0

The full content of Annals is available to subscribers

Subscribe/Learn More  >
Reviews |

Optimal Timing of Coronary Invasive Strategy in Non–ST-Segment Elevation Acute Coronary Syndromes: A Systematic Review and Meta-analysis

Eliano P. Navarese, MD, PhD; Paul A. Gurbel, MD; Felicita Andreotti, MD, PhD; Udaya Tantry, PhD; Young-Hoon Jeong, MD, PhD; Marek Kozinski, MD, PhD; Thomas Engstrøm, MD; Giuseppe Di Pasquale, MD; Waclaw Kochman, MD; Diego Ardissino, MD; Elvin Kedhi, MD; Gregg W. Stone, MD; and Jacek Kubica, MD, PhD
[+] Article and Author Information

From Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland; Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, Maryland; Catholic University of the Sacred Heart, Rome, Italy; Rigshospitalet, Copenhagen, Denmark; Unità Ospedaliera di Cardiologia, Ospedale Maggiore, Bologna, Italy; Medical University of Gdansk, Swissmed Hospital, Gdansk, Poland; Azienda Ospedaliero-Universitaria di Parma, Parma, Italy; Maasstad Ziekenhuis, Rotterdam, the Netherlands; and Columbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, New York.

Note: The authors take full responsibility for data collection, data interpretation, and writing of the manuscript. Drs. Navarese and Andreotti had full access to all of the data and were finally responsible for submitting the manuscript for publication.

Acknowledgment: The present contribution is a project of Systematic Investigation and Research on Interventions and Outcomes (SIRIO)-MEDICINE, a group of senior scientists and fellows collaborating worldwide to pursue research and innovation in medicine.

Potential Conflicts of Interest: Dr. Gurbel: Consultancy: Daiichi Sankyo, Eli Lilly, Pozen, Novartis, Bayer, AstraZeneca, Accumetrics, Nanosphere, Sanofi-Aventis, Boehringer Ingelheim, Merck, Medtronic, Iverson Genetics, CSL, Haemonetics. Dr. Andreotti: Board membership: Bayer; Consultancy: Bayer, Bristol-Myers Squibb–Pfizer, Eli Lilly, Daiichi Sankyo; Payment for lectures: AstraZeneca, Bayer, Eli Lilly, Pfizer, Daiichi Sankyo. Dr. Jeong: Grant: Boehringer-Ingelheim, Otsuka, Accumetrics, Haemonetics; Consulting fee or honorarium: Sanofi-Aventis, Daiichi Sankyo/Eli Lilly, Nanospher, Haemonetics, Otsuka; Support for travel to meetings for the study or other purposes: Haemonetics. Dr. Ardissino: Grant (money to institution): Eli Lilly, AstraZeneca, Sanofi-Aventis, Boston Scientific, Medtronic, Bayer; Consulting fee or honorarium: Eli Lilly, AstraZeneca, Sanofi-Aventis, Boston Scientific; Payment for lectures, including service on speakers bureaus: Eli Lilly, AstraZeneca, Sanofi-Aventis, Boston Scientific, Medtronic, Bayer. Dr. Stone: Consultancy: Osprey Pharmaceuticals, Reva, Merck, Boston Scientific, Abbott Vascular, AstraZeneca, Eli Lilly–Daiichi Sankyo partnership, Bristol-Myers Squibb–Sanofi-Aventis partnership, Otsuka, The Medicines Company, Ortho–McNeil, Gilead Sciences, InspireMD, TherOx, Atrium, Volcano, InfraReDx, Medtronic, Genentech, GlaxoSmithKline, Miracor, MPP Group, Lutonix, Velomedix, CSI, St. Jude, Thoratec; Honoraria: Edwards LifeSciences, Vascular Solutions; Stock/stock options: CoreValve, Biostar I and II funds, MedFocus I, II, and Accelerator funds, Caliber, FlowCardia, Ovalum, Guided Delivery Systems, Arstasis, MiCardia, AccessClosure, Embrella Cardiovascular, VNT. All other authors have no disclosures. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-0590.

