Article
Lemkes JS, Janssens GN, van der Hoeven NW, et al. Coronary Angiography after Cardiac Arrest without ST-Segment Elevation. N Engl J Med. 2019;380:1397-407.
OBJECTIVE
To determine if immediate coronary angiography in the setting of ROSC without STEMI changes on ECG following out of hospital cardiac arrest confers superiority in 90 day mortality compared to delayed coronary angiography.
BACKGROUND
Out of hospital cardiac arrest is cited as a leading cause of death in Europe and the U.S. Of note and concern, mortality as high as 40% has been reported among patients with successful ROSC following out-of-hospital cardiac arrest associated with shockable rhythms (VF, pulseless ventricular tachycardia [pVT]). Post-resuscitation care recommendations include treatment of the inciting cause of cardiac arrest as well as vital-organ support and targeted temperature management. However, appropriate clinical guidance of treatment in the immediate post-ROSC period is often challenged by the lack of a definitive diagnosis and uncertainty over the inciting cause of the arrest event. In Europe and the U.S., immediate coronary angiography in patients with STEMI and cardiac arrest is recommended by current guidelines. International guidelines recommend emergency coronary angiography in select patients following out-of-hospital cardiac arrest, even in the absence of STEMI; for this patient group, observational studies demonstrate conflicting outcomes of immediate coronary angiography, and data from randomized studies is sparse.
DESIGN
- Investigator-initiated, prospective, randomized controlled, open-label, multicenter clinical trial
- Intention to treat (ITT), pre-defined subgroup, sensitivity analyses
Inclusion Criterion
- Age > 18 Years
- Glasgow Coma Score < 8 with ROSC following out of hospital cardiac arrest
- Initial arrest rhythm is shockable (VF or pVT)
Exclusion Criterion
- ED ECG demonstrating STEMI (including new left bundle branch block [LBBB] or isolated ST depression in V1-V3 due to true posterior myocardial infarction)
- Hemodynamic instability not responsive to medical therapy (systolic blood pressure < 90 mmHg for >30 minutes at time of screening)
- Non-coronary cause for arrest
- Known severe renal dysfunction (GFR < 30 ml/min)
- Pregnancy (obvious or suspected)
- Intracranial bleeding (suspected or confirmed)
- Acute stroke (suspected or confirmed)
- Patients with Do Not Resuscitate order
- Known pre-arrest Cerebral Performance Category 3 or 4
- Time lapse >4 hours between ROSC and screening for study
- Refractory ventricular tachycardia
- Known inability to complete 90 day follow-up
Randomization
- Between January 2015 and July 2018, 552 patients in 19 sites in 15 cities in the Netherlands underwent randomization
- Patients screened for trial eligibility in ED
- Eligible patients randomly assigned in 1:1 ratio to immediate or delayed angiography
- Final analysis includes 273 patients randomized to immediate angiography and 265 patients randomized to delayed angiography
552 patients were enrolled at 19 participating sites:
- 14 (2.54%) withdrew
- 0% of survivors lost to follow-up
- 538 patients included in final analysis
Outcomes Measured
Primary: Survival at 90 days
Secondary
- Survival at 90 days with good cerebral performance or mild/moderate disability
- Myocardial injury (quantified on basis of troponin levels, increased CK and CKMB levels)
- Acute kidney injury
- Need for renal replacement therapy (RRT)
- Time to target temperature
- Duration of catecholamine or inotropic therapy
- Neurologic status at time of discharge from intensive care unit
- Markers of shock
- Recurrence of VT requiring defibrillation or electrical cardioversion
- Duration of mechanical ventilation
- Major Bleeding (per Thrombolysis in Myocardial Infarction [TIMI] criteria)
KEY RESULTS
Primary: Survival to 90 days for immediate v. delayed coronary angiography was, respectively, 64.5% v. 67.2%, (odds ratio, 0.89; 95% confidence interval [CI] 0.62 to 1.27; p = 0.51).
Secondary
- Median time to target temperature for immediate v. delayed coronary angiography was, respectively, 5.4 hours v. 4.7 hours (ratio of geometric means, 1.19; 95% CI, 1.04 to 1.36).
- No significant differences between immediate v. delayed coronary angiography groups were found for the remaining secondary endpoints.
STUDY STRENGTHS
- Randomized, controlled, multicenter trial
- ITT analysis, sensitivity analysis
- Survival is a patient-centered outcome
- Primary outcome measure of 90-day mortality is a robust endpoint
STUDY LIMITATIONS
- Data regarding patient screening obtained only in final phase of trial
- Small population analyzed (n= 538) may not yield results generalizable to an at-large population
- Trial not blinded; physicians responsible for care of patients aware of randomizations which may have influenced subsequent treatment
- Due to exclusion criterion, results of study cannot be applied to patients with STEMI, shock, or severe renal dysfunction. Other important patient populations for whom the study results cannot be applied include those with advanced cerebral dysfunction, patients with intracranial hemorrhage or acute stroke, and pregnant patients.
- Though 64.5% of patients randomized to immediate angiography determined to have coronary artery disease (CAD), majority were diagnosed with stable disease; percuntaneous coronary intervention (PCI) is associated with improved outcomes in patients with acute thrombotic coronary occlusion (STEMI) but not those with stable CAD.
AUTHORS’ CONCLUSIONS
Immediate angiography following ROSC amongst patients with out of hospital cardiac arrest with an initially shockable rhythm and absence of ST-segment elevations on ECG is not better than a strategy of delayed angiography with respect to overall survival at 90 days.
DISCUSSION
The implications of the results of this study are relevant to the scope of practice for emergency medicine physicians. The decision to promptly involve an interventional cardiologist in the care of patients like those examined in this study should be driven by the perceived utility of coronary angiography in guiding the management of the patient as well as implications for short- and long-term survival. While this study demonstrates that immediate coronary angiography is not superior to delayed angiography with respect to 90-day survival, it should also be noted that across both groups studied, less than half of patients were found to have intervenable coronary disease – perhaps obviating the role of immediate coronary angiography in the absence of STEMI. In addition, angiography revealed no clinically significant coronary artery disease in greater than one third of patients in both groups. Although 64.5% of patients randomized to immediate angiography were determined to have CAD, the majority of these patients were diagnosed with stable disease; PCI is associated with improved outcomes in patients with acute thrombotic coronary occlusion (STEMI) but not those with stable CAD.
Although this study fails to prove that immediate angiography is superior to delayed angiography with respect to survival at 90 days, considerations for practice may still be derived for the seasoned emergency medicine physician. The lack of superiority in immediate angiography compared with delayed angiography as evidenced in this study should not by itself obviate the consideration of urgent coronary intervention. Rather, it may be reasonable to consider an approach where patients are stratified by history, known risk factors for CAD and the presence of CAD equivalents (diabetes mellitus, peripheral arterial disease) if such information is available.
Though this study may appropriately be applied to guide clinical decision making in the Netherlands with the additional caveats discussed above, the external validity of this study to the U.S. population is uncertain given differences in the prevalence of cardiovascular disease in the Netherlands as well as that of CVD co-morbidities such as DM and obesity. Similarly designed studies investigating this question in a larger patient population should be undertaken in the U.S. to determine the validity of study outcomes in our population and to inform definitive clinical guidelines for post-resuscitation care amongst cardiac arrest patients following ROSC without ST-segment elevations on ECG.