Author + information
- Received June 23, 2014
- Revision received September 10, 2014
- Accepted September 24, 2014
- Published online January 1, 2015.
- Mina Madan, MD∗∗ (, )
- Sigrun Halvorsen, MD†,
- Carlo Di Mario, MD‡,
- Mary Tan, MSc§,
- Cynthia M. Westerhout, PhD‖,
- Warren J. Cantor, MD¶,
- Michel R. Le May, MD#,
- Francesco Borgia, MD∗∗,
- Federico Piscione, MD††,
- Bruno Scheller, MD‡‡,
- Paul W. Armstrong, MD‖,
- Francisco Fernandez-Aviles, MD§§,
- Pedro L. Sanchez, MD§§,
- John J. Graham, MD‖‖,
- Andrew T. Yan, MD‖‖ and
- Shaun G. Goodman, MD§,‖‖
- ∗Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
- †Department of Cardiology, Oslo University Hospital HF Ullevål, Oslo, Norway
- ‡NIHR Cardiovascular BRU, Royal Brompton Hospital and NHLI Imperial College, London, United Kingdom
- §Canadian Heart Research Centre, Toronto, Ontario, Canada
- ‖Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada
- ¶Southlake Regional Medical Centre, Newmarket, Ontario, Canada
- #University of Ottawa Heart Institute, Ottawa, Ontario, Canada
- ∗∗Division of Cardiology, Federico II University, Naples, Italy
- ††Department of Medicine and Surgery, University of Salerno, Salerno, Italy
- ‡‡University Hospital, University of Saarland, Homburg/Saar, Germany
- §§Hospital General Universitario Gregorio Marañón–Complutense University, Madrid, Spain
- ‖‖Division of Cardiology, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada
- ↵∗Reprint requests and correspondence:
Dr. Mina Madan, Sunnybrook Health Sciences Centre, Room D380, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.
Objectives This study investigated the relationship between time to invasive assessment and outcomes among ST-segment elevation myocardial infarction patients randomized to early angiography after fibrinolysis.
Background The optimal timing of coronary angiography after fibrinolysis and the association with clinical outcomes is uncertain.
Methods Patient-level data from 6 randomized trials, with a median time to angiography <12 h after fibrinolysis, were pooled. The primary endpoint was 30-day death or reinfarction. The key secondary endpoint was in-hospital major bleeding. The relationship between fibrinolysis to angiography time and symptom onset to angiography time with outcomes was studied using 2- and 4-h intervals, respectively, and in multivariable models.
Results Among 1,238 patients, the median fibrinolysis to angiography time was 165 min, and the median symptom onset to angiography time was 5.33 h. The primary and key secondary endpoints occurred in 5.7% and 4.7%, respectively. These main endpoints did not vary significantly with increasing fibrinolysis to angiography time. Early angiography (<2 h) after fibrinolysis was not associated with increased bleeding. Recurrent ischemia increased with increasing fibrinolysis to angiography time (3.7% to 7.9%, p for trend = 0.02). Thirty-day and 1-year death/reinfarction and 30-day recurrent ischemia increased significantly with increasing symptom onset to angiography time. Neither fibrinolysis to angiography time nor symptom onset to angiography time was an independent predictor of the primary endpoint. Only symptom onset to angiography time was an independent predictor of 1-year death/reinfarction (hazard ratio: 1.07, 95% confidence interval: 1.02 to 1.12, p = 0.01).
Conclusions Very early angiography (<2 h) after fibrinolysis was not associated with an increased risk of 30-day death/reinfarction or in-hospital major bleeding, and angiography within 4 h after fibrinolysis was associated with reduced 30-day recurrent ischemia. A shorter symptom onset to angiography time (<4 h) was associated with reduced 30-day and 1-year death/reinfarction and 30-day recurrent ischemia. In the current environment of regional networks of 24/7 primary percutaneous coronary intervention (PCI) centers, the clinical implication of these findings is that patients initially treated with fibrinolysis should also be promptly transferred to the nearest PCI center for immediate angiography and PCI. (Early Percutaneous Coronary Intervention [PCI] After Fibrinolysis Versus Standard Therapy in ST Segment Elevation Myocardial Infarction [STEMI] Patients; NCT01014182)
The TRANSFER-AMI study was supported by a grant from the Canadian Institutes of Health Research and an unrestricted grant from Hoffman La Roche, Canada. Stents used in the TRANSFER-AMI study were provided by Abbott Vascular Canada. The CARESS-in-AMI trial was sponsored by the Italian Society of Interventional Cardiology by an unrestricted grant from Eli Lilly Critical Care Europe, Switzerland. The GRACIA-1 trial was supported in part by the Spanish Network for Cardiovascular Research RECAVA, the Instituto de Salud Carlos III, and the Spanish Ministry of Science and Innovation; stents used in the GRACIA-1 trial were provided by Abbott Vascular Spain. The WEST trial was supported by unrestricted research grants from Hoffman-La Roche, Sanofi Canada, and Eli Lilly Canada. The CAPITAL AMI study was supported by a peer-reviewed grant from the Canadian Institutes of Health Research and a CIHR Industry–Partnered Program with Hoffmann-La Roche Limited, Canada, and Guidant Corporation Canada. NORDISTEMI was funded by grants from the Scientific Board of the Eastern Norway Regional Health Authority, Hamar, Norway; the Ada and Hagbarth Waage’s Humanitære og Veldedige Stiftelse, Oslo, Norway; and the Innlandet Hospital Trust, Hamar, Norway. Dr. DiMario has received an institutional grant from Eli Lilly for the CARESS-in-AMI trial. Dr. Halvorsen has received speaker honoraria from AstraZeneca, Eli Lilly, Bristol-Myers Squibb, Pfizer, Sanofi, Bayer, Boehringer Ingelheim, and Merck Sharp & Dohme. Dr. Cantor is on the advisory board of Roche; and has received honoraria from Sanofi. Dr. Armstrong has received grants from Boehringer Ingelheim, Roche, Sanofi, Merck Sharp & Dohme, GlaxoSmithKline, Amylin Pharmaceuticals Inc., Regado Biosciences, and Merck & Co. Inc.; and has received honoraria from F. Hoffman. Dr. Graham has received speaker/consulting honoraria and/or research grant support from AstraZeneca, Eli Lilly, and Bristol-Myers Squibb. Dr. Yan has received honoraria from Sanofi. Dr. Goodman has received research grant support from Roche Canada and Sanofi; and support from the Heart and Stroke Foundation of Ontario for his role as Heart and Stroke Foundation (Polo) Chair at the University of Toronto. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received June 23, 2014.
- Revision received September 10, 2014.
- Accepted September 24, 2014.
- 2015 American College of Cardiology Foundation