Timing of Coronary Invasive Strategy in Non–ST-Segment Elevation Acute Coronary Syndromes and Clinical Outcomes
Open accessAbstract
Objectives The aim of this study was to compare an early versus a delayed invasive strategy in non-ST-segment elevation acute coronary syndromes by performing a meta-analysis of all available randomized controlled clinical trials.Background An invasive approach is recommended to prevent death and myocardial infarction in non-ST-segment elevation acute coronary syndromes. However, the timing of angiography and the subsequent intervention, when required, remains controversial.Methods A previous meta-analysis of 7 randomized clinical trials comparing early and delayed invasive strategies in non-ST-segment elevation acute coronary syndromes with 3 new randomized clinical trials identified in a search of the published research (n = 10 trials, n = 6,397 patients) was updated.Results The median time between randomization and angiography ranged from 0.5 to 14.0 h in the early group and from 18.3 to 86.0 h in the delayed group. There was no difference in the primary endpoint of mortality (4% vs. 4.7%; random-effects odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.67 to 1.09; p = 0.20; I 2 = 0%). The rate of myocardial infarction was also similar (6.7% vs. 7.7%; random-effects OR: 0.88; 95% CI: 0.53 to 1.45; p = 0.62; I 2 = 77.5%). An early strategy was associated with a reduction in recurrent ischemia or refractory angina (3.8% vs. 5.8%; random-effects OR: 0.54; 95% CI: 0.40 to 0.74; p < 0.01; I 2 = 28%) and a shorter in-hospital stay (median 112 h [interquartile range: 61 to 158 h] vs. 168 h [interquartile range: 90.3 to 192 h]; random-effects standardized mean difference -0.40; 95% CI: -0.59 to -0.21; p < 0.01; I 2 = 79%). Major bleeding was similar in the 2 groups (3.9% vs. 4.2%; random-effects OR: 0.94; 95% CI: 0.73 to 1.22; p = 0.64; I 2 = 0%).Conclusions An early invasive strategy does not reduce the risk for death or myocardial infarction compared with a delayed strategy. Recurrent ischemia and length of stay were significantly reduced with an early invasive strategy.
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Since diabetes is one of the risk factors of poor prognosis, patients with diabetes may benefit significantly more from the early invasive approach than those without diabetes.
“Since diabetes is one of the risk factors of poor prognosis, patients with diabetes may benefit significantly more from the early invasive approach than those without diabetes.417,443”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [443]
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“This is confirmed by all published meta-analyses on this topic 1–5 showing that early intervention—despite the large number of patients included—only results in a statistically significant reduction of the incidence of recurrent ischaemia and duration of hospital stay, but not in mortality or…”
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“Recent meta-analyses demonstrated that an early invasive strategy does not reduce mortality compared with a delayed invasive strategy in patients with NSTEMI.5,6 In the era of newer-generation drug-eluting stents (DESs), there are many reports concerning this topic in patients with ST-segment elevation myocardial infa…”
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A Saudi Heart Association Position Statement on Cardiovascular Diseases and Diabetes Mellitus
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Murrone, A., di Uccio, F. S., Amodeo, V., Aspromonte, N., Caldarola, P., Casella, G., Cipriani, M., Luca, L. D., Lenarda, A. D., Domenicucci, S., et al. (2021) · European Heart Journal Supplements · doi:10.1093/eurheartj/suab068 · Cited by 5 · see citing works
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“endpoints (CV mortality or MI), but only on recurrent ischemic events.(6) Therefore, the composite endpoint that we have chosen looks appropriate to test our hypothesis and is of clinical interest because it reflects how patients are managed in current practice.”
BackgroundResultInfluentialSelf-citationPre-Treatment With Oral P2Y12 Inhibitors in Non–ST-Segment Elevation Acute Coronary Syndromes
Ferreiro, J. L. (2020) · JACC: Cardiovascular Interventions · doi:10.1016/j.jcin.2020.02.036 · Cited by 5 · see citing works
Patel, B. D., Carson, P., Shah, M. K., Garg, L., Agarwal, M. A., Agrawal, S., Arora, S., Steigerwalt, S. P., Bavry, A. A., Dusaj, R., et al. (2017) · Clinical Cardiology · doi:10.1002/clc.22828 · Cited by 4 · see citing works
“Very recently, a published meta-analysis concluded that an early invasive strategy does not reduce the risk for death of MI compared with a delayed strategy.(11) However, none of the published studies examined the effect of an early vs delayed strategy on outcomes in patients with CKD.”