Requests for Single Reprints: Eliano P. Navarese, MD, PhD, Department of Cardiology and Internal Medicine, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Sklodowskiej-Curie Street No. 9, 85-094 Bydgoszcz, Poland; e-mail, eliano.navarese@alice.it.

Current Author Addresses: Drs. Navarese, Kozinski, and Kubica: Department of Cardiology and Internal Medicine, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Skłodowskiej-Curie Street No. 9, 85-094 Bydgoszcz, Poland.

Drs. Gurbel, Tantry, and Jeong: Center for Thrombosis Research, Cardiac Catheterization Laboratory, 2401 West Belvedere Avenue, Baltimore, MD 21215.

Dr. Andreotti: Department of Cardiovascular Sciences, Catholic University, Largo A. Gemelli 8, 00168 Rome, Italy.

Dr. Engstrøm: Cardiac Catheterization Laboratory, Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen 2100, Denmark.

Dr. Di Pasquale: Unità Operativa di Cardiologia, Ospedale Maggiore, Largo Bartolo Nigrisoli 2, 40133 Bologna, Italy.

Dr. Kochman: Faculty of Health Sciences, Medical University of Gdansk, Swissmed Hospital, 44 Wilenska Street, 80-215 Gdansk, Poland.

Dr. Ardissino: Unità Operativa di Cardiologia, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43100 Parma, Italy.

Dr. Kedhi: Department of Cardiology, Maasstadziekenhuis, Maasstadweg, 3079DZ Rotterdam, the Netherlands.

Dr. Stone: Columbia University Medical Center, New York-Presbyterian Hospital, The Cardiovascular Research Foundation, New York, NY 10022.

Author Contributions: Conception and design: E.P. Navarese, P.A. Gurbel, M. Kozinski, T. Engstrøm, G. Di Pasquale, J. Kubica.

Analysis and interpretation of the data: E.P. Navarese, F. Andreotti, Y.H. Jeong, M. Kozinski, T. Engstrøm, G. Di Pasquale, E. Kedhi, G.W. Stone, J. Kubica.

Drafting of the article: E.P. Navarese, P.A. Gurbel, U. Tantry, T. Engstrøm, J. Kubica.

Critical revision of the article for important intellectual content: E.P. Navarese, P.A. Gurbel, F. Andreotti, U. Tantry, M. Kozinski, T. Engstrøm, W. Kochman, D. Ardissino, E. Kedhi, G.W. Stone, J. Kubica.

Final approval of the article: E.P. Navarese, P.A. Gurbel, F. Andreotti, U. Tantry, M. Kozinski, T. Engstrøm, G. Di Pasquale, W. Kochman, D. Ardissino, E. Kedhi, G.W. Stone, J. Kubica.

Provision of study materials or patients: E.P. Navarese.

Statistical expertise: E.P. Navarese.

Administrative, technical, or logistic support: J. Kubica.

Collection and assembly of data: E.P. Navarese, F. Andreotti, Y.H. Jeong, M. Kozinski.


Ann Intern Med. 2013;158(4):261-270. doi:10.7326/0003-4819-158-4-201302190-00006
Text Size: A A A

Background: The optimal timing of coronary intervention in patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACSs) is a matter of debate. Conflicting results among published studies partly relate to different risk profiles of the studied populations.

Purpose: To do the most comprehensive meta-analysis of current evidence on early versus delayed invasive treatment in NSTE-ACS.

Data Sources: MEDLINE, PubMed Central, and Google Scholar databases; conference proceedings; ClinicalTrials.gov registry; and Current Controlled Trials registry through May 2012.

Study Selection: Available randomized, controlled trials (RCTs) and observational studies comparing early versus delayed intervention in the NSTE-ACS population.

Data Extraction: Data were extracted for populations, interventions, outcomes, and risk of bias. All-cause mortality was the prespecified primary end point. The longest follow-up available in each study was chosen. The odds ratio with 95% CI was the effect measure.

