Highlight
– An individual patient data meta‑analysis (IPDMA) combining COACT and TOMAHAWK (n=1,031) found no improvement in 1‑year survival with immediate coronary angiography compared with a delayed or selective strategy in comatose survivors of OHCA without ST‑segment elevation.
– Numerically fewer patients in the immediate group survived at 1 year (49.6% vs 53.4%), with a hazard ratio (stratified by trial) of 1.15 (95% CI, 0.96–1.37), not statistically significant.
– No prespecified subgroup (age, sex, rhythm, witnessed arrest, times to BLS/ROSC, prior CAD, diabetes, hypertension) showed significant treatment‑by‑subgroup interaction.
– These data support a selective, individualized approach rather than routine immediate angiography for all OHCA survivors without ST‑elevation.
Background: clinical context and unmet need
Out‑of‑hospital cardiac arrest (OHCA) is a major public health problem with high mortality and morbidity. When return of spontaneous circulation (ROSC) is achieved, clinicians face the immediate challenge of identifying and treating potentially reversible causes while optimizing neurologic recovery. Acute coronary occlusion is a common and treatable cause of OHCA, and for patients with ST‑segment elevation myocardial infarction (STEMI) guidelines uniformly recommend immediate coronary angiography and revascularization.
For the large subset of OHCA survivors who do not have ST‑segment elevation on the post‑ROSC ECG, the optimal timing of coronary angiography has been uncertain. Observational data suggested that culprit coronary lesions may be present even without ST elevation, prompting several randomized trials comparing immediate invasive coronary angiography versus a delayed or selective strategy. Initial trial results showed no short‑term survival advantage with routine immediate angiography, but questions remained about longer‑term outcomes and whether patient subgroups might benefit from tailored approaches.
Study design and methods
The IPDMA pooled individual participant data from two randomized controlled trials that compared immediate coronary angiography with a delayed or selective approach in patients successfully resuscitated from OHCA without ST‑segment elevation: COACT (Coronary Angiography After Cardiac Arrest) and TOMAHAWK (Immediate Unselected Coronary Angiography vs Delayed Triage in Survivors of Out‑of‑Hospital Cardiac Arrest Without ST‑Segment Elevation). Searches included MEDLINE, Embase, and Web of Science (to Sept 8, 2022) and trials met criteria of randomization and at least 1‑year follow‑up. Trial registration identifiers: PROSPERO CRD42022346559; COACT NTR4973; TOMAHAWK NCT02750462.
The primary endpoint for the pooled analysis was survival at 1 year. Secondary analyses evaluated heterogeneity of treatment effect across prespecified subgroups (age, sex, initial arrest rhythm, witnessed arrest, time to basic life support [BLS], time to ROSC, prior coronary artery disease, diabetes, hypertension) and assessed cardiovascular outcomes such as myocardial infarction and heart failure at 1 year. A one‑stage IPDMA approach was used, allowing adjustment and stratification by original trial.
Key findings
Population: The combined dataset comprised 1,031 patients enrolled across the two trials. Baseline characteristics reflected contemporary cohorts of comatose OHCA survivors without post‑ROSC ST‑elevation and excluded patients with obvious indications for immediate angiography (eg, STEMI or refractory cardiogenic shock in many cases). Care pathways and adjunctive therapies (targeted temperature management, intensive care) followed local protocols within trial frameworks.
Primary outcome — 1‑year survival
At 1 year, 259 of 522 patients (49.6%) randomized to immediate coronary angiography were alive versus 272 of 509 (53.4%) randomized to delayed or selective angiography. The stratified hazard ratio (HR) comparing immediate with delayed/selective angiography was 1.15 (95% CI, 0.96–1.37). An HR >1 in this analysis indicates a trend toward higher hazard (worse survival) with immediate angiography; however, the difference did not reach statistical significance. In practical terms, routine immediate angiography did not confer a survival advantage at 1 year and showed a numerical, non‑significant signal in the opposite direction.
Subgroup analyses
Across prespecified subgroups — including age categories, sex, initial arrest rhythm (shockable vs nonshockable), witnessed arrest, times to BLS and ROSC, and comorbidities (prior coronary artery disease, diabetes, hypertension) — there were no statistically significant treatment‑by‑subgroup interactions. P values for interaction across subgroups ranged broadly from 0.26 to 0.91, indicating no robust evidence that any examined subgroup derived a different effect from the timing strategy.
Cardiovascular events and safety
Rates of adjudicated myocardial infarction, recurrent ischemia, new heart failure, and other major cardiovascular events at 1 year were not meaningfully different between groups in the pooled data. Immediate angiography exposed some patients to invasive procedures without clear long‑term cardiovascular benefit when performed routinely in an unselected population without ST‑elevation. Procedural complications remained relatively infrequent but were not zero; decisions about immediate invasive strategies should weigh such procedural risks against expected benefits in individual patients.
