Prognostic value of a high on-clopidogrel treatment platelet reactivity in bivalirudin versus abciximab treated non-ST-segment elevation myocardial infarction patients. ISAR-REACT 4 (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment-4) platelet substudy.
OBJECTIVE
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.
Deutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Lazarettstrasse36, Munich, Germany. dirk@sibbing.net
Dirk
D
Sibbing
Isabell
I
Bernlochner
Stefanie
S
Schulz
Steffen
S
Massberg
Albert
A
Schömig
Julinda
J
Mehilli
Adnan
A
Kastrati
D000077284:Abciximab; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D000991:Antithrombins / Q000009:adverse effects / Q000627:therapeutic use*; D000077144:Clopidogrel; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006629:Hirudins / Q000009:adverse effects; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000401:mortality / Q000628:therapy*; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011379:Prognosis; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012815:Signal Processing, Computer-Assisted; D015607:Stents; D016019:Survival Analysis; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D000991:Antithrombins; D006629:Hirudins; D007140:Immunoglobulin Fab Fragments; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D006493:Heparin; D000077144:Clopidogrel; D013988:Ticlopidine; C074619:bivalirudin; D000077284:Abciximab