Bivalirudin and clopidogrel with and without eptifibatide for elective stenting: effects on platelet function, thrombelastographic indexes, and their relation to periprocedural infarction results of the CLEAR PLATELETS-2 (Clopidogrel with Eptifibatide to Arrest the Reactivity of Platelets) study.
OBJECTIVE
The primary objective of this study was to compare the effect of therapy with bivalirudin alone versus bivalirudin plus eptifibatide on platelet reactivity measured by turbidometric aggregometry and thrombin-induced platelet-fibrin clot strength (TIP-FCS) measured by thrombelastography in percutaneous coronary intervention (PCI) patients. The secondary aim was to study the relation of platelet aggregation and TIP-FCS to the occurrence of periprocedural infarction.


BACKGROUND
Bivalirudin is commonly administered alone to clopidogrel naïve (CN) patients and to patients on maintenance clopidogrel therapy (MT) undergoing elective stenting. The effect of adding eptifibatide to bivalirudin on platelet reactivity (PR) and TIP-FCS, and their relation to periprocedural infarction in these patients are unknown.


METHODS
Patients (n = 200) stratified to clopidogrel treatment status were randomly treated with bivalirudin (n = 102) or bivalirudin plus eptifibatide (n = 98). One hundred twenty-eight CN patients were loaded with 600 mg clopidogrel immediately after stenting, and 72 MT patients were not loaded. The PR, TIP-FCS, and myonecrosis markers were serially determined.


RESULTS
In CN and MT patients, bivalirudin plus eptifibatide was associated with markedly lower PR at all times (5- and 20-microM adenosine diphosphate-induced, and 15- and 25-microM thrombin receptor activator peptide-induced aggregation; p < 0.001 for all) and reduced mean TIP-FCS (p < 0.05). Patients who had a periprocedural infarction had higher mean 18-h PR (p < 0.0001) and TIP-FCS (p = 0.002).


CONCLUSIONS
For elective stenting, the addition of eptifibatide to bivalirudin lowered PR to multiple agonists and the tensile strength of the TIP-FCS, 2 measurements strongly associated with periprocedural myonecrosis. Future studies of PR and TIP-FCS for elective stenting may facilitate personalized antiplatelet therapy and enhance the selection of patients for glycoprotein IIb/IIIa blockade. (Peri-Procedural Myocardial Infarction, Platelet Reactivity, Thrombin Generation, and Clot Strength: Differential Effects of Eptifibatide + Bivalirudin Versus Bivalirudin [CLEAR PLATELETS-2]; NCT00370045.
Gurbel
Paul A
PA
Sinai Center for Thrombosis Research, 2401 West Belvedere Avenue, Baltimore, MD 21215, USA. pgurbel@lifebridgehealth.org
Bliden
Kevin P
KP
Saucedo
Jorge F
JF
Suarez
Thomas A
TA
DiChiara
Joseph
J
Antonino
Mark J
MJ
Mahla
Elisabeth
E
Singla
Anand
A
Herzog
William R
WR
Bassi
Ashwani K
AK
Hennebry
Thomas A
TA
Gesheff
Tania B
TB
Tantry
Udaya S
US
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000925:Anticoagulants / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D003094:Collagen / Q000494:pharmacology; D004359:Drug Therapy, Combination; D000077542:Eptifibatide; D005260:Female; D018056:Hemorheology; D006629:Hirudins / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D010446:Peptide Fragments / Q000008:administration & dosage*; D010455:Peptides / Q000008:administration & dosage*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D018179:Receptors, Thrombin / Q000502:physiology; D011994:Recombinant Proteins / Q000008:administration & dosage; D015607:Stents; D013916:Thrombelastography; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000925:Anticoagulants; D006629:Hirudins; D010446:Peptide Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D018179:Receptors, Thrombin; D011994:Recombinant Proteins; D000244:Adenosine Diphosphate; D003094:Collagen; D000077144:Clopidogrel; D000077542:Eptifibatide; D013988:Ticlopidine; C074619:bivalirudin