and DISCO studies to further refine my practice

External Links

Metadata

Summary author: Fraser Magee
Summary date: 5th April 2019
Peer-review editor: Steve Mathieu

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.