Author + information
- Received October 14, 2013
- Revision received October 22, 2013
- Accepted October 22, 2013
- Published online February 25, 2014.
- Philippe Généreux, MD∗,†,‡,
- Gregg W. Stone, MD∗,†,
- Robert A. Harrington, MD§,
- C. Michael Gibson, MD‖,
- Ph. Gabriel Steg, MD¶,
- Sorin J. Brener, MD†,#,
- Dominick J. Angiolillo, MD, PhD∗∗,
- Matthew J. Price, MD††,
- Jayne Prats, PhD‡‡,
- Laura LaSalle, MPH†,
- Tiepu Liu, MD, PhD††,
- Meredith Todd, BSc††,
- Simona Skerjanec, PharmD††,
- Christian W. Hamm, MD§§,
- Kenneth W. Mahaffey, MD§,
- Harvey D. White, DSc‖‖,
- Deepak L. Bhatt, MD, MPH¶¶∗ (, )
- for the CHAMPION PHOENIX Investigators
- ∗Columbia University Medical Center, New York, New York
- †Cardiovascular Research Foundation, New York, New York
- ‡Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada
- §Stanford University, Stanford, California
- ‖Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
- ¶Institut National de la Santé et de la Recherche Médicale–Unité 698, Assistance Publique–Hôpitaux de Paris, Hôpital Bichat, and Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France, and Royal Brompton Hospital, London, United Kingdom
- #New York Methodist Hospital, Brooklyn, New York
- ∗∗University of Florida College of Medicine-Jacksonville, Jacksonville, Florida
- ††Scripps Clinic and Scripps Translational Science Institute, La Jolla, California
- ‡‡The Medicines Company, Parsippany, New Jersey
- §§University of Giessen and Kerckhoff Heart Center, Bad Nauheim, Germany
- ‖‖Auckland City Hospital, Auckland, New Zealand
- ¶¶Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts
- ↵∗Reprint requests and correspondence:
Dr. Deepak L. Bhatt, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115.
Objectives This study sought to evaluate the clinical impact of intraprocedural stent thrombosis (IPST), a relatively new endpoint.
Background In the prospective, double-blind, active-controlled CHAMPION PHOENIX (Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention) trial, cangrelor significantly reduced periprocedural and 30-day ischemic events in patients undergoing percutaneous coronary intervention (PCI), including IPST.
Methods An independent core laboratory blinded to treatment assignment performed a frame-by-frame angiographic analysis in 10,939 patients for the development of IPST, defined as new or worsening thrombus related to stent deployment at any time during the procedure. Adverse events were adjudicated by an independent, blinded clinical events committee.
Results IPST developed in 89 patients (0.8%), including 35 of 5,470 (0.6%) and 54 of 5,469 (1.0%) patients in the cangrelor and clopidogrel arms, respectively (odds ratio: 0.65; 95% confidence interval: 0.42 to 0.99; p = 0.04). Compared to patients without IPST, IPST was associated with a marked increase in composite ischemia (death, myocardial infarction [MI], ischemia-driven revascularization, or new-onset out-of-laboratory stent thrombosis [Academic Research Consortium]) at 48 h and at 30 days (29.2% vs. 4.5% and 31.5% vs. 5.7%, respectively; p < 0.0001 for both). After controlling for potential confounders, IPST remained a strong predictor of all adverse ischemic events at both time points.