ResultLeng, W., Yang, J., Li, W., Wang, Y., & Yang, Y. (2017) · American Heart Journal · doi:10.1016/j.ahj.2017.10.022 · Cited by 4 · see citing works
Fagel, N. D., Amoroso, G., Rabbering, T., Gescher, F. M., Vink, M. A., Slagboom, T., van der Schaaf, R. J., Herrman, J. R., Patterson, M. S., Vos, N. S., et al. (2021) · Catheterization and Cardiovascular Interventions · doi:10.1002/ccd.29873 · Cited by 3 · see citing works
Kim, Y. H., Her, A., Rha, S., Choi, C. U., Choi, B. G., Kim, J. B., Park, S., Kang, D. O., Park, J. Y., Park, S., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-15593-w · Cited by 3 · see citing works
Velagapudi, P., Turagam, M. K., Kolte, D. S., Khera, S., Parikh, P. J., Hyder, O. N., Aronow, H. D., & Abbott, J. D. (2017) · Expert Review of Cardiovascular Therapy · doi:10.1080/14779072.2018.1391092 · Cited by 2 · see citing works
Küçük, U. (2023) · Turk Kardiyoloji Dernegi Arsivi-Archives of the Turkish Society of Cardiology · doi:10.5543/tkda.2022.65627 · Cited by 2 · see citing works
Fabin, N., Cenko, E., Bergami, M., Yoon, J., Vadalà, G., Mendieta, G., Kedev, S. A., Kostov, J., Vavlukis, M., Vraynko, E., et al. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvae190 · Cited by 2 · see citing works
“Previous meta-analyses 27,35,36 also found no significant difference in hard clinical endpoints between early and delayed invasive strategies in NSTE-ACS.”
ZHENG, J.-J., Si, Y., Xia, T., Lu, B.-J., Zeng, C.-Y., & Wang, W. (2024) · 老年心脏病学杂志：英文版 · doi:10.26599/1671-5411.2024.08.003 · Cited by 2 · see citing works
Killi, N., Mariottini, G. L., Tekin, İ., & Azaiez, K. (2025) · Journal of Biological Research - Bollettino della Società Italiana di Biologia Sperimentale · doi:10.4081/jbr.2025.12699 · Cited by 2 · see citing works
The Strategy of Management Patients with non-ST Elevation Acute Coronary Syndrome
Prilutskaya, Y. A., & DVORETSKI, L. I. (2019) · Kardiologiia · doi:10.18087/cardio.2019.9.n366 · Cited by 2 · see citing works
Shneĭder, I. A., Цой, В. Г., & Фоменко, М. С. (2020) · Angiology and vascular surgery · doi:10.33529/angio2020425 · Cited by 2 · see citing works
“Recent retrospective works showed no difference between the early and delayed invasive policy [3, 14, 15].”
BackgroundIschemia-Guided Approach Versus Early Invasive Approach for NSTE-ACS: How Early Is Early?
Denktas, A. E. (2021) · Current Cardiology Reports · doi:10.1007/s11886-021-01462-x · Cited by 2 · see citing works
Han, Y., Sun, S., Qiao, B., Liu, H., Zhang, C., Wang, B., Wei, S., & Chen, Y. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.1000554 · Cited by 2 · see citing works
The Rationale and Design of the KOSovan Acute Coronary Syndrome (KOS-ACS) Registry
Bajraktari, G., Elezi, S., Bytyçi, I., Ibrahimi, P., Abdyli, G., Pllana, E., Karahoda, R., Batalli, A., Poniku, A., Shatri, M., et al. (2024) · Diagnostics · doi:10.3390/diagnostics14141486 · Cited by 2 · see citing works
Ota, Y., Sakakura, K., Jinnouchi, H., Taniguchi, Y., Yamamoto, K., Tsukui, T., Hatori, M., Kasahara, T., Watanabe, Y., Ishibashi, S., et al. (2025) · Internal Medicine · doi:10.2169/internalmedicine.4805-24 · Cited by 1 · see citing works
Coronary angiography in non-ST-elevation acute myocardial infarction – whom and when?
