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, Resuscitation, 2021 Apr 7: 163: 28-48. doi: 10.1016) with involvement of clinical content experts. Evidence for adult literature was sought and considered by the Advanced Life Support Task Force and a new CoSTR was generated for 2021. In light of the task force being aware of a new RCT on this topic, the decision was made to re-run the search utilized for the 2021 CoSTR, restricting the search to only RCTs published since the prior search was run.

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

The CoSTR text below, much of which appeared in 2021, has been updated with information from the single additional RCT (Desch 2021 2544) identified in that search as well as additional long-term outcomes published from a previously included RCT (Lemkes 2020 1358). Observational studies were not included in this updated search. Additionally, some outcomes for which observational data were previously reported now have sufficient RCT data that the observational results have been removed.

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 addresses 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 a fourth cohort of interest defined as POST ROSC all ECGS and all rhythms. Each of the cohort recommendations are based on data from randomized controlled trials if available. If no RCT data was available we reported adjusted analyses of data from observational studies published prior to 2021 with a low to moderate Risk of Bias (ROB). If no adjusted analyses were reported we used unadjusted results from observational studies from low to moderate ROB. This data is presented by the four cohorts of interest.

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

There were three RCTs that enrolled this cohort of patients (Elfwen 2019 253, Kern 2020 2002, Desch 2021 2544)

For the critical outcome of functional survival at hospital discharge (CPC ≤ 2) we identified low certainty evidence (downgraded for serious ROB 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 statistically significant difference with the use of early coronary angiography (I) when compared with late/no angiography (C) [OR 1.22 (95% CI, 0.56 to 2.69); RR 1.11 (95% CI, 0.74 to 1.67); absolute survival difference 0.05 (95% CI,- 0.14 to 0.24) or 50 more patients (95% CI, from 142 fewer patients/1000 to 237 more patients/1000 with functional survival at hospital discharge (CPC ≤ 2) after early coronary angiography)].

For the critical outcome of functional survival at 30 days (CPC <2) we identified low certainty evidence (downgraded for serious ROB and serious imprecision) from two RCTs (Desch 2021 2544; Kern 2020 2002) enrolling 629 patients with ROSC after out-of-hospital cardiac arrest which showed no statistically significant difference with the use of early coronary angiography (I) when compared with late/no angiography (C) [OR 0.88 (95% CI, 0.51 to 1.52); RR 0.92 (95% CI, 0.66 to 1.29); absolute survival difference -0.03 (95% CI,-0.15 to 0.10) or 30 fewer patients/1000 had functional survival (CPC <2) at 30 days (95% CI, from 146 fewer patients/1000 to 103 more patients/1000 had functional survival (CPC <2) at 30 days after early coronary angiography)].

For the critical outcome of functional survival at 180 days (CPC <2) we identified low certainty evidence (downgraded for serious ROB 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 statistically significant difference with the use of 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 (CPC <2) at 180 days after early coronary angiography)].

For the critical outcome of survival at hospital discharge we identified low certainty evidence (downgraded for serious ROB 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 statistically significant difference with the use of early coronary angiography (I) when compared with late/no angiography (C) [OR 1.33 (95% CI, 0.60 to 2.93); RR 1.15 (95% CI, 0.78 to 1.68); absolute survival difference 0.07 (95% CI, -0.12 to 0.26) or 71 more patients survived to hospital discharge (95% CI, from 122 fewer patients/1000 to 257 more patients/1000 survived to hospital discharge after early coronary angiography)].

For the critical outcome of survival at 30 days we identified low certainty evidence (downgraded for very serious imprecision) from two RCTs (Desch 2021 2544; Kern 2020 2002) enrolling 629 patients with ROSC after out-of-hospital cardiac arrest which showed no statistically significant difference with the use of early coronary angiography (I) when compared with late/no angiography (C) [OR 0.93 (95% CI, 0.49 to 1.76); RR 0.96 (95% CI, 0.70 to 1.33); absolute survival difference -0.02 (95% CI, -0.18 to 0.14) or 18 fewer patients/1000 survived at 30 days (95% CI, from 174 fewer patients/1000 to 135 more patients/1000 survived at 30 days after early coronary angiography)].

For the critical outcome of survival at 180 days we identified low certainty evidence (downgraded for serious ROB 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 statistically significant difference with the use of 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 /1000 (95% CI, from 98 fewer patients/1000 to 288 more patients/1000 survived at 180 days after early coronary angiography)].

