Early Coronary Angiography Post-ROSC: ALS CoSTR Systematic Review

Conflict of Interest Declaration

The ILCOR Continuous Evidence Evaluation process is guided by a rigorous ILCOR Conflict of Interest policy. The following Task Force members and other authors were recused from the discussion as they declared a conflict of interest: (none applicable)

The following Task Force members and other authors declared an intellectual conflict of interest and this was acknowledged and managed by the Task Force Chairs and Conflict of Interest committees: (none applicable)

CoSTR Citation

Ian R Drennan, Nikolaos Nikolaou, Stuart Netherton, Michelle Welsford, Kevin Nation, Emilie Belley-Cote, Nazi Torabi, Laurie J. Morrison, on behalf of the International Liaison Committee on Resuscitation’ s (ILCOR) Advanced Life Support Task Force. Early Coronary Angiography Post-ROSC [Internet] Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support Task Force, 2021 April XX. Available from: http://ilcor.org

Methodological Preamble and Link to Published Systematic Review

The continuous evidence evaluation process for the production of Consensus on Science with Treatment Recommendations (CoSTR) started with a systematic review conducted by Nikolaos Nikolaou (Nikolaou N, 2019, CRD42020160152– PROSPERO citation) with involvement of clinical content experts. Evidence for adult literature was sought and considered by the Advanced Life Support Task Force.

Systematic Review

Webmaster to insert the Systematic Review citation and link to Pubmed using this format when it is available.

PICOST

This systematic review was registered with PROSPERO CRD 42020160152.

Consensus on Science

Preamble: This PICOST question was designed to address the question in the undifferentiated cohort i.e. for all ECG patterns (ST Elevation and No ST Elevation) and all initial rhythms (i.e. shockable and non-shockable). The preponderance of the observational studies address this undifferentiated cohort. The three randomized controlled trials which precipitated this systematic review included patients presenting with No ST Elevation post ROSC (two trials) and No ST Elevation post ROSC with an initial shockable rhythm (1 trial). After reviewing the evidence profile tables the ALS Task Force advised the writing group to reconfigure and present the evidence into the 3 cohorts of interest for the clinicians: 1) POST ROSC No ST Elevation and any initial rhythm 2) POST ROSC No ST Elevation and initial shockable rhythm 3) POST ROSC ST Elevation. We have included the fourth of POST ROSC all ECGS and all rhythms as well as a fifth cohort of POST ROSC all ECGs and initial shockable rhythm since this addressed the original PICOST. For each of the cohorts recommendations are based on data from randomized controlled trials if available. If no RCT data is available, we reported adjusted analyses of data from observational studies with a low to moderate risk of bias. If no adjusted analyses were reported we used unadjusted results from observational studies from low to moderate risk of bias. Data from observational studies with a serious or very serious risk of bias are included in a supplement for completeness at the request of the ALS Task Force. Table 1 includes all the characteristics for every study or trial included in this CoSTR. This data is presented by the five cohorts of interest.

POST ROSC No ST-segment Elevation on ECG and all initial rhythms

There are two RCTs that enrolled this cohort of patients (Elfwen 2019, 253 and Kern, 2020, 2002)

For the critical outcome of survival at hospital discharge we identified low certainty evidence (downgraded for serious risk of bias and serious imprecision) from a small RCT stopped early for futility (Kern, 2020, 2002) enrolling 99 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit from the use of the early coronary angiography (I) when compared with late/no angiography(C) [OR 1.33 (95% CI, 0.60 to 2.93); RR 1.08 (95% CI, 0.92 to 1.27); absolute survival difference 0.07 (95% CI, 0.07 to 0.21) or 71 more patients survived to hospital discharge (95% CI, from 119 fewer patients/1000 to 131 more patients/1000 survived with intervention)].

For the critical outcome of functional survival at hospital discharge (CPC ≤ 2) we identified low certainty evidence (downgraded for serious risk of bias and serious imprecision) from a small RCT stopped early for futility (Kern, 2020, 2002) enrolling 99 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit from the use of the early coronary angiography (I) when compared with late/no angiography(C) [OR 1.22 (95% CI, 0.56 to 2.69); RR 1.08 (95% CI, 0.92 to 1.27); absolute survival difference 0.07 (95% CI, 0.07 to 0.21) or 50 more patients (95% CI, from 142 fewer patients/1000 to 257 more patients/1000 with functional survival at hospital discharge with intervention)].