Expert commentary and interpretation
This IPDMA provides the most comprehensive randomized evidence to date on 1‑year outcomes of immediate versus delayed/selective coronary angiography in OHCA survivors without ST‑elevation. The pooled analysis strengthens the external validity of prior trial results by increasing power and enabling subgroup analyses. The absence of a survival benefit at 1 year — and the lack of identifiable subgroups that clearly benefit from immediate angiography — supports a selective strategy over routine immediate catheterization for these patients.
Potential mechanisms explaining the lack of benefit include the heterogeneous etiology of OHCA (not all arrests are due to acute coronary occlusion), the possibility that immediate angiography may delay other time‑sensitive post‑resuscitation care (eg, neuroprotection, intensive care stabilization), and that many culprit lesions in this population may not be amenable to acute revascularization or may be identified and treated in a staged manner when clinically indicated.
Implications for practice
Clinicians should not reflexively take all comatose post‑OHCA patients without ST‑elevation to the cath lab for immediate angiography. Instead, a nuanced approach that incorporates clinical context is warranted:
– Reserve immediate angiography for patients with ECG evidence of STEMI, hemodynamic instability suggestive of ongoing ischemia, or other high‑probability features for an acute coronary culprit.
– For hemodynamically stable patients without ST‑elevation, consider early but not necessarily immediate coronary assessment guided by clinical findings, biomarkers, echocardiography, and serial ECGs; delayed angiography can be pursued if ischemic etiology becomes likely or if recovery permits.
– Continue comprehensive post‑resuscitation care (airway/ventilation, hemodynamic optimization, targeted temperature management as indicated, neuroprognostication) without undue procedural delay.
These findings align with a growing paradigm favoring selective invasive strategies informed by risk stratification rather than routine immediate angiography in all OHCA survivors without ST‑elevation.
Limitations and research gaps
Despite strengths, important limitations should be noted. The IPDMA includes only two randomized trials; although pooling increases precision, the total sample remains modest relative to the heterogeneity of OHCA populations. Both trials enrolled patients in high‑income, predominantly European centers; generalizability to other systems and resource settings may be limited. Trial protocols necessarily excluded some patients with extreme instability or very high pretest probability of coronary occlusion, so results should not be extrapolated to those scenarios. The IPDMA could not identify small subgroups that might benefit if such groups are rare or defined by features not captured in the pooled datasets (eg, specific biomarkers or imaging findings). Finally, while 1‑year survival is clinically meaningful, data on functional and cognitive outcomes beyond survival remain critical for shared decision‑making and were variably reported.
Conclusions and next steps
For comatose survivors of OHCA without post‑ROSC ST‑segment elevation, routine immediate coronary angiography does not improve 1‑year survival compared with a delayed or selective approach, and no clear subgroup was shown to derive a differential benefit. Current evidence supports an individualized strategy that prioritizes clinical assessment, hemodynamic status, and integrated post‑resuscitation care.
Future research priorities include the development and validation of early multimodal risk stratification tools (incorporating ECG, high‑sensitivity troponins, focused echocardiography, coronary CT angiography, and clinical features) to identify patients with a high likelihood of acute coronary occlusion who might benefit from immediate angiography. Trials that incorporate functional outcomes, cost‑effectiveness, and implementation across diverse healthcare systems would further inform practice.
Funding and registration
PROSPERO Identifier: CRD42022346559. COACT Netherlands Trial Register Identifier: NTR4973. TOMAHAWK ClinicalTrials.gov Identifier: NCT02750462.
Selected references
1. Spoormans EM, Thevathasan T, van Royen N, et al.; COACT and TOMAHAWK Trials Investigators. One‑Year Outcomes of Coronary Angiography After Out‑of‑Hospital Cardiac Arrest Without ST Elevation: An Individual Patient Data Meta‑Analysis. JAMA Cardiol. 2025;10(8):779–786. doi:10.1001/jamacardio.2025.1194
2. Lemkes JS, Janssens GN, van der Hoeven NW, et al.; COACT Investigators. Coronary Angiography after Cardiac Arrest without ST‑segment Elevation. N Engl J Med. 2019;380(15):1397–1407. doi:10.1056/NEJMoa1816906
3. Thiele H, Desch S, Freund A, et al.; TOMAHAWK Investigators. Immediate Unselected Coronary Angiography Versus Delayed Triage in Survivors of Out‑of‑Hospital Cardiac Arrest Without ST‑Segment Elevation (TOMAHAWK). N Engl J Med. 2021;385(18): 1–11. doi:10.1056/NEJMoa2032791
(Readers should consult the full trial publications and the pooled IPDMA report for detailed methods, complete event tables, and protocol‑level information.)
