G Model

ARTICLE IN PRESS

RESUS-7417; No. of Pages 2

Resuscitation xxx (2017) xxx–xxx

Contents lists available at ScienceDirect

Resuscitation journal homepage: www.elsevier.com/locate/resuscitation

Editorial

Emergent coronary angiography post arrest–Do observational studies provide enough evidence for strong recommendations?

International guidelines strongly recommend emergent coronary angiography (CAG) and percutaneous coronary intervention (PCI), if indicated, in patients with return of spontaneous circulation after an out-of-hospital cardiac arrest (OHCA) [1–3]. These strong recommendations apply to all patients with ST-elevation postarrest and to “selected” patients without ST-elevation, although they don’t specify how to select these patients. In patients who undergo CAG after OHCA, 80–96% have an acute coronary occlusion when presenting with ST-elevation while 24–33% of those without ST-elevation also have an acute occlusion [4]. These numbers illustrate the limited sensitivity and specificity of the post-arrest ECG in the diagnosis of acute coronary occlusions. Our knowledge and recommendations for optimal management of OHCA patients, however, are based upon the current body of evidence which consists predominantly of single-centre retrospective (and prospective) observational studies. These studies suggest better outcomes with an early invasive strategy but are likely confounded by selection bias. In this edition of Resuscitation, Staudacher and colleagues report findings from their six-year experience of managing 507 OHCA survivors without an obvious non-cardiac cause of arrest [5]. In a retrospective, observational cohort study in the Netherlands, they compared 291 patients either with or without ST-elevation who underwent CAG/PCI in ≤3 h (early invasive) with 216 patients who did not undergo CAG/PCI within 3 h. The latter group included 100 patients who had delayed CAG/PCI (mean of 69 +/− 119 h after admission) and 116 patients who did not undergo CAG. After adjustment for known prognostic variables, this study found no statistically significant association between an early invasive strategy and mortality at 30 days (29% compared to 37%, p = 0.07). The absence of significant difference persisted when the patients were divided based on whether their ECG showed ST-elevation or not. The results were robust when the authors explored the effect of CAG/PCI performed earlier (<2 h) or later (<6 h), with no significant difference in mortality. As expected, in a multi-variable regression analysis, the variables independently associated with 30-day mortality were age, cardiogenic shock and time until ROSC. Overall, these results appear to contradict the guideline recommended approach to emergent CAG in OHCA survivors. Small and moderate-sized observational studies, however, may lack power to identify differences in mortality. When examining the point estimate and confidence interval (CI) for the hazard ratio (HR) of mortality in Staudacher’s study (HR 0.69; 95% CI 0.35–1.37), it

becomes clear that, the point estimate favours benefit, but neither benefit nor harm can be excluded. Based on the GRADE framework, this outcome suffers from imprecision, and a larger sample size would be needed to have greater confidence in the point estimate. Meta-analyses statistically combine the results of several similar studies to increase the sample size and generate more precise estimates of treatment effect. Recently, in a meta-analysis of nonrandomized studies evaluating early CAG versus no or delayed CAG post arrest which included 23 studies and over 16,000 patients, Welsford et al found consistent association between early CAG and improved survival [6]. Early CAG was associated with statistically significant reductions in short-term, long-term, and neurologically intact survival when evaluating patients with and without STelevation. In subgroup analyses, the association was consistent in <2 h and <6 h subgroups, but only in patients without ST-elevation; when the three studies (559 patients) limited to patients with STelevation were pooled, it failed to show a significant association between early CAG and survival. Similarly, in another recent systematic review and meta-analysis focused on the eight studies of 2133 patients without ST-elevation, the combined data showed a statistically significant association between early CAG and shortterm, long-term, and neurologically intact survival [7]. Both of these meta-analyses, however, determined that the observational evidence resulted in a low or very-low confidence in the point estimates. A multitude of factors influence the decision to rush a patient to the cardiac catheterization laboratory emergently after return of spontaneous circulation. Adjusting for some of these is easy in retrospective studies: age, cardiogenic shock, ECG findings, and the most common comorbidities. Others are less tangible or unreliably captured in patient charts such as frailty, downtime, quality of the chest compressions, and the patients’ and families wishes. By nature, even the most rigorous observational studies on the topic will suffer from some degree of residual confounding. Maupain and colleagues derived and validated a simple post-OHCA risk stratification score that may help determine which patients would be ideal candidates for emergent CAG [8]. While no randomized controlled trials (RCTs) comparing early versus delayed CAG in patients after an OHCA are published, and so similarly we have no RCTs evaluating how to “select” patients for CAG, we eagerly await the results of seven registered RCTs. The ongoing COACT trial will include 552 patients in the Netherlands without ST-elevation with return of spontaneous cir-

https://doi.org/10.1016/j.resuscitation.2017.12.018 0300-9572/© 2017 Elsevier B.V. All rights reserved.