For the critical outcome of survival at 30 days we identified low certainty evidence (downgraded for serious risk of bias and serious imprecision) from a small RCT stopped early for futility (Kern, 2020, 2002) enrolling 99 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit from the use of the early coronary angiography (I) when compared with late/no angiography(C) [OR 1.44 (95% CI, 0.65 to 3.18); RR 1.20 (95% CI, 0.81 to 1.77); absolute survival difference 0.09 (95% CI, -0.10 to 0.22) or 91 more patients (95% CI, from 103 fewer patients/1000 to 275 more patients/1000 with functional survival at 30 days with intervention)].

For the critical outcome of functional survival at 30 days (CPC <2) we identified low certainty evidence (downgraded for serious risk of bias and serious imprecision) from a small RCT stopped early for futility (Kern, 2020, 2002) enrolling 99 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit from the use of the early coronary angiography (I) when compared with late/no angiography(C) [OR 1.35 (95% CI, 0.59 to 3.08); RR 1.21 (95% CI, 0.71 to 2.07); absolute survival difference 0.07 (95% CI, -0.12 to 0.25) or 68 more patients (95% CI, from 117 fewer patients/1000 to 247 more patients/1000 with functional survival at 30 days with intervention)].

For the critical outcome of survival at 180 days we identified low certainty evidence (downgraded for serious risk of bias and serious imprecision) from a small RCT stopped early for futility (Kern, 2020, 2002) enrolling 99 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit from the use of the early coronary angiography (I) when compared with late/no angiography(C) [OR 1.50 (95% CI, 0.66 to 3.40); RR 1.25 (95% CI, 0.80 to 1.96); absolute survival difference 0.10 (95% CI, -0.10 to 0.29) or 100 more patients (95% CI, from 98 fewer patients/1000 to 288 more patients/1000 with functional survival at 180 days with intervention)].

For the critical outcome of functional survival at 180 days (CPC <2) we identified low certainty evidence (downgraded for serious risk of bias and serious imprecision) from a small RCT stopped early for futility (Kern, 2020, 2002) enrolling 99 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit from the use of the early coronary angiography (I) when compared with late/no angiography(C) [OR 1.38 (95% CI, 0.58 to 3.29); RR 1.26 (95% CI, 0.68 to 2.33); absolute survival difference 0.07 (95% CI, -0.11 to 0.24) or 67 more patients (95% CI, from 111 fewer patients/1000 to 239 more patients/1000 with functional survival at 180 days with intervention)].

For the important outcome of survival at 24-h we identified very low certainty evidence (downgraded for serious risk of bias and very serious imprecision) from a pilot RCT (Elfwen 2019 253) enrolling 78 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit from the use of the early coronary angiography (I) when compared with late/no angiography(C) [OR 2.06 (95% CI, 0.48 to 8.90); RR 1.15 (95% CI, 0.78 to 1.68); absolute survival difference -0.07 (95% CI, to -0.26 to 0.12) or 71 more patients survived at 24 hours (95% CI, from 122 fewer patients/1000 to 257more patients/1000 survived with intervention)].

POST ROSC No ST-segment Elevation on ECG and shockable Initial Rhythm

There is a single clinical trial that enrolled this cohort of patients (Lemkes, 2019, 39)

For the critical outcome of survival to hospital discharge, we identified low certainty evidence (downgraded for indirectness and imprecision) from 1 RCT (Lemkes 2019 39) enrolling 538 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit from the use of early coronary angiography (I) when compared with late/no angiography (C) [OR 0.85 (95% CI, 0.60 to 1.22); RR 0.95 (95% CI, 0.84 to 1.07); absolute survival difference (ASD), -3.4% ( 95% CI, -11.4% to 4.5%) or 36 fewer patients/1000 survived with the intervention (95% CI, 119 fewer patients/1000 to 41 more patients/1000 survived with the intervention)].

For the critical outcome of survival at 90 days, we identified low certainty evidence (downgraded for indirectness and imprecision) from 1 RCT (Lemkes 2019 39) enrolling 538 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit from the use of the early coronary angiography (I) when compared with late/no angiography (C) [OR 0.89 (95% CI, 0.62 to 1.27); RR 0.96 (95% CI, 0.85 to 1.08); absolute survival difference -0.03 (95% CI -0.11 to 0.05) or 26 fewer patients/1000 survived with the intervention (95% CI, 113 fewer patients/1000 to 50 more patients/1000 survived with the intervention)].