For the important outcome of survival at 24-h we identified very-low certainty evidence (downgraded for serious ROB 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 statistically significant difference with the use of early coronary angiography (I) when compared with late/no angiography (C) [OR 2.06 (95% CI, 0.48 to 8.90); RR 1.08 (95% CI, 0.92 to 1.27); absolute survival difference 0.07 (95% CI, to -0.08 to 0.22) or 71 more patients/1000 survived at 24 hours (95% CI, from 80 fewer patients/1000 to 221 more patients/1000 survived at 24-h after early coronary angiography)].

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

1. Intention to treat analysis (including all patients who were stratified in the intervention and control groups): we identified high certainty evidence from two RCTs (Desch 2021 2544; Kern 2020 2002) enrolling 629 patients with ROSC after out-of-hospital cardiac arrest which showed that PCI was performed more frequently with early coronary angiography (I) when compared with late/no angiography (C) [OR 1.57 (95% CI, 1.11 to 2.21); RR 1.37 (95% CI, 1.07 to 1.74); absolute difference 0.09 (95% CI, 0.02 to 0.16) or 94 more patients/1000 had PCI (95% CI, from 20 more patients/1000 to 174 more patients/1000 had PCI with early coronary angiography)].

2. Per protocol analysis (including only patients who had angiography in the intervention and control groups): we identified moderate certainty evidence from two RCTs (Desch 2021 2544; Kern 2020 2002) enrolling 485 patients with ROSC after out-of-hospital cardiac arrest which showed no statistically significant difference in PCI frequency with early coronary angiography (I) when compared with late/no angiography (C) [OR 0.77 (95% CI, 0.53 to 1.12);RR 0.86 (95% CI, 0.68 to 1.07); absolute difference -0.06 (95% CI, -0.15 to 0.03) or 62 fewer patients/1000 had PCI (95% CI, from 143 fewer patients/1000 to 28 more patients/1000 had PCI with early coronary angiography)].

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

There was a single randomized controlled trial that enrolled this cohort of patients (Lemkes 2019 39; Lemkes 2020 1358). A second RCT (Desch 2021) included a subgroup analysis of patients who presented with an initial shockable rhythm.

For the critical outcome of functional survival at ICU discharge (CPC ≤2), we identified low certainty evidence (downgraded for indirectness and imprecision) from one RCT (Lemkes 2019 39) enrolling 538 patients with ROSC after out-of-hospital cardiac arrest which showed no statistically significant difference with the use of 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/1000 with functional survival (CPC≤2) after early coronary angiography (95% CI, 144 fewer patients/1000 to 32 more patients/1000 with functional survival (CPC≤2) after early coronary angiography )].

For the critical outcome of functional survival at 90 days (CPC≤2) we identified low certainty evidence (downgraded for indirectness and imprecision) from one RCT (Lemkes 2019 39) enrolling 538 patients with ROSC after out-of-hospital cardiac arrest which showed no statistically significant difference with the use of early coronary angiography (I) when compared with late/no angiography (C) [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 with functional survival at 90 days (CPC≤2) (95% CI 97 fewer patients/1000 to 60 more patients/1000 with functional survival at 90 days (CPC≤2) after early coronary angiography)].

For the critical outcome of survival at hospital discharge/ 30 days we identified low certainty evidence (downgraded for very serious imprecision) from two RCTs (Lemkes 2019, Desch 2021 2544) enrolling 552 patients with ROSC after out-of-hospital cardiac arrest which showed no statistically significant difference with the use of early coronary angiography (I) when compared with late/no angiography (C) [OR 0.90 (95% CI, 0.63 to 1.28) RR 0.96 (95% CI, 0.84 to 1.10); absolute survival difference -0.03 (95% CI, -0.11 to 0.06) or 25 fewer patients/1000 survived to hospital discharge/30 days (95% CI, from 112 fewer patients/1000 to 55 more patients/1000 survived to hospital discharge/ 30 days after early coronary angiography)].

For the critical outcome of survival at 90 days, we identified low certainty evidence (downgraded for indirectness and imprecision) from one RCT (Lemkes 2019 39) enrolling 538 patients with ROSC after out-of-hospital cardiac arrest which showed no statistically significant difference with the use of 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 survival at 90 days after early coronary angiography (95% CI, 113 fewer patients/1000 to 50 more patients/ survival at 90 days after early coronary angiography)].