Bønaa, K. H., & Steigen, T. K. (2017) · Tidsskrift for Den norske legeforening · doi:10.4045/tidsskr.17.0492 · Cited by 1 · see citing works
Navarese, E. P., Wernly, B., Lichtenauer, M., Pepe, M., Wańha, W., Ferrante, G., Frediani, L., Veulemans, V., Zeus, T., Westenfeld, R., et al. (2018) · Journal of Thoracic Disease · doi:10.21037/jtd.2017.11.125 · Cited by 1 · see citing works
“Currently there are ten randomized controlled trials (RCTs) that have compared early versus delayed intervention in NSTE-ACS patients with a large variation in timing, ranging from immediate up to 24 hours in the early group (7-17).”
BackgroundГоловина, Т. С., Neverova, Y. N., & Tarasov, R. S. (2021) · Russian Journal of Cardiology · doi:10.15829/1560-4071-2021-4259 · Cited by 1 · see citing works
Revascularization Strategies in Multivessel Coronary Artery Disease
Caputi, C. G., Ricci, F., Innocentiis, C. D., Caterina, R. D., & Zimarino, M. (2018) · Springer eBooks · doi:10.1007/978-3-319-55994-0_53 · Cited by 1 · see citing works
Li, Y., Wang, C., Yue, N., Zhao, H., Cao, Z., Du, X., & Kuan, W. (2020) · Journal of International Medical Research · doi:10.1177/0300060520966500 · Cited by 1 · see citing works
Park, Y. J., Lee, J. H., Kim, H. J., Park, B. E., Kim, H. N., Jang, S. Y., Bae, M. H., Yang, D. H., Park, H. S., Cho, Y., et al. (2020) · International Journal of Cardiology · doi:10.1016/j.ijcard.2020.11.059 · Cited by 1 · see citing works
Kim, Y. H., Her, A., Rha, S., Choi, C. U., Choi, B. G., Kim, J. B., Park, S., Kang, D. O., Park, J. Y., Park, S., et al. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11164780 · Cited by 1 · see citing works
Invasive Strategy After Non–ST-Segment Elevation Acute Coronary Syndrome
Jneid, H. M. (2016) · JACC: Cardiovascular Interventions · doi:10.1016/j.jcin.2016.10.011 · Cited by 1 · see citing works
“(1) added 3 RCTs and 1,027 subjects to the metaanalysis by Navarese et al.”
BackgroundMethodResultInfluentialLemesle, G., Schurtz, G., Verdier, B., & Bonello, L. (2023) · Heart · doi:10.1136/heartjnl-2023-323688 · Cited by 1 · see citing works
Self-citationTiming of invasive coronary angiography in non-ST-elevation acute coronary syndrome: can we wait?