Please cite this article in press as: Welsford M, Belley-Côté EP. Emergent coronary angiography post arrest–Do observational studies provide enough evidence for strong recommendations? Resuscitation (2017), https://doi.org/10.1016/j.resuscitation.2017.12.018

G Model RESUS-7417; No. of Pages 2

ARTICLE IN PRESS Editorial / Resuscitation xxx (2017) xxx–xxx

2

culation after an OHCA and randomize them to CAG and PCI within 2 h versus deferral until after clarification of the neurologic prognosis [9]. The primary outcome is mortality at 90 days. The PEARL pilot trial (NCT02387398) will include 240 patients in the United States, Australia, and Slovenia without ST-elevation post arrest and evaluate the safety and efficacy of early CAG (within 120 min) versus no early CAG; the recruitment should be completed soon. Four additional registered RCTs are randomizing OHCA patients without ST-elevation to emergent angiography (generally <2 h) compared to usual care or delayed CAG (often 2–3 days): COUPE trial in Spain (NCT02641626), EMERGE trial in France (NCT02876438), TOMAHAWK trial in Germany (NCT02750462), and the ARREST trial in the United Kingdom (ISRCTN96585404). One Swedish trial (DISCO − NCT02309151) will include patients with ST-elevation but only 40 of the 120 participants will present with ST-elevation. The results of these trials should provide high quality evidence that will guide clinicians in the management of post-arrest patients without ST elevation. From the current body of observational evidence alone, the strength of the current recommendations regarding the timing of coronary angiogram after cardiac arrest appears unjustified. Guideline developers likely extrapolated data from the myocardial infarction literature to post-arrest patients with expert opinion, leading to stronger recommendations. However, the outcomes in Staudacher’s cohort suggest that these patients may behave differently. Hopefully, high quality data stemming from the ongoing RCTs should provide strong guidance for the optimal timing of CAG after cardiac arrest. References [1].Welsford M, Nikolaou NI, Beygui F, Bossaert L, Ghaemmaghami C, Nonogi H, et al. Part 5: acute Coronary syndromes: 2015 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Circulation 2015;132(16 Suppl 1):S146–76. [2].Nolan JP, Soar J, Cariou A, Cronberg T, Moulaert VRM, Deakin CD, et al. European resuscitation council and european society of intensive care medicine 2015 guidelines for post-resuscitation care. Intensive Care Med 2015;41(12):2039–56. Springer Berlin Heidelberg. [3].Callaway CW, Donnino MW, Fink EL, Geocadin RG, Golan E, Kern KB, et al. Part 8: post-Cardiac arrest care: 2015 american heart association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2015;132(18 Suppl 2):S465–82.

[4].Radsel P, Knafelj R, Kocjancic S, Noc M. Angiographic characteristics of coronary disease and postresuscitation electrocardiograms in patients with aborted cardiac arrest outside a hospital. The American Journal of Cardiology 2011;108(5):634–8. [5].Staudacher II, den Uil C, Jewbali L, van Zandvoort L, Zijlstra F, Van Mieghem N, et al. Timing of coronary angiography in survivors of out-of-hospital cardiac arrest without obvious extracardiac causes. Resuscitation 2017, in press. [6].Welsford M, Bossard M, Shortt C, Pritchard J, Natarajan MK, Belley-Côté EP. Does early angiography improve survival after out-of-Hospital cardiac arrest? a systematic review with meta-Analysis. Can J Cardiol 2017, in press. [7].Khan MS, Shah SMM, Mubashir A, Khan AR, Fatima K, Schenone AL, et al. Early coronary angiography in patients resuscitated from out of hospital cardiac arrest without ST-segment elevation: a systematic review and meta-analysis. Resuscitation 2017;121:127–34. [8].Maupain C, Bougouin W, Lamhaut L, Deye N, Diehl J-L, Geri G, et al. The CAHP (Cardiac Arrest Hospital Prognosis) score: a tool for risk stratification after outof-hospital cardiac arrest. Eur Heart J 2015;37(42):3222–8. [9].Lemkes JS, Janssens GN, Straaten HMO-V, Elbers PW, van der Hoeven NW, Tijssen JGP, et al. Coronary angiography after cardiac arrest: rationale and design of the COACT trial. Am Heart J 2016;180:39–45.

Michelle Welsford a,b,∗ Division of Emergency Medicine, McMaster University, Hamilton, Ontario, Canada b Centre for Paramedic Education & Research, Hamilton Health Sciences, Hamilton, Ontario, Canada a

Emilie P. Belley-Côté a,b Division of Cardiology, McMaster University, Hamilton, Ontario, Canada b Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada a

∗ Corresponding

author at: Centre for Paramedic Education and Research Professor and Interim Director, Division of Emergency Medicine, McMaster University 430 McNeilly Road, Unit 201, Stoney Creek, ON L8E 5E3, Canada. E-mail address: [email protected] (M. Welsford) 11 December 2017 14 December 2017

Please cite this article in press as: Welsford M, Belley-Côté EP. Emergent coronary angiography post arrest–Do observational studies provide enough evidence for strong recommendations? Resuscitation (2017), https://doi.org/10.1016/j.resuscitation.2017.12.018