For the critical outcome of survival at 1 year, we identified low certainty evidence (downgraded for indirectness and imprecision) from one RCT (Lemkes 2020 1358) enrolling 538 patients with ROSC after out-of-hospital cardiac arrest which showed no statistically significant difference with the use of 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 at 1 year after early coronary angiography (95% CI, 113 fewer patients/1000 to 50 more patients/ survived at 1 year after early coronary angiography)]

The critical outcome of quality of life was assessed at 1 year with the RAND-36 physical and the RAND-36 mental scores.

For the assessment of quality of life with the RAND-36 physical score, we identified very low certainty evidence (downgraded for ROB, indirectness and imprecision) from one RCT (Lemkes 2020 1358) enrolling 235 patients with ROSC after out-of-hospital cardiac arrest, which showed no statistically significant difference with the use of early coronary angiography (I) when compared with late/no angiography (C). Corresponding median values and IQR ranges were median 49.2 (IQR 42.2 to 55.3) for the early coronary angiography group and 50.4 (IQR 44.9 to 55.2) for the delayed angiography group-difference not significant

For the assessment of quality of life with the RAND-36 mental score, we identified very low certainty evidence (downgraded for ROB, indirectness and imprecision) from one RCT (Lemkes 2020 1358) enrolling 235 patients with ROSC after out-of-hospital cardiac arrest, which showed no statistically significant difference with the use of early coronary angiography (I) when compared with late/no angiography (C). Corresponding median values and IQR ranges were median 51.3 (IQR 42.4 to 56.4) for the early coronary angiography group and median 50.0 (IQR 42.8 to 56.2) for the delayed angiography group-difference not significant

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

1. Intention to treat analysis (including all patients who were stratified in the intervention and control groups): We identified moderate certainty evidence (downgraded for serious indirectness) from one RCT (Lemkes 2019 39) enrolling 538 patients with ROSC after out-of-hospital cardiac arrest which showed that PCI was performed more frequently with early coronary angiography (I) when compared with late/no angiography [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 patients/1000 had PCI with early coronary angiography (95% CI, 11 more patients/1000 to 176 more patients/1000 had PCI with early coronary angiography)].
2. Per protocol analysis (including only patients who had angiography in the intervention and control groups): We identified moderate certainty evidence (downgraded for serious imprecision) from one RCT (Lemkes 2019 39) enrolling 437 patients with ROSC after out-of-hospital cardiac arrest which showed no statistically significant difference in PCI frequency with early coronary angiography (I) when compared with late/no angiography [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 with early coronary angiography (95% CI, 116 fewer patients/1000 to 63 more patients/1000 had PCI early coronary angiography)].

For the important outcome of coronary artery bypass graft (CABG) only an intention to treat analysis was performed.

We identified moderate certainty evidence (downgraded for serious imprecision) from one RCT (Lemkes 2019 39) enrolling 538 patients with ROSC after out-of-hospital cardiac arrest which showed no statistically significant difference in CABG with early coronary angiography (I) when compared with late/no angiography [OR 0.87 (95% CI, 0.45 to 1.67); RR 0.88 (95% CI, 0.48 to 1.60); absolute survival difference -0.01 (95% CI, -0.06 to 0.04) or 10 fewer patients/1000 with CABG after early coronary angiography (95% CI from 46 fewer to 50 more patients/1000 with CABG after early coronary angiography)].

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 observational study (Garcia 2016) (downgraded for serious indirectness and very serious imprecision) of 112 patients with an initial shockable rhythm which showed no association with the use of early coronary angiography (I) when compared with late/no angiography (C) [adjusted OR 1.89 (95% CI, 0.48 to 7.40]

For the critical outcome of functional survival at hospital discharge (CPC≤2) we identified very-low certainty evidence) from one observational study (Garcia 2016) (downgraded for serious indirectness and very serious imprecision) of 112 patients which showed no association with the use of early coronary angiography (I) when compared with late/no angiography (C) [adjusted OR 1.12 (95% CI, 0.30 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 ROB) from one observational study (Geri 2015 e002303) enrolling 1722 patients with ROSC after out-of-hospital cardiac arrest which showed an association with the use of early coronary angiography (I) when compared with late/no angiography (C) [adjusted OR 1.43 (95% CI, 1.12 to 1.83).