Bonello, L., & Lemesle, G. (2024) · EuroIntervention · doi:10.4244/eij-d-23-01090 · Cited by 1 · see citing works
Self-citationCaterina, R. D., & Marzilli, M. (2018) · International Journal of Cardiology · doi:10.1016/j.ijcard.2018.01.016
O’Donoghue, M. L., & Bergmark, B. A. (2018) · JACC: Cardiovascular Interventions · doi:10.1016/j.jcin.2018.01.001
Bonello, L., Laine, M., & Lemesle, G. (2019) · Circulation · doi:10.1161/circulationaha.118.037810
Self-citationGómez-Polo, J. C., Ferrera, C., Ruiz-Pizarro, V., García-Amado, C. R., Gómez-Álvarez, Z., Romero-Delgado, T., Noriega, F. J., Macaya, C., Fernández‐Ortíz, A., & Viana‐Tejedor, A. (2019) · REC interventional cardiology (English Edition) · doi:10.24875/recice.m19000076
Lim, C., Hong, S., Kim, B., Lee, Y., Lee, S., Suh, Y., Ahn, C., Kim, J., Hong, M., & Jang, Y. (2022) · Journal of Cardiovascular Intervention · doi:10.54912/jci.2022.0003
MYOCARDIAL INFARCTION IN A PATIENT WITH COMPLICATED ANATOMY OF CORONARY VESSELS AND ANEMIC SYNDROME
Kozik, V. A., Lozhkina, N. G., Glebchenko, E. A., Khasanova, M. H., & Куимов, А. Д. (2017) · Siberian medical review · doi:10.20333/2500136-2017-2-109-111
Işık, G. Ç., ŞAFAK, S., GÜNSAY, R. H., & Çevik, Y. (2022) · MIDDLE BLACK SEA JOURNAL OF HEALTH SCIENCE · doi:10.19127/mbsjohs.1081086
Tarranza, J. L., Bongon, C. J., Valdez, M. M., Tiopianco, J. P., Reyes, A., Ona, J. P., Reyes, D. R., Ramirez, M. F. L., Lara, A. C. F. D., Mendoza, C., et al. (2022) · Journal of Medicine University of Santo Tomas · doi:10.35460/2546-1621.2022-sp03
“Once STEMI has been excluded, patients may be triaged according to their ECG findings and cardiac biomarkers result.”
InfluentialCarvalho, C. R., Bernardo, M. C. R., Moreira, I. M., Mateus, P., Baptista, A., Moreira, I., & on behalf of the Portuguese Registry of Acute Coronary Syndromes (2024) · Coronary Artery Disease · doi:10.1097/mca.0000000000001457
Lim, Y., Park, S.-H., Joo, D., Lee, Y.-K., Oh, S. K., Lee, S. H., Ahn, J. H., Hyun, D. Y., Cho, K. H., Sim, D. S., et al. (2025) · Cardiovascular revascularization medicine · doi:10.1016/j.carrev.2025.09.016
Comparison of Troponin in a Prehospital Blood Sample and Risk Scores
Benito, J. F. D., Ramos-Rodríguez, A., Portillo, E. C., Vegas, C. D. P., López‐Izquierdo, R., Fernández, F. T. M., de la Torre, S. O., Villamor, M. Á. C., García, A. S., & Rodríguez, F. M. (2026) · Diagnostics · doi:10.3390/diagnostics16172688
“European and North American guidelines recommend coronary angiography within 24 h in high-risk patients [1,2], and every minute of delay to reperfusion is associated with higher mortality [3,4].”
- Authors
- Bonello, L., Laine, M., Puymirat, E., Lemesle, G., Thuny, F., Paganelli, F., Michelet, P., Roch, A., Kerbaul, F., & Boyer, L.
- Affiliations
- Inserm (FR)
- Aix-Marseille Université (FR)
- Hôpital de la Timone (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Hôpital Nord (FR)
- Assistance Publique Hôpitaux de Marseille (FR)
- Corresponding author
- Bonello, Laurent
- ORCID
- Venue
- JACC: Cardiovascular Interventions
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 9
- Issue
- 22
- Pages
- 2267-2276
- ISSN
- 1876-7605 (ISSN-L)
- 1936-8798
- OpenAlex
- W2552754651
- Cited by
- 81
- References
- 29
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 7 · 2023: 6 · 2022: 9 · 2021: 12 · 2020: 9 · 2019: 15 · 2018: 9 · 2017: 9 · 2016: 1
- FWCI
- 9.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- JACC: Cardiovascular Interventions (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Health Sciences › Medicine › Surgery › Coronary Interventions and Diagnostics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Keywords
- non-ST-elevation acute coronary syndrome, early invasive strategy, coronary angiography, myocardial infarction, mortality, recurrent ischemia, refractory angina, length of hospital stay, major bleeding, clinical outcomes, randomized controlled trials meta-analysis, bleeding risk stratification
- MeSH terms
- Non-ST Elevated Myocardial Infarction, Coronary Artery Bypass, Hemorrhage, Humans, Length of Stay, Recurrence, Risk Factors, Time Factors, Odds Ratio, Randomized Controlled Trials as Topic, Treatment Outcome, Coronary Angiography, Risk Assessment, Acute Coronary Syndrome, Time-to-Treatment, Percutaneous Coronary Intervention
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