For the critical outcome of survival with favourable neurologic outcome at ICU discharge (CPC ≤2), we identified low certainty evidence (downgraded for indirectness and imprecision) from 1 RCT (Lemkes 2019 39) enrolling 538 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit from the use of the early coronary angiography (I) when compared with late/no angiography (C) [OR 0.80 (95% CI, 0.56 to 1.14); RR 0.90 (95% CI, 0.77 to 1.06)]; absolute survival difference -0.05 (95% CI -0.14 to 0.03) or 55 fewer patients survived with the intervention (95% CI, 144 fewer patients/1000 to 32 more patients/1000 survived with the intervention)].

For the critical outcome of survival with favourable neurologic outcome at 90 days (CPC≤2) we identified low certainty evidence (downgraded for indirectness and imprecision) from 1 RCT (Lemkes 2019 39) enrolling 538 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit from the use of the early coronary angiography (I) when compared with late/no angiography [OR 0.94 (95% CI, 0.66 to 1.33); RR 0.98 (95% CI, 0.86 to 1.11); absolute survival difference -0.02 (95% CI -0.10 to 0.07) or 14 fewer patients/1000 survived with the intervention (95% CI 97 fewer patients/1000 to 60 more patients/1000 survived with the intervention)].

For the important outcome of PCI frequency, we have considered two separate analyses:

1. Intention to treat analysis (including all patients that were stratified in the intervention and control groups): We identified high certainty evidence from 1 RCT (Lemkes 2019 39) enrolling 538 patients with ROSC after out-of-hospital cardiac arrest which showed that PCI was performed more frequently in the early coronary angiography group (I) when compared with late/no angiography group [OR 1.54 (95% CI, 1.06 to 2.25); RR 1.37 (95% CI, 1.04 to 1.79); absolute difference 0.09 (95% CI, 0.01 to 0.16) or 88 more/1000 patients had PCI in the intervention group (95% CI, 11 more patients/1000 to 176 more patients/1000 had PCI in the intervention group)].
2. Per protocol analysis (including only patients that had angiography in the intervention and control groups): We identified moderate certainty evidence (downgraded for serious imprecision) from 1 RCT (Lemkes 2019 39) enrolling 437 patients with ROSC after out-of-hospital cardiac arrest which showed that PCI was performed with equal frequency in the early coronary angiography group (I) when compared with late/no angiography group [OR 0.87 (95% CI, 0.58 to 1.30); RR 0.91 (95% CI, 0.71 to 1.18); absolute difference -0.03 (95% CI, -0.12 to 0.06) or 32 fewer patients/1000 had PCI in the intervention group (95% CI, 116 fewer patients/1000 to 63 more patients/1000 had PCI in the intervention group)].

For the important outcome of CABG only intention to treat analysis was performed.

We identified moderate certainty evidence (downgraded for serious imprecision) from 1 RCT (Lemkes 2019 39) enrolling 538 patients with ROSC after out-of-hospital cardiac arrest which showed that CABG was performed with equal frequency in the early coronary angiography group (I) when compared with late/no angiography group [OR 0.87 (95% CI 0.45 to 1.67); RR 0.88 (0.48 to 1.60); absolute survival difference -0.01 (95% CI -0.06 to 0.04) or 10 fewer patients/1000 with CABG in the intervention group (95% CI from 46 fewer to 157 more patients/1000 with CABG in the intervention group)].

For the critical outcome of survival with favourable neurologic outcome at hospital discharge (CPC=1) we identified low certainty evidence (downgraded for very serious risk of bias) from one observational study (Vyas 2015 1) including 4029 patients with ROSC after out-of-hospital cardiac arrest with shockable initial rhythm which showed benefit with early coronary angiography (I) when compared with late/no angiography (C) [adjusted OR 1.47 (95% CI, 1.26 to 1.72); RR 1.18 (95% CI 1.1 to 1.25); absolute survival difference 0.19 (95% CI 0.16 to 0.22) or 94 more patients/1000 survived with favourable neurologic outcome in the early CAG group (95% CI from 57 more patients/1000 to 131 more patients/1000 survived with favourable neurologic outcome in the early CAG group].

