Author + information
- Received September 15, 2014
- Revision received October 21, 2014
- Accepted November 6, 2014
- Published online January 1, 2015.
- Peter Clemmensen, MD, DMSc∗∗ (, )
- Sebastian Wiberg, MD†,
- Arnoud van't Hof, MD, PhD‡,
- Efthymios N. Deliargyris, MD§,
- Pierre Coste, MD‖,
- Jurrien ten Berg, MD¶,
- Claudio Cavallini, MD#,
- Martial Hamon, MD∗∗,
- Dariusz Dudek, MD††,
- Uwe Zeymer, MD‡‡,
- Xavier Tabone, MD§§,
- Steen D. Kristensen, MD, DMSc‖‖,
- Debra Bernstein, PhD§,
- Prodromos Anthopoulos, MD§,
- Jayne Prats, PhD§ and
- Philippe Gabriel Steg, MD¶¶,##∗∗∗,†††
- ∗Department of Medicine, Division of Cardiology, Nykoebing F Hospital Nykoebing, Denmark
- †Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- ‡Department of Cardiology, Isala Klinieken, Zwolle, the Netherlands
- §The Medicines Company, Parsippany, New Jersey
- ‖Hôpital Cardiologique–Centre Hospitalier Universitaire Bordeaux, Université de Bordeaux, Pessac, France
- ¶St. Antonius Hospital, Nieuwegein, the Netherlands
- #Ospedale Santa Maria della Misericordia di Perugia, Perugia, Italy
- ∗∗Clinical Research Department, University of Caen, Caen, France
- ††Department of Cardiology and Cardio Vascular Interventions, University Hospital, Jagiellonian University, Krakow, Poland
- ‡‡Klinikum Ludwigshafen, Ludwigshafen, Germany
- §§Hôpital de Bourges, Bourges, France
- ‖‖Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
- ¶¶Université Paris-Diderot, Sorbonne Paris-Cité, Paris, France
- ##Cardiology, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France
- ∗∗∗Institut National de la Santé et de la Recherche Médicale U1148, Paris, France
- †††National Heart and Lung Institute, Imperial College, Imperial College School of Medicine, Royal Brompton Hospital, London, United Kingdom
- ↵∗Reprint requests and correspondence:
Dr. Peter Clemmensen, Division of Cardiology/Department of Medicine, Nykoebing F Hospital, Fjordvej 15, DK-4800 Nykoebing, Denmark.
Objectives This study sought to determine clinical, procedural, and treatment factors associated with acute stent thrombosis (AST) in the EUROMAX (European Ambulance Acute Coronary Syndrome Angiography) trial.
Background Bivalirudin started during transport for primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction significantly reduced major bleeding compared with heparin with or without glycoprotein IIb/IIIa inhibitors (GPI), but it was associated with an increase in AST.
Methods We compared patients with (n = 12) or without AST (n = 2,184) regarding baseline, clinical, and procedural characteristics and antithrombotic treatment strategies (choice of P2Y12 inhibitor, post–primary PCI bivalirudin infusion dose [0.25 mg/kg/h, or BIV-LOW] vs. [1.75 mg/kg/h, or BIV-PCI] vs. heparin ± GPI). Logistic regression was performed to identify independent correlates of AST.
Results The overall AST rate was 0.6% and was higher with bivalirudin than with heparin ± GPI (1.1% vs. 0.2%; p = 0.007). Median time to AST was 2.3 h (interquartile range: 1.9 to 2.8 h). Patients with AST had less hypertension (2 of 14 [14.0%] vs. 961 of 2,182 [44.0%]; p = 0.03), and more frequently received GPI (11 of 14 [78.6%] vs. 880 of 2,183 [40.3%]; p = 0.004). Multivariate analysis using Firth penalized maximum likelihood estimation found hypertension (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.07 to 0.92; p = 0.037) and BIV-LOW (OR: 5.8, 95% CI: 1.5 to 22.2; p = 0.010) predictive of AST. Choice of P2Y12 inhibitor had no impact on AST. Compared with heparin ± GPI, AST rates were higher for BIV-LOW (11 of 670 [1.6%] vs. 2 of 947 [0.2%]; p = 0.008), but not different for BIV-PCI (1 of 244 [0.4%]; p = 0.588).
Conclusions In this post-hoc analysis from EUROMAX, AST occurred very early and was not mitigated by the novel P2Y12 inhibitors. Prolonging the bivalirudin infusion at the PCI dose (but not at a lower dose) appeared to mitigate the risk of AST.
- percutaneous coronary intervention
- stent thrombosis
- ST-segment elevation myocardial infarction
The EUROMAX study was sponsored by The Medicines Company. Dr. Clemmensen has been involved in research contracts with Abbott, AstraZeneca, Aventis, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Pfizer, The Medicines Company, Nycomed, Janssen, Medtronic, Organon, Merck, Myogen, Pharmacia, Regado, Sanofi, Searle, and Servier; has consulted for Evolva, Fibrex, AstraZeneca, Bayer, Boehringer Ingelheim, and Mitsubishi Pharma; and has received speakers fees from Aventis, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Merck, Medtronic, Philips, The Medicines Company, Nycomed, Pfizer, Sanofi, and Servier. Dr. van't Hof has received grant and nonfinancial support from The Medicines Company during the conduction of the study; and grant support from Correvio, AstraZeneca, Eli Lilly, and Medtronic outside the submitted work. Dr. Deliargyris is an employee of The Medicines Company. Dr. Coste has received lectures fees from AstraZeneca, Eli Lilly, Daiichi Sankyo, Servier, and The Medicines Company; and consulting fees from The Medicines Company. Dr. ten Berg has received personal fees from Eli Lilly/Daiichi Sankyo, Merck, and AstraZeneca during the conduction of the study; and speaking fees from The Medicines Company. Dr. Hamon has received personal fees from The Medicines Company and Biotronik. Dr. Dudek has received lecture fees and unrestricted grants for organization of institutional conferences from The Medicines Company. Dr. Zeymer has received research funding from Sanofi, Eli Lilly, Daiichi Sankyo, and Novartis; and is on the advisory boards of AstraZeneca, Boehringer Ingelheim, Bayer, Daiichi Sankyo, Lilly, Iroko, and The Medicines Company. Dr. Kristensen has received lecture fees from AstraZeneca, Bristol Meyers Squibb, Eli Lilly, Pfizer, Sanofi, and The Medicines Company. Drs. Bernstein, Anthopoulos, and Prats are employees of The Medicines Company. Dr. Steg has received honoraria from Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Lilly, Medtronic, Merck-Sharpe-Dohme, Novartis, Otsuka, Pfizer, Roche, Sanofi, The Medicines Company, and Vivus; has received research grants from Servier and Sanofi; and is a stockholder in Aterovax. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received September 15, 2014.
- Revision received October 21, 2014.
- Accepted November 6, 2014.
- 2015 American College of Cardiology Foundation