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; Jacek Kubica, MD, PhD
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, email@example.com.
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.
Navarese EP, Gurbel PA, Andreotti F, Tantry U, Jeong Y, Kozinski M, 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. doi: 10.7326/0003-4819-158-4-201302190-00006
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Published: Ann Intern Med. 2013;158(4):261-270.
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.
To do the most comprehensive meta-analysis of current evidence on early versus delayed invasive treatment in NSTE-ACS.
MEDLINE, PubMed Central, and Google Scholar databases; conference proceedings; ClinicalTrials.gov registry; and Current Controlled Trials registry through May 2012.
Available randomized, controlled trials (RCTs) and observational studies comparing early versus delayed intervention in the NSTE-ACS population.
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.
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.
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.
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.
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Cardiology, Acute Coronary Syndromes, Coronary Heart Disease.
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