POST ROSC With ST-segment Elevation on ECG

For the critical outcome of survival at hospital discharge we identified very-low certainty evidence from one study (Garcia 2016) of 112 patients which reported adjusted effect estimates for early coronary angiography compared to late/no coronary angiography for patients with ROSC after out-of-hospital cardiac arrest. The study found no effect with early angiography [OR 1.89 (95% CI 0.48 to 7.40)].

For the critical outcome of favourable neurologic outcome at hospital discharge (CPC≤2) ) we identified very low certainty evidence) from one study (Garcia 2016) of 112 patients which reported adjusted effect estimates for early coronary angiography compared to late/no coronary angiography for patients with ROSC after out-of-hospital cardiac arrest. The study found no effect with early angiography [OR 1.12 (95% CI 0.3 to 4.19)].

POST ROSC all ECGs (Undifferentiated)

For the critical outcome of survival at 30 days, we identified low certainty evidence (downgraded for moderate risk of bias) from 1 study (Geri 2015 e002303) enrolling 1722 patients with ROSC after out-of-hospital cardiac arrest which showed benefit from the use of early coronary angiography (I) when compared with late/no angiography (C) [OR 1.43 (95% CI, 1.12 to 1.83), 64 patients more /1000 survived with the intervention (95% CI, 19 more patients/1000 to 116 more patients/1000 survived with the intervention)].

For the critical outcome of survival at 1-3 years, we identified very low certainty evidence (downgraded for very serious ROB and serious imprecision) from 1 non-RCT (Geri 2015 e002303) enrolling 1722 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit from the use of the early coronary angiography (I) when compared with late/no angiography (C) [adjusted OR 1.79 (95% CI, 0.93 to 3.45); RR 1.63 (95% CI 0.94 to 2.67); absolute survival difference 0.16 (95% CI 0.13 to 0.20) or 77 more patients/1000 survived with the intervention (95% CI, 8 fewer patients/1000 to 201 more patients/1000 survived with the intervention)].

For the critical outcome of survival with favourable neurologic outcome at discharge (all different neurological outcomes) we identified very-low certainty evidence from three observational studies (Calloway 2014, Tomte 2011, Vyas 2015) enrolling 8124 patients which reported adjusted effect estimates for early coronary angiography compared to late/no angiography for patients with ROSC after out-of-hospital cardiac arrest which identified a benefit of early angiography [OR 1.93 (95% CI 1.20 to 3.10)].

For the critical outcome of survival with favourable neurologic outcome at 3-6 months (CPC ≤2) we identified very-low certainty evidence from one observational study (Dankiewicz 2015) of 544 patients which reported adjusted effect estimates for early coronary angiography compared to late/no angiography for patients with ROSC after out-of-hospital cardiac arrest which identified no effect of early angiography [OR 0.92 (95% CI 0.69 to 1.18)).

For the important outcome of successful PCI we have considered two separate analyses:

1. Intention to treat analysis (including all patients in the intervention and control groups):

We identified very-low certainty evidence (downgraded for very serious ROB, serious inconsistency and publication bias strongly suspected; upgraded for strong association) from 3 non-RCTS (Bro-Jeppesen 2012 291, Dankiewicz 2015 856, Jentzer 2018 15) including 1117 patients with ROSC after out-of-hospital cardiac arrest which showed higher frequency of successful PCI in the intervention group when compared to the control group [OR 6.21 (95% CI, 4.45 to 8.67); RR 4.08 (95% CI, 3.09 to 5.40); absolute risk difference [ARD] 0.31 (95% CI 0.26,0.35) or 308 more patients/1000 had successful PCI in the intervention group (95% CI, 260 more patients/1000 to 354 more patients/1000 in the intervention group)].

1. Per-protocol analysis: including only patients that had angiography in the intervention and control groups. We identified very low quality evidence (downgraded for very serious ROB, serious imprecision and publication bias strongly suspected) from 3 non-RCTS (Bro-Jeppesen 2012 291, Dankiewicz 2015 856, Jentzer 2018 15) including 437 patients with ROSC after out-of-hospital cardiac arrest which showed no difference in the frequency of successful PCI in the intervention group when compared to the control group [OR 1.24 (95% CI, 0.49 to 3.13); RR 0.91 (95% CI, 0.71 to 1.18), absolute risk difference (ARD) -0.03 (95% CI, -0.12 to 0.06) or 19 more successful PCI in the intervention group (95% CI, from 90 fewer patients/1000 with successful PCI to 70 more patients/1000 with successful PCI in the intervention group)].

