Coronary Angiography after Cardiac Arrest without ST-Segment Elevation

Trial Design and Oversight

The COACT trial was an investigator-initiated, randomized, open-label, multicenter trial that compared a strategy of immediate coronary angiography with a strategy of delayed angiography in patients who had been successfully resuscitated after cardiac arrest and who did not have ST-segment elevation on ECG. The trial design has been published previously.14 The protocol, available with the full text of this article at, was designed by the authors and was approved by the trial steering committee and all relevant ethics committees.

The trial was sponsored by the Netherlands Heart Institute, Biotronik, and AstraZeneca. The sponsors of the trial had no role in the design or monitoring of the trial; the selection of the participating centers; the enrollment of participants; the collection, recording, storage, retention, or analysis of the data; the writing of the manuscript; or the decision to submit the manuscript for publication.

A clinical research organization (Clinical Research Unit Cardiology VUmc) was responsible for maintaining and monitoring the patient data. A data and safety monitoring committee oversaw the trial. All coronary angiography and PCI procedures were evaluated at an independent core laboratory by personnel who were unaware of the treatment assignments. The authors vouch for the accuracy and completeness of the data and analyses and for the fidelity of the trial to the protocol (see the Supplementary Appendix, available at


Patients were eligible for the trial if they had had an out-of-hospital cardiac arrest with an initial shockable rhythm and were unconscious after the return of spontaneous circulation. Patients were excluded if they had signs of STEMI on ECG in the emergency department, shock, or an obvious noncoronary cause of the arrest. Further inclusion and exclusion criteria and definitions are provided in the Supplementary Appendix. Deferred written informed consent was obtained from all enrolled patients with the use of a prespecified procedure (see the Supplementary Appendix).

Randomization and Treatment

Patients were screened for eligibility in the emergency department. Eligible patients were randomly assigned in a 1:1 ratio with the use of a Web-based randomization system (Castor EDC) 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. If a patient who had initially been assigned to the delayed angiography group showed signs of cardiogenic shock, recurrent life-threatening arrhythmias, or recurrent ischemia during hospitalization, urgent coronary angiography was performed.

The choice of anticoagulant and the revascularization strategy were left to the discretion of the treating physicians, although it was recommended that all coronary lesions suspected of being unstable should be treated. (Unstable lesions were defined as coronary lesions with at least 70% stenosis and the presence of characteristics of plaque disruption, including irregularity, dissection, haziness, or thrombus, as assessed by results of coronary angiography.) 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. The SYNTAX score reflects a comprehensive angiographic assessment of the coronary vasculature, with scores of 22 or lower indicating low anatomical complexity, scores of 23 to 32 indicating intermediate anatomical complexity, and scores of more than 32 indicating high anatomical complexity (0 is the lowest score, and there is no upper limit).15 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.

Further postresuscitation care was in line with international resuscitation guidelines.10 Targeted temperature management was initiated as soon as possible and was performed in accordance with local protocol. The approach to withdrawal of life-sustaining treatment for patients with persistent coma was not prespecified and was based on local practice, which adhered to Dutch and European guidelines.

Follow-up and End Points

Follow-up data were obtained by means of a telephone interview conducted 90 days after randomization with the patient or a family member or were determined from information acquired from the patient’s general physician. The primary end point of the trial was survival at 90 days. Secondary end points included survival at 90 days with good cerebral performance or mild or moderate disability, myocardial injury quantified on the basis of troponin levels, increase in creatine kinase and creatine kinase MB levels (reported as the area under the curve), acute kidney injury defined according to Acute Kidney Injury Network criteria,16 the need for renal-replacement therapy, time to target temperature, duration of catecholamine or inotropic therapy, neurologic status at discharge from the intensive care unit, markers of shock, recurrence of ventricular tachycardia requiring defibrillation or electrical cardioversion, duration of mechanical ventilation, and major bleeding defined according to Thrombolysis in Myocardial Infarction (TIMI) criteria. A detailed description of biomarker measurements and definitions of outcome measures are provided in the Supplementary Appendix.

Statistical Analysis

The trial was powered for the primary end point of survival at 90 days. The results of a previous meta-analysis of 10 nonrandomized studies showed that immediate angiography was better than conventional treatment with respect to overall survival (56% vs. 32%; odds ratio, 2.78; 95% confidence interval [CI], 1.89 to 4.10).17 We therefore hypothesized that in our trial, more patients in the immediate angiography group than in the delayed angiography group would survive to 90 days. We 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), when assessed by means of a chi-square test at a two-sided significance level of 5%. The sample size was increased by 10% to a total of 552 patients to account for loss of patients to follow-up.

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. 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. After this interim analysis, the data and safety monitoring committee advised that the sample size not be increased.

Outcome measures were assessed in all randomly assigned patients, except in those for whom written informed consent was retroactively withdrawn. Categorical data (primary and secondary end points) were compared with the use of the chi-square test or Fisher’s exact test and are summarized as numbers and percentages. Odds ratios are reported as effect estimates with 95% confidence intervals. We report the P value only for the primary analysis. The 95% confidence intervals for the secondary end points have not been adjusted for multiplicity, and therefore inferences drawn from these intervals may not be reproducible. Analyses of eight prespecified subgroups were performed. Further details of the statistical analysis are provided in the Supplementary Appendix.

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