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

• [article] Coronary Angiography after Cardiac Arrest without ST-Segment Elevation
• [editorial] Coronary Angiography after Cardiac Arrest — The Right Timing or the Right Patients?
• [further reading] ACCESS to the Cardiac Cath Lab in Patients Without STEMI Resuscitated From Out-of-hospital VT/VF Cardiac Arrest
• [further reading] Direct or Subacute Coronary Angiography in Out-of-hospital Cardiac Arrest (DISCO)

Metadata

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