POST ROSC all ECGs (undifferentiated) with initial Shockable Rhythm

For the critical outcome of survival with favourable neurologic outcome at hospital discharge (CPC =1) we identified very-low certainty evidence from one observational study (Vyas 2015) of 4029 patients which reported adjusted effect estimates for early coronary angiography compared to late/no angiography for patients with ROSC after out-of-hospital cardiac arrest which identified benefit with early angiography [OR 1.47 (95% CI 1.36 to 1.72)].

Adverse Events by Cohort

POST ROSC No ST-segment Elevation on ECG and all initial rhythms

Brain damage

For the important outcome subarachnoid hemorrhage we identified very-low certainty evidence (downgraded for very serious risk of bias; serious indirectness; very serious imprecision) from 1 pilot RCT (Elfwen 2019 253) enrolling 78 patients with ROSC after out-of-hospital cardiac arrest which showed no difference with early coronary angiography (I) when compared with late/no angiography (C) [OR 0.34 (95 CI, 0.01 to 8.66); RR 0.35 (95%CI, 0.01 to 8.35); Absolute risk difference -0.03 (95% CI -0.52 to 0.47) or 16 fewer patients/1000 (95% CI from 25 fewer to 157 more subarachnoid haemorrhages /1000 patients)].

Recurrent Cardiac Arrest

For the important outcome of recurrent cardiac arrest (ventricular arrhythmias, VT/VF) we identified very-low certainty evidence (downgraded for serious risk of bias, serious indirectness, and very serious imprecision) from 1 pilot RCT (Elfwen 2019 253) including 78 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit with early coronary angiography (I) in comparison to late/no angiography (C) [OR 0.51 (95% CI, 0.04 to 5.91). RR 0.53 (95% CI, 0.05 to 5.57); absolute risk difference -0.02 (95% CI, -0.38 to 0.33) or 24 fewer arrhythmias with early CAG (95% CI, from 48 arrhythmias fewer to 187 more /1000 patients with intervention). We also identified very-low certainty evidence (downgraded for serious risk of bias, serious indirectness, and very serious imprecision) from 1 RCT (Kern 2020, 2002) including 99 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit with early coronary angiography (I) compared to late/no angiography (C) [OR 1.02 (95% CI, 0.20 to 5.33), RR 1.02 (95% CI 0.22, 4.81); absolute risk difference 0.001 (95% CI -0.11 to 0.11) or 1 more rearrest with early CAG (95% CI, from 109 fewer rearrest to 112 more/1000 patients with intervention)]

Arrhythmias

For the important outcome of bradyarrhythmias requiring pacemaker we identified very-low certainty evidence (downgraded for serious risk of bias, serious indirectness, and very serious imprecision) from one pilot RCT (Elfwen 219 253) including 78 patients with ROSC after out-of-hospital cardiac arrest which showed no difference with early coronary angiography (I) in comparison to late/no angiography (C) [OR 0.34 (95% CI 0.01 to 8.66); RR 0.35 (95% CI 0.01 to 0.35); absolute risk difference -0.03 (-0.09 to 0.04) or 16 fewer patients /1000 requiring pacemaker in the early CAG group (95% CI from 25 fewer patients to 157 more patients / 1000 requiring pacemaker in the early CAG group)].

Pneumonia

We identified very-low certainty evidence (downgraded for serious risk of bias, serious indirectness, and very serious imprecision) from 1 RCT (Kern 2020, 2002) including 99 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit with early coronary angiography (I) compared to late/no angiography (C) [OR 1.02 (95% CI, 0.24 to 4.34), RR 1.02 (95% CI 0.27, 3.85); absolute risk difference 0.002 (95% CI -0.12 to 0.12) or 2 more rearrest with early CAG (95% CI, from 117 fewer rearrest to 122 more/1000 patients with intervention)]

Bleeding

We identified very-low certainty evidence (downgraded for serious risk of bias, serious indirectness, and very serious imprecision) from 1 RCT (Kern 2020, 2002) including 99 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit with early coronary angiography (I) compared to late/no angiography (C). There were 0 (0.0%) cases of bleeding in the control group and 2 (4.1%) in the intervention group for an absolute risk difference of 0.04 (95% CI -0.04 to 0.14) or 41 more patients with early CAG (95% CI from 36 fewer to 137 more).