Conclusions In the large-scale CHAMPION PHOENIX trial, the occurrence of IPST was strongly predictive of subsequent adverse cardiovascular events. The potent intravenous adenosine diphosphate antagonist cangrelor substantially reduced IPST, contributing to its beneficial effects at 48 h and 30 days. (Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX]; NCT01156571)
A full list of the investigators can be found in Bhatt DL, Stone GW, Mahaffey KW, et al. N Engl J Med 2013;368:1303–13. The CHAMPION-PHOENIX trial was funded by The Medicines Company and designed collaboratively by the Executive Committee and the sponsor. The present analysis was externally validated by the Harvard Clinical Research Institute, Dr. Généreux has received speaker fees from Abbott Vascular. Dr. Stone has served as a consultant to Boston Scientific, Eli Lilly, Daiichi Sankyo Company, Inc., and AstraZeneca. Dr. Harrington is a consultant for Baxter, Bristol-Myers Squibb Company, CSL Behring, Daiichi-Lilly, Gilead, Johnson & Johnson Corporation, Janssen Pharmaceuticals, Merck, MyoKardia, and WebMD; and has received research grants/contracts from AstraZeneca, Bristol-Myers Squibb, CSL, GlaxoSmithKline, Merck, Portola, Regado, sanofi-aventis, and The Medicines Company. Dr. Gibson has received research grants from Angel Medical Corporation, Atrium Medical Systems, Bayer Corporation, Bristol-Myers Squibb Company, Ikaria, Inc., Janssen Pharmaceuticals, Johnson & Johnson Corporation, Lantheus Medical Imaging, Medtronic Vascular, Inc., Portola Pharmaceuticals, Stealth Peptides, Inc., St. Jude Medical, Volcano Corp, and Walk Vascular; and has received consultant's fees from Atrium Medical Systems, Baxter Healthcare, Boehringer Ingelheim, Bristol-Myers Squibb Company, Cardiovascular Research Foundation, CSL Behring, Cytori Therapeutics, Daiichi Sankyo Company, Inc., Eli Lilly & Company, Exeter Group, Google, Inc., Navigant, St. Jude Medical, The Medicines Company, and WebMD. Dr. Steg has received research grants (to INSERM U698) from the NYU School of Medicine, sanofi-aventis, and Servier; speaker's or consultant's honoraria from Amarin, AstraZeneca, Bayer Corporation, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Iroko Cardio, Lilly, Medtronic, Novartis, Otsuka, Pfizer, Roche, sanofi-aventis, Servier, The Medicines Company, and Vivus; and holds stock options in Aterovax. Dr. Angiolillo has received consultant's fees or honoraria from Bristol-Myers Squibb, sanofi-aventis, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Merck, Evolva, Abbott Vascular, and PLx Pharma; is involved in participation in review activities from Johnson & Johnson, St. Jude Medical, and Sunovion; has received institutional payments for grants from Bristol-Myers Squibb, sanofi-aventis, GlaxoSmithKline, Otsuka, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, and Evolva; and has other financial relationships with Esther and King Biomedical Research Grant. Dr. Price has received consultant's honoraria from AstraZeneca, Daiichi Sankyo-Lilly, Medicure, The Medicines Company, Janssen Pharmaceuticals, Boston Scientific, Terumo Corporation, and St. Jude Medical; and speaker's honoraria from AstraZeneca and Daiichi Sankyo-Lilly. Dr. Hamm has been a member of the advisory boards of AstraZeneca, Boehringer Ingelheim, and Merck, Sharp, & Dohme; and has received speaker's honoraria from The Medicines Company, AstraZeneca, Daiichi Sankyo, Bayer, Boehringer Mannheim, sanofi-aventis, Bristol-Myers Squibb, and Pfizer. Dr. Mahaffey has received consultant's honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Merck, Ortho/McNeill, Pfizer, and Polymedix; and has received institutional research grants from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Merck, Portola, Regado Biotechnologies, sanofi-aventis, Schering-Plough (now Merck), and The Medicines Company. Dr. Bhatt has been a member of the advisory boards of Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; is a member of the board of directors of Boston VA Research Institute and the Society of Cardiovascular Patient Care; is the chair of the American Heart Association Get With The Guidelines Steering Committee; has received honoraria from the American College of Cardiology (Editor, Clinical Trials, Cardiosource), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), WebMD (CME steering committees); is the editor of the Journal of Invasive Cardiology; is a member of data monitoring committees for Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and the Population Health Research Institute, has received research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Roche, sanofi-aventis, and The Medicines Company (for his role as the co-chair of the CHAMPION PCI, PLATFORM, and PHOENIX trials); and has been involved in unfunded research for FlowCo, PLx Pharma, and Takeda. All other authors have reported that they have no other relationships relevant to the contents of this paper to disclose.
- Received October 14, 2013.
- Revision received October 22, 2013.
- Accepted October 22, 2013.
- 2014 American College of Cardiology Foundation