Author + information
- Received December 16, 2011
- Revision received February 8, 2012
- Accepted February 23, 2012
- Published online July 31, 2012.
- Dirk Sibbing, MD⁎ (, )
- Isabell Bernlochner, MD,
- Stefanie Schulz, MD,
- Steffen Massberg, MD,
- Albert Schömig, MD,
- Julinda Mehilli, MD and
- Adnan Kastrati, MD
- ↵⁎Reprint requests and correspondence:
Dr. Dirk Sibbing, Deutsches Herzzentrum München and 1. Medizinische Klinik rechts der Isar, Technische Universität München, Lazarettstrasse 36, 80636 München, Germany
Objectives The ISAR-REACT 4 (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment-4) platelet substudy aimed to determine the relevance of high on-clopidogrel treatment platelet reactivity (HPR) in non–ST-segment elevation myocardial infarction patients that received abciximab with unfractionated heparin (UFH) or bivalirudin during percutaneous coronary intervention (PCI).
Background In patients undergoing PCI, HPR has been linked to a higher risk for ischemic events. The influence of HPR on clinical outcomes may differ with regard to the adjunctive antithrombotic treatment administered. In ISAR-REACT 4, bivalirudin treatment showed similar efficacy profiles as compared to abciximab with UFH. The impact of HPR on clinical outcomes in abciximab with UFH versus bivalirudin treated non–ST-segment elevation myocardial infarction patients has never been investigated specifically.
Methods A total of 564 patients (274 in abciximab/UFH group vs. 290 in bivalirudin group) were enrolled in this study. Presence or absence of HPR following clopidogrel loading was determined by platelet function testing on a Multiplate analyzer (Verum Diagnostica, Munich, Germany). Per study group and stratified in HPR and no-HPR patients, the 30-day incidence of a combined efficacy endpoint (death, myocardial infarction, urgent target vessel revascularization) was determined.
Results For abciximab with UFH, the incidence of the efficacy endpoint was similar in HPR versus no-HPR patients (9.4% vs. 6.7%; odds ratio: 1.4; 95% confidence interval: 0.6 to 3.5; p = 0.43). For bivalirudin, the incidence of the efficacy endpoint was significantly higher in HPR versus no-HPR patients (22.0% vs. 5.0%; odds ratio: 5.4; 95% confidence interval: 2.4 to 12.1; p < 0.0001).
Conclusions For patients with a risk profile similar to the subjects enrolled in this platelet substudy, the impact of HPR on clinical outcomes may depend on the type of adjunctive antithrombotic therapy used during PCI. Further investigations are warranted to clarify whether assessment of platelet function may help tailoring antithrombotic therapy during PCI. (Randomized Comparison of Abciximab Plus Heparin With Bivalirudin in Acute Coronary Syndrome [ISAR-REACT 4]; NCT00373451)
This work was supported in part by Nycomed Pharma, Unterschleissheim, Germany (former distributor of bivalirudin in Europe), and a grant (KKF 04-06 ) from Deutsches Herzzentrum, Munich, Germany. Material for platelet function testing was in part provided free of charge from Verum Diagnostica. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. Dr. Sibbing has received fees for advisory board activities from Verum Diagnostica and Eli Lilly; and speaker fees from AstraZeneca. Dr. Kastrati has received consulting fees from AstraZeneca, Bristol-Myers Squibb, and Daiichi Sankyo/Eli Lilly and lecture fees from Abbott, Biotronik, Cordis, and Medtronic. Dr. Mehilli has received lecture fees from Abbott, Daiichi Sankyo/Eli Lilly, and Terumo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Sibbing and Bernlochner both contributed equally to this work.
- Received December 16, 2011.
- Revision received February 8, 2012.
- Accepted February 23, 2012.
- American College of Cardiology Foundation