ICU Journal Club- COACT Trial

Dr Swapnil Pawar & Dr Jose Chacko

Coronary Angiography after Cardiac Arrest without ST-Segment Elevation

Lemkes et al https://www.nejm.org/doi/10.1056/NEJMoa1816897

Background –

Out-of-hospital cardiac arrest is a leading cause of death.  A recent study reported a mortality of approximately 40% among patients who had been successfully resuscitated after out-of-hospital cardiac arrest associated with ventricular fibrillation or pulseless ventricular tachycardia.  The most frequent cause of cardiac arrest is ischemic heart disease, and coronary artery disease has been reported in up to 70% of patients who have been resuscitated and are referred for immediate coronary angiography.  However, the cause of arrest is often unclear immediately after the event, and the lack of a definitive diagnosis can lead to uncertainty regarding the appropriate treatment.  If myocardial infarction is the cause of the arrest, immediate percutaneous coronary intervention (PCI) might salvage myocardium, improve circulatory function, and prevent the recurrence of life-threatening arrhythmias. Current European and American guidelines recommend immediate coronary angiography with PCI in patients who present with ST-segment elevation myocardial infarction (STEMI) and cardiac arrest.  In patients with cardiac arrest who do not have ST-segment elevation on electrocardiography (ECG), the role of immediate coronary angiography is still a matter of debate.

What’s Known – 

Data from randomized trials are lacking, and observational studies have shown conflicting results regarding the effect of immediate coronary angiography and PCI on outcomes in this patient group. At present, international guidelines on cardiopulmonary resuscitation recommend emergency coronary angiography in selected patients after out-of-hospital cardiac arrest, even in the absence of ST-segment elevation.

Hypothesis – in patients who are successfully resuscitated after cardiac arrest in the absence of STEMI, a strategy of immediate coronary angiography (and PCI if necessary) would be better than a strategy of delayed angiography with respect to overall survival.

Methods- 

Design- The COACT trial was an investigator-initiated, randomized, open-label, multicenter trial conducted in 19 centres from Netherlands  January 2015 through July 2018. The trial had an adaptive design that allowed for an increase in sample size if the survival benefit was substantial but smaller than the 40% difference mentioned above.

Inclusion Criteria – Patients who had an out-of-hospital cardiac arrest with an initial shockable rhythm and were unconscious after the return of spontaneous circulation.

Exclusion Criteria- Patients were excluded if they had signs of STEMI on ECG in the emergency department, shock, or an obvious noncoronary cause of the arrest.
Randomisation– Eligible patients were randomly assigned in a 1:1 ratio with the use of a Web-based randomization system.  to either immediate angiography or delayed angiography. In the immediate angiography group, coronary angiography was performed as soon as possible and was initiated within 2 hours after randomization. In the delayed angiography group, coronary angiography was performed after neurologic recovery, in general after discharge from the intensive care unit.
Sample Size- powered for the primary endpoint of survival at 90 days. Authors calculated that 251 patients would need to be enrolled in each group to give the trial 85% power to detect a 40% difference between the immediate angiography group and the delayed angiography group in terms of survival to 90 days (45% survival with immediate angiography vs. 32% with delayed angiography),This was based on the previous meta-analysis which showed immediate angiography was better than routine care ( 56% vs 32%). The sample size was increased by 10% to a total of 552 patients to account for the loss of patients to follow-up. The data and safety monitoring committee of the trial was allowed to recommend an increase in the sample size on the basis of the results of an interim analysis of outcomes in the first 400 patients.
Key Characteristics in the protocol- 

1. The crossover was permitted if the patient in delayed angiography group showed signs of cardiogenic shock, recurrent life-threatening arrhythmias, or recurrent ischemia.
2. The choice of anticoagulant and the revascularization  strategy were left to the discretion of the treating physicians
3. In patients with multivessel disease, treating physicians were advised to use a revascularization strategy that was based on the local heart team protocol and the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score
4. If coronary-artery bypass grafting was the treatment of choice for a patient in the immediate angiography group, this procedure could be deferred until after neurologic recovery.
5. TTM as per local protocol and was initiated as soon as possible.
6. Withdrawal of treatment as per local protocol based on Dutch and European guidelines

Results- 

N= 273 ( Immediate Angiography) N=265 ( Delayed Angiography)

Primary Outcome – 

Survival at 90 days- No difference – 64.5% in immediate angiography group vs 67.2 % in delayed angiography group.

Secondary Outcomes –

1. Survival with good neurological recovery as assessed by CPC score- No difference. CPC 1 57.7 vs 60 %, CPC 5- 35.7 vs 33%
2. Survival until hospital discharge- 65.2 vs 68.7%
3. GCS at ICU discharge – 14-15 in each group.
4. Renal failure- AKIN grading -Need for dialysis- 2.9% vs 4.2 %
5. Time to establish TTM- no difference
6. Duration of inotropic/vasopressor support- no difference 
7. Markers of shock such as MAP or Lactate unto day 3 – no difference
8. Duration of Mechanical ventilation – no difference – 2.3 vs 2.2 days

Strengths  – 

1. Multi-centre RCT with Adaptive design
2. Minimal crossover- 13 patients in immediate underwent delayed and 3 in delayed underwent immediate angiography
3. 90% patients – received TTM and that too in < 5 hours and 90% of them were on MV
4. Strict adherence to protocol
5. Good follow up
6. Challenged the results of previous observational studies
7. Angiography findings – Majority had stable coronary lesions. Only 5% had thrombotic occlusion. Similar results in patients without cardiac arrest.
8. Neurological injury is the main cause of death rather cardiac cause – Factors around post-resuscitation care are more important rather the treatment of the actual cause

Limitations- 

1. Not blinded
2. Doesn’t apply to patients who were in shock, renal failure and persistent St elevation.
3. Patients with initial non-shockable rhythm were not included.
4. 2.5 % patients – withdrew consent
5. Underpowered?? As actual survival was higher than anticipated survival 

Summary –

1. Don’t rush for Coronary angiography if there is No evidence of ST-segment elevation.
2. Good quality and timely Basic life support and protocolised post-resuscitation care can achieve good neurological recovery.
3. Anti-platelet therapy while waiting for angiography is worth considering.
4. The same approach may apply to OHCA patients who had a non-shockable rhythm as the initial rhythm.