For the critical outcome of survival at 1-3 years, we identified very-low certainty evidence (downgraded for serious imprecision) from (Geri 2015 e002303) enrolling 1722 patients with ROSC after out-of-hospital cardiac arrest which showed no association with 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

Adverse Events by Cohort

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

For the important outcome of adverse events we identified three RCTs (Desch 2021 2544; Elfwen 2019; Kern 2020) that reported adverse events in this patient cohort. These included ischemic stroke, intracranial bleeds, recurrent cardiac arrest, cardiac arrhythmias, pneumonia, acute pulmonary edema, bleeding, and acute kidney failure. The certainty of evidence ranged from low to very low across all adverse events. There was no statistically significant difference noted in any of the adverse events with early coronary angiography compared to late/no coronary angiography. Analyses of adverse events that include the single new trial (Desch 2021) identified in this update are included here.

Ischemic Stroke or intracranial Hemorrhage

For the important outcome of ischemic stroke or intracranial hemorrhage, we identified low certainty evidence (downgraded for very serious imprecision) from two RCTs (Desch 2021 2544, Elfwen 2019 253) enrolling 578 patients with ROSC after out-of-hospital cardiac arrest which showed no statistically significant difference with early coronary angiography (I) when compared with late/no angiography (C) [OR 0.67 (95% CI, 0.20 to 2.28); RR 0.67 (95% CI, 0.20 to 2.24 ); absolute risk difference -0.01 (95% CI, -0.03 to 0.01) or 7 fewer patients/1000 had stroke or intracranial hemorrhage (95% CI, from 17 fewer patients/1000 to 26 more patients/1000 had stroke or intracranial hemorrhage after early coronary angiography)].

Bleeding

For the important outcome of moderate to severe bleeding we identified low certainty evidence (downgraded for very serious imprecision) from one RCT (Desch 2021 2544) enrolling 492 patients with ROSC after out-of-hospital cardiac arrest which showed no statistically significant difference with early coronary angiography (I) when compared with late/no angiography(C) [OR 1.35 (95% CI, 0.54 to 3.37); RR 1.34 (95% CI, 0.56 to 3.22); absolute risk difference 0.01 (95% CI, -0.02 to 0.05) or 12 more patients/1000 had moderate to severe bleeding (95% CI, from 16 fewer patients/1000 to 73 more patients/1000 had moderate to severe bleeding after early coronary angiography)].

Acute Kidney Failure

For the important outcome of acute kidney failure leading to renal-replacement therapy we identified low certainty evidence (downgraded for very serious imprecision) from one RCT (Desch 2021 2544) enrolling 500 patients with ROSC after out-of-hospital cardiac arrest which showed no statistically significant difference with early coronary angiography (I) when compared with late/no angiography (C) [OR 1.25 (95% CI, 0.78 to 1.99); RR 1.20 (95% CI, 0.82 to 1.76); absolute risk difference 0.03 (95% CI, -0.03 to 0.10) or 32 more patients/1000 had renal failure leading to renal-replacement therapy (95% CI, from 30 fewer patients/1000 to 114 more patients/1000 had renal failure leading to renal-replacement therapy after early coronary angiography)].

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 evidence)

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

Justification and Evidence to Decision Framework Highlights

This updated review used the search strategy from the 2021 CoSTR, restricting the inclusion criteria to only RCTs. We found one new RCT and one analysis of long-term outcomes from a previously included RCT. The new RCT allowed for additional meta-analyses for some critical outcomes, but the overall results, and therefore the treatment recommendations, remain unchanged.

Without ST-segment elevation

In making the above recommendations, the Task Force 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 early coronary angiography, compared with a combined control group of late coronary angiography and/or 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 most patients admitted to hospital after cardiac arrest do not die from cardiac complications but instead die as a result of neurologic injury. There are no significant differences in adverse event rates with either time interval.

With ST-segment elevation

No randomized trial has evaluated the early versus delayed timing of coronary angiography in comatose patients with ST segment elevation after cardiac arrest. 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 compelling evidence to change this approach in patients with ST segment elevation following cardiac arrest.

Knowledge Gaps

• Lack of consistent definition for comparable time intervals to treatment for early compared with late angiography and PCI.
• Whether early coronary angiography improves survival/survival with favorable neurologic outcome for post-arrest patients with ST elevation
• Whether angiography, compared with 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 in-hospital cardiac arrest.
• 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 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:

2022 ALS Et D Framework STEMI

2022 ALS CAG Evidence Profile tables update FINAL Feb 10

2022 ALS Early Coronary angiography Post ROSC 2022 Et D Framework No STEMI Update Feb 10

References

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