Acute Worsening Renal Failure

We identified very-low certainty evidence (downgraded for serious risk of bias, serious indirectness, and very serious imprecision) from 1 RCT (Kern 2020, 2002) including 99 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit with early coronary angiography (I) compared to late/no angiography (C) [OR 0.50 (95% CI, 0.04 to 5.70), RR 0.51 (95% CI 0.05, 5.45); absolute risk difference -0.02 (95% CI -0.12 to 0.07) or 20 fewer with acute renal failure with early CAG (95% CI, from 116 fewer rearrest to 72 more/1000 patients with intervention)]

POST ROSC No ST-segment Elevation on ECG and initial shockable rhythm

Recurrent Cardiac Arrest

For the important outcome of recurrent cardiac arrest (recurrence of VT resulting in defibrillation or electrical cardioversion) we identified low certainty evidence (downgraded for serious indirectness and serious imprecision) from 1 RCT (Lemkes 2019 39) including 552 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit with early coronary angiography (I) in comparison to late/no angiography (C) [OR 1.30 (95% CI 0.66 to 2.54); RR 1.27 (95% CI, 0.68 to 2.39); Absolute risk reduction 0.02 (95% CI -0.34 to 0.37) or 17 more strokes /ICH /1000 patients (95% CI, from 20 strokes/ICH fewer to 80 more /1000 patients with early angiography)].

Bleeding

For the important outcome of bleeding (TIMI major bleeding), we identified low certainty evidence (downgraded for serious indirectness and serious imprecision) from one RCT (Lemkes 2019 39) including 538 patients with ROSC after out-of-hospital cardiac arrest which showed no difference with early coronary angiography (I) in comparison to late/no angiography (C) [OR 0.51 (95% CI, 0.20 to 1.30); RR 0.52 (95% CI 0.21 to 1.29); absolute risk difference -0.02 (-0.06 to 0.009) or 23 patients /1000 fewer with major bleeding in the early CAG group (95% CI from 39 fewer patients/1000 to 14 more patients/1000 with major bleeding in the early CAG group)]

Renal Replacement Therapy / Acute Kidney Injury

For the important outcome of renal replacement therapy we identified low certainty evidence (downgraded for serious indirectness and serious imprecision) from one RCT (Lemkes 2019 39) including 538 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit with early coronary angiography (I) in comparison to late/no angiography (C)[OR 0.72 (95% CI 0.29 to 1.80); RR 0.73 (95% CI 0.30 to 1.79); absolute risk difference -0.01 (95% CI -0.04 to 0.02) or 11 fewer patients /1000 requiring RRT in the early CAG group (95% CI from 29 fewer patients/1000 to 31 more patients/1000 requiring RRT in the early CAG group)].

Acute Renal Failure

For the important outcome of acute renal failure we identified low certainty evidence (downgraded for serious indirectness and serious imprecision) from one RCT (Lemkes 2019 39) including 538 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit with early coronary angiography (I) in comparison to late/no angiography (C) [OR 0.88 (95% CI 0.50 to 1.54); RR 0.89 (95% CI 0.54 to 1.47); absolute risk difference -0.01 (95%CI -0.07 to 0.04) or 13 fewer patients/ 1000 with renal failure in the early CAG group (95% CI from 56 fewer patients/1000 to 53 more patients /1000 with acute renal failure in the early CAG group)].

Shock

For the important outcome of shock we identified very-low certainty of evidence (downgraded for serious risk of bias, serious indirectness, serious imprecision) from one RCT (Lemkes 2019 39) including 538 patients with ROSC after out-of-hospital cardiac arrest. Shock was defined as lowest mean arterial pressure at day 1, 2, and 3 or lactate level at day 1, 2, and 3. No difference was found in lowest mean arterial pressure at day one [mean difference 0.68 (95% CI −1.46 to 2.82)], lowest mean arterial pressure at day two [mean difference −0.52 (95% CI −2.63 to 1.58)] or lowest mean arterial pressure at day three (mean difference −0.94 (95% CI −3.85 to 1.96)]. No significant difference in the ratios of geometric means at day one, 1.09 (95% CI 0.96 to 1.23), day two, 1.04 (95% CI 0.92 to 1.17) and day three, 1.00 (95% CI 0.90 to 1.11).