Data Synthesis: Seven RCTs (5370 patients) and 4 observational studies (77 499 patients) were included. Early intervention was less than 20 hours after hospitalization or randomization for RCTs and 24 hours or less for observational studies. Meta-analysis of the RCTs was inconclusive for a survival benefit associated with the early invasive strategy (odds ratio, 0.83 [95% CI, 0.64 to 1.09]; P = 0.180); a similar result emerged from the observational studies. With early versus late intervention, the odds ratios in the RCTs were 1.15 (CI, 0.65 to 2.01; P = 0.63) and 0.76 (CI, 0.56 to 1.04; P = 0.090) for myocardial infarction and major bleeding during follow-up, respectively.

Limitation: Current evidence from RCTs is limited by the small overall sample size, low numbers of events in some trials, and heterogeneity in the timing of intervention and in patient risk profiles.

Conclusion: At present, there is insufficient evidence either in favor of or against an early invasive approach in the NSTE-ACS population. A more definitive RCT is warranted to guide clinical practice.

Primary Funding Source: None.

Figures

Grahic Jump Location
Appendix Figure 1.

Summary of evidence search and selection.

RCT = randomized, controlled trial.

Grahic Jump Location
Grahic Jump Location
Figure 1.

Individual and summary ORs for mortality in randomized trials and observational studies comparing early versus delayed intervention.

ABOARD = Angioplasty to Blunt the Rise of Troponin in Acute Coronary Syndromes Randomized for an Immediate or Delayed Intervention; ACUITY = Acute Catheterization and Urgent Intervention Triage Strategy; CRUSADE = Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines; D-L = DerSimonian and Laird; ELISA = Early or Late Intervention in Unstable Angina; GRACE = Global Registry of Acute Coronary Events; ISAR-COOL = Intracoronary Stenting With Antithrombotic Regimen Cooling Off; LIPSIA-NSTEMI = Leipzig Immediate Versus Early and Late Percutaneous Coronary Intervention Trial in Non–ST-Segment Elevation Myocardial Infarction; OR = odds ratio; SYNERGY = Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors; TIMACS = Timing of Intervention in Acute Coronary Syndromes.

Grahic Jump Location
Grahic Jump Location
Figure 2.

Individual and summary ORs for myocardial infarction in randomized trials and observational studies comparing early versus delayed intervention.

ABOARD = Angioplasty to Blunt the Rise of Troponin in Acute Coronary Syndromes Randomized for an Immediate or Delayed Intervention; ACUITY = Acute Catheterization and Urgent Intervention Triage Strategy; CRUSADE = Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines; D-L = DerSimonian and Laird; ELISA = Early or Late Intervention in Unstable Angina; ISAR-COOL = Intracoronary Stenting With Antithrombotic Regimen Cooling Off; LIPSIA-NSTEMI = Leipzig Immediate Versus Early and Late Percutaneous Coronary Intervention Trial in Non–ST-Segment Elevation Myocardial Infarction; OR = odds ratio; SYNERGY = Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors; TIMACS = Timing of Intervention in Acute Coronary Syndromes.

Grahic Jump Location
Grahic Jump Location
Figure 3.

Individual and summary ORs for major bleeding complications in randomized trials and observational studies comparing early versus delayed intervention.

ABOARD = Angioplasty to Blunt the Rise of Troponin in Acute Coronary Syndromes Randomized for an Immediate or Delayed Intervention; ACUITY = Acute Catheterization and Urgent Intervention Triage Strategy; D-L = DerSimonian and Laird; ELISA = Early or Late Intervention in Unstable Angina; GRACE = Global Registry of Acute Coronary Events; ISAR-COOL = Intracoronary Stenting With Antithrombotic Regimen Cooling Off; LIPSIA-NSTEMI = Leipzig Immediate Versus Early and Late Percutaneous Coronary Intervention Trial in Non–ST-Segment Elevation Myocardial Infarction; OR = odds ratio; SYNERGY= Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors; TIMACS = Timing of Intervention in Acute Coronary Syndromes.

Grahic Jump Location
Grahic Jump Location
Appendix Figure 2.

Individual and summary ORs for refractory ischemia and repeated revascularization in patients treated with early versus delayed intervention.

