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
- 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
- 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)
- Immediate angiography (62.9%) vs delayed angiography (64.4%)
- 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)
- No difference in survival with good cerebral performance
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