POST ROSC all ECGs (undifferentiated)

Brain Damage

For the important outcome composite end point of stroke or ICH we identified very-low certainty evidence (downgraded for very serious ROB; serous imprecision) from 1 non-RCT [Callaway 2014 657] including 3981 patients with ROSC after out-of-hospital arrest which showed no difference with early coronary angiography (I) when compared with late/no angiography (C) [OR 0.67 (95% CI, 0.41 to 1.10); RR 0.68 (95% CI 0.41 to 1,1]; Absolute risk difference -0.001 (95% CI -0.02 to 0.001) or 12 fewer patients /1000 with stroke or ICH in the early CAG group (95% CI from 21 fewer patients/1000 to 3 more patients/1000 with stroke or ICH in the early CAG group).

Recurrent Cardiac Arrest

For the important outcome of recurrent cardiac arrest we identified very-low certainty evidence (downgraded for very serious risk of bias, serious indirectness, and serious imprecision) from one non-RCT (Callaway 2014 657) including 3981 patients with ROSC after out-of-hospital cardiac arrest which showed no benefit with early coronary angiography (I) in comparison to late/no angiography (C) [OR 1.35 (95% CI, 0.94 to 1.92); RR 1.33 (95% CI 0.95 to 1.86); absolute risk difference 0.01 (95% CI -0.004 to 0.03) or 14 more patients/1000 had recurrent arrest with early CAG (95% CI from 2 fewer patients/1000 to 35 more patients/1000 had recurrent arrest with early CAG)].

Sepsis

For the important outcome of sepsis we identified very-low certainty evidence (downgraded for very serious risk of bias, serious indirectness, and serious imprecision) from one non-RCT (Callaway 2014 657) including 3981 patients with ROSC after out-of-hospital cardiac arrest which showed no difference with early coronary angiography (I) in comparison to late/no angiography (C) [OR 0.81 (95% CI, 0.55 to 1.20); RR 0.81 (96% CI 0.56 to 1.19); absolute risk difference -0.009 (95% CI -0.03 to 0.007) or 9 fewer patients/1000 with sepsis (95% CI 22 fewer patients/1000 to 10 more patients/1000 with sepsis in the early CAG group)].

For the important outcome of sepsis, we identified very-low certainty evidence (downgraded for very serious risk of bias, very serious imprecision) from one non-RCT (Casella 2015 579) including 141 patients with ROSC after out-of-hospital cardiac arrest which showed no difference with early coronary angiography (I) in comparison to late/no angiography (C) [OR 1.92 (95% CI, 0.80 to 4.63); RR 1.64 (95% CI 0.82 to 3.30); absolute risk difference 0.12 (95% CI -0.03 to 0.26) or 117 more patients/1000 with sepsis (95% CI from 31 fewer to 325 more patients/1000 with sepsis in the early CAG group)].

Pneumonia

For the important outcome of pneumonia, we identified very-low certainty evidence (downgraded for very serious risk of bias, serious indirectness, and serious imprecision) from 1 non-RCT (Callaway 2014 657) including 3981 patients which showed no difference with early coronary angiography (I) in comparison to late/no angiography (C) [OR 1.22 (95% CI, 0.98 to 1.52); RR 1.18 (95% CI 0.97 to 1.43); absolute risk difference 0.03 (95% CI -0.003 to 0.05) or 25 more patients/1000 with pneumonia (95% CI from 2 fewer patients/1000 to 57 more patients /1000 with pneumonia in the early CAG group)].

Bleeding

For the important outcome of bleeding (hemorrhage) we identified very-low certainty evidence (downgraded for very serious risk of bias and very serious imprecision) from one non-RCT (Casella 2015, 579) including 278 patients with ROSC after out-of-hospital cardiac arrest which showed no difference with early coronary angiography (I) in comparison to late/no angiography (C) [OR2.84 (95% CI 0.33 to 24.29); RR 2.72 (95% CI 0.34 to 21.93); absolute risk difference 0.04 (95% CI -0.03 to 0.10) OR 39 more patients/1000 with bleeding in the early CAG group (95% CI from 15 fewer patients/1000 to 338 more patients/1000 with bleeding with early CAG)].