ABOARD = Angioplasty to Blunt the Rise of Troponin in Acute Coronary Syndromes Randomized for an Immediate or Delayed Intervention; D-L = DerSimonian and Laird; ELISA = Early or Late Intervention in Unstable Angina; ISAR-COOL = Intracoronary Stenting With Antithrombotic Regimen Cooling Off; LIPSIA-NSTEMI = Leipzig Immediate Versus Early and Late Percutaneous Coronary Intervention Trial in Non–ST-Segment Elevation Myocardial Infarction; OR = odds ratio; TIMACS = Timing of Intervention in Acute Coronary Syndromes.

Grahic Jump Location

Tables

References

Letters

CME Activities are only available to ACP members and Individual Annals subscribers. If you are a member or a subscriber please sign in. Otherwise please become a member or subscribe to Annals.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment
Early vs. Late Percutaneous Coronary Intervention for Non-ST-Segment Elevation Acute Coronary Syndromes
Posted on February 25, 2013
Gen-Min Lin
Hualien-Armed Forces general Hospital, Hualien, Taiwan
Conflict of Interest: None Declared

To the Editor:

Early versus late percutaneous coronary intervention (PCI) strategy for non-ST segment elevation acute coronary syndromes (NSTE-ACS) showed similar results with regard to the subsequent survival benefit, myocardial infarction and major bleeding in this study.1  However, the conflicting results among the enrolled randomized trials and observational registries should be carefully interpreted and reviewed before they were put together in a meta-analysis. As is known, patients with history of established coronary artery disease, chronic heart failure and other peripheral vascular disease have been adapted to an ischemia-conditioning circumstance. These patients were characterized with more severe coronary anatomy and could be tolerant to longer myocardial ischemia time than those with first time NSTE-ACS. In addition, patients with previous cardiovascular diseases usually died of sudden death rather than developed myocardial infarction in follow-up. Therefore, in our opinion, further subgroup meta-analysis according to a history of cardiovascular diseases should be carried out separately to determine the optimal timing of PCI for patients with NSTE-ACS.

Conflict of interest None

Reference

1. Navarese EP; Gurbel PA; Andreotti F, et al. Optimal Timing of Coronary Invasive Strategy in Non–ST-Segment Elevation Acute Coronary Syndromes: A Systematic Review and Meta-analysis. Ann Intern Med. 2013;158:261-270

Author's Response
Posted on March 28, 2013
Eliano P. Navarese
Nicolaus Copernicus University
Conflict of Interest: None Declared

As already stated in the present article [1] and repeated by Lin, the conflicting results among published randomized controlled trials (RCTs) partly relate to different risk profiles of the studied populations; previous RCTs enrolled low-risk populations; a comprehensive meta-analysis taking into account also RCTs with high patient's risk profile provides the most complete source of evidence and crucial findings, as also shown also in previous analyses [2]. Noteworthy, The strength of our results is confirmed by different sensitivity analyses performed. Lin is incorrect in stating the conflicting results between RCTs and observational data; indeed, we report strongly concordant findings (e.g. odds ratio for mortality in RCT and observational studies: 0.83 and 0.80). Lin is once more incorrect in depicting an important different ischemia time from population of RCT; the included observational studies were sub- analyses of RCTs sharing the same population from the original trial or multicenter registries in which the assessment of clinical outcomes was checked by an independent events committee or by using standardized case report forms; moreover, the stratified analysis conducted on non randomized data poses the perspective of the real word that clinician face in their clinical practice; conversely, sub group analyses based on the previous history of cardiovascular diseases could have the only effect to increase the play of chance. In conclusion, this meta-analysis is the most complete and valuable resource on timing of invasive approach in acute coronary syndrome available to date and in this sense informs clinical practice; a similar powered RCT enrolling high risk profile population is largely awaited while difficult to conduct because of economical and logistic issues.

 References

1. Navarese EP; Gurbel PA; Andreotti F, et al. Optimal Timing of Coronary Invasive Strategy in Non–ST-Segment Elevation Acute Coronary Syndromes: A Systematic Review and Meta-analysis. Ann Intern Med. 2013;158:261-270.

2. De Luca G, Navarese E, Marino P. Risk profile and benefits from Gp IIb-IIIa inhibitors among patients with ST-segment elevation myocardial infarction treated with primary angioplasty: a meta-regression analysis of randomized trials. Eur Heart J. 2009;30:2705-13.

Submit a Comment

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Related Point of Care
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)