By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
Dr. Zimmet reports no financial relationships relevant to this field of study.
SYNOPSIS: In this first-ever randomized trial about comatose patients without ST-segment elevation who have been resuscitated from cardiac arrest, immediate coronary angiography showed no benefit over delayed coronary angiography in terms of 90-day survival.
SOURCE: Lemkes JS, Janssens GN, van der Hoeven NW, et al. Coronary angiography after cardiac arrest without ST-segment elevation. N Engl J Med 2019;380:1397-1407.
It is just after midnight, and the ED is calling. A 65-year-old patient has just been brought in after successful resuscitation from cardiac arrest, with an initial rhythm of ventricular fibrillation that responded to a shock in the field. The patient is hemodynamically stable on a ventilator, and the ECG shows only nonspecific ST changes. Do you take the patient to the cath lab overnight?
Until now, this question has come with plenty of controversy and few data. Enter the COACT study, a prospective randomized trial comparing immediate with delayed coronary angiography in patients who remain comatose after cardiac arrest with an initial shockable rhythm (ventricular fibrillation or tachycardia). Patients who showed ST elevation on ECG, were in shock, or had a clear noncardiac cause for arrest were excluded from the trial. Over the 3.5-year course of the trial, 552 patients were enrolled at 19 centers in the Netherlands and were randomized 1:1 to one of the two treatments. Patients in the immediate angiography group had a median time from arrest to cardiac cath of 2.3 hours vs. 121.9 hours in the delayed angio group. Ultimately, investigators performed cardiac cath in 97.1% of patients in the immediate group vs. 64.9% of patients in the delayed group. Similar to prior observational studies, obstructive coronary disease was found in approximately 65% of patients. However, an acute thrombotic occlusion was found in only 3.4% of patients in the immediate angiography group and in 7.6% of patients in the delayed angiography group. Researchers performed percutaneous coronary intervention in 33% of patients in the immediate angio group and in 24.2% of patients in the delayed group. Coronary artery bypass grafting was performed in 6.2% and 8.7%, respectively. Patients in the delayed angio group were more likely to receive aspirin and P2Y12 inhibitors, while those in the immediate angio group were more likely to receive glycoprotein IIb/IIIa inhibitors.
Crossovers were uncommon, with 13 patients assigned to immediate angiography treated with a delayed approach and three patients in the delayed group treated with an immediate approach. In addition to these, 38 patients in the delayed group ended up with clinically indicated urgent cardiac catheterization prior to their planned procedure for reasons including the development of ST elevation, recurrent ventricular arrhythmia, and cardiogenic shock.
Regarding the primary outcome of survival at 90 days, there was no difference between the two groups. A total of 176 of 273 patients in the immediate angiography group and 178 of 265 patients in the delayed angiography group were alive at 90 days (odds ratio, 0.89; 95% confidence interval, 0.62-1.27; P = 0.51). Sensitivity analyses suggested that only older age (P = 0.007 for interaction) and history of coronary artery disease (P = 0.009 for interaction) were associated with a higher likelihood of benefit from early invasive angiography.
Ninety percent of patients in the trial were treated with cooling in accordance with treatment guidelines. Time to reach target temperature was delayed significantly in patients assigned to the immediate angiography group, with median time to target temperature of 5.4 hours in the immediate group vs. 4.7 hours in the delayed angiography group. Life-sustaining treatment was withdrawn in approximately equal numbers of patients in each group. The authors concluded that among patients who remain comatose after resuscitation from out-of-hospital cardiac arrest without ST elevation, immediate cardiac catheterization produced no benefit vs. delayed angiography regarding survival at 90 days.
Patients who have been resuscitated from out-of-hospital cardiac arrest represent a large dilemma for clinical decision-making, with multiple competing priorities in early management. The authors of prior observational studies have reported that as much as 45% of out-of-hospital cardiac arrest patients without STEMI have acute coronary occlusion or stenosis. Further, those authors have suggested that early coronary angiography and percutaneous coronary intervention may produce a survival benefit. The authors of COACT arrived at the opposite conclusion. According to this analysis, in the average patient with resuscitated out-of-hospital cardiac arrest without STEMI, immediate angiography does not produce a concrete benefit in terms of survival at 90 days.
Why the discrepancy? The obvious initial explanation is the selection bias inherent in earlier observational studies in which patients who are presumed to have a better chance at survival are selected for early cardiac cath. While the fraction of patients with obstructive coronary disease mirrors earlier reports (at approximately two-thirds), only 5% of the total population in COACT showed acute thrombotic occlusions. Most deaths in this patient group result from neurologic complications rather than from cardiovascular sequelae. More than 60% of deaths in COACT were due to neurologic injury, which frequently led to discontinuation of treatment. The delay in time to target temperature inherent in taking patients immediately for angiography may reduce any putative benefits of this approach.
For the first time, there are randomized data to reference when presented with patients of this type. In such out-of-hospital cardiac arrest patients who are comatose and hemodynamically stable without ST elevation, the results of this study suggest that activation of the cardiac catheterization laboratory after hours is not beneficial in the average case. Thus, more time will be available to collect information about the patient that may affect decision-making in the lab. Although only 5% of patients overall exhibited an acute thrombotic lesion, percutaneous coronary intervention was performed in more than 30%. Waiting for basic labs and clinical information makes sense before committing patients to this treatment.
Keep in mind that different patient selection may have produced a different result. Patients older than 70 years of age and those with a known history of coronary disease appeared to be more likely to benefit from immediate coronary angiography. In at least two ongoing studies (the ACCESS trial and the Direct or Subacute Coronary Angiography in Out-of-hospital Cardiac Arrest trial), researchers are investigating the timing of coronary angiography after cardiac arrest. Until those studies become available, COACT provides the best available guidance.