For the important outcome of bleeding (unclear definition) we identified very-low certainty evidence (downgraded for very serious risk of bias and very serious imprecision) from one non-RCT (Callaway 2014 657) including 3981 patients with ROSC after out-of-hospital cardiac arrest which showed increased bleeding with early coronary angiography (I) in comparison to late/no angiography (C) [OR 1.61 (95% CI, 1.04 to 2.48); RR 1.58 (95 % CI 1.04 to 2.41); absolute risk difference 0.01 (95% CI -0.0006 to 0.03) or 14 more patients/1000 with bleeding in the early CAG group (95% CI from 1 more patient/1000 to 33 more patients/1000 with bleeding in the early CAG group].

For the important outcome of any bleeding we identified very-low certainty evidence (downgraded for very serious risk of bias and serious imprecision) from one non-RCT (Dankiewicz 2015 856) including 544 patients with ROSC after out-of-hospital cardiac arrest which showed increased rates of any bleeding with early coronary angiography (I) in comparison to late/no angiography (C) [1.80 (95% CI, 1.15 to 2.81); RR 1.62 (95% CI 1.12 to 2.35); absolute risk difference 0.09 (0.02 to 0.15) or 171 more patients/1000 with any bleeding in the early CAG group (95% CI from 17 more patients /1000 to 145 more patients/1000 with any bleeding in the early CAG group)], but no differences in uncontrolled bleeding, bleeding in a critical organ as well as gastrointestinal, tracheal, oral, genital and nasal bleeding. The difference was mostly accounted by bleeding at insertion sites [OR 2.57 (95% CI, 1.26 to 5.23; RR 2.41 (95% CI 1.24 to 4.71); absolute risk difference 0.06 (95% CI 0.01 to 0.10) or 58 more patients /1000 with bleedings at insertion sites (95% CI from 10 more patients/ 1000 to 142 more patients/1000 with bleedings at insertion sites in the early CAG group)].

Treatment Recommendations

When coronary angiography is considered for comatose post-arrest patients without ST elevation, we suggest that either an early or a delayed approach for angiography is reasonable. (weak recommendation, low certainty of evidence)

We suggest early coronary angiography in comatose post-cardiac arrest patients with ST segment elevation. (good practice statement)

Justification and Evidence to Decision Framework Highlights

Without ST-segment elevation

In making the above recommendations, the taskforce weighed the fact that we did not find sufficient evidence to demonstrate improved outcomes with early angiography for post cardiac arrest patients without ST-segment elevation regardless of presenting cardiac arrest rhythm (shockable or non-shockable). Patients in cardiogenic shock post arrest were excluded from all studies and there is unlikely to ever be sufficient clinical equipoise to support a randomized trial of delayed intervention in the shock cohort. There may be subgroups of patients without ST-segment elevation with high-risk features that would benefit from earlier coronary angiography.

Importantly this review examined the timing of coronary angiography if it was done, and did not compare to no coronary angiography. It may be that survival and functional survival may not be the right outcomes to measure harm or benefit from an intervention that adjusts the timing of PCI in post arrest patients. We know that the majority of patients admitted to hospital after cardiac arrest do not die from cardiac complications and most die as a result of neurologic injury. There are no significant differences in adverse event rates with either time interval.

With ST-segment elevation

For comatose patients with ST segment elevation there is no randomized clinical evidence for the timing of coronary angiography. The Task Force acknowledges that early coronary angiography, and percutaneous intervention if indicated, is the current standard of care for patients with STEMI who did not have a cardiac arrest. We found no evidence to change this approach in patients with ST segment elevation following cardiac arrest.

Knowledge Gaps

• Future trials should consistently define what are the comparable time intervals to treatment for early compared to late angiography and PCI.
• Whether early coronary angiography improves survival/survival with favorable neuro outcome for post-arrest patients with ST elevation
• Whether angiography, compared to no angiography, improves outcomes in post-arrest patients
• Whether angiography and PCI may improve outcomes in the no ST elevation cohort who present in shock
• No studies identified evaluated this question for cardiac arrest in the in-hospital setting.
• No RCTs compared angiography and PCI vs thrombolysis and early vs late time to treatment interval.
• Most randomized trials have focused on short term survival and functional outcomes so data on longer term outcomes is relatively more limited.
• Relatively few studies examining health related quality of life (HRQoL) outcomes
• There may be newer or alternative endpoints such as functional or biochemical measures that may show a benefit with timing of coronary angiography in cardiac arrest patients

Attachments:

Et D-Framework_STEMI

Et D-Framework_No-STEMI

Co STR-supplement

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