Clopidogrel With Eptifibatide to Arrest the Reactivity of Platelets - CLEAR PLATELETS-2


The goal of the trial was to evaluate platelet reactivity and clot strength following combination therapy with bivalirudin and eptifibatide compared with bivalirudin alone in patients undergoing elective percutaneous coronary intervention (PCI), and to determine whether these variables were related to periprocedural infarction.


Combination therapy with bivalirudin and eptifibatide during elective PCI would be more effective in inhibiting platelet reactivity and clot strength and preventing periprocedural infarction.

Study Design

Study Design:

Patients Enrolled: 200
Mean Follow Up: 6 months
Mean Patient Age: 64 years
Female: 39%

Patient Populations:

  • Age 18 or older
  • Stable patients undergoing elective PCI


  • History of bleeding diathesis, acute myocardial infarction within 48 hours
  • Elevated cardiac markers
  • Cerebrovascular event within 3 months
  • Chronic vessel occlusion
  • Visible thrombus
  • Illicit drug or alcohol abuse
  • Prothrombin time >1.5 times control
  • Platelet count <100,000/mm3
  • Hematocrit <30%
  • Creatinine >2.0 mg/dl
  • Anticoagulation therapy or glycoprotein IIb/IIIa inhibitor use prior to the procedure

Primary Endpoints:

  • Platelet reactivity, measured by turbidometric aggregometry
  • TIP-FCS, measured by thrombelastography

Secondary Endpoints:

  • Relationship between platelet reactivity, TIP-FCS, and periprocedural myocardial infarction

Drug/Procedures Used:

Patients with coronary artery disease undergoing elective PCI were stratified according to clopidogrel therapy before PCI and randomized to treatment with bivalirudin (n = 102) or bivalirudin + eptifibatide (n = 98). Clopidogrel-naïve patients (n = 128) were treated with a 600 mg loading dose of clopidogrel immediately following PCI, whereas patients taking clopidogrel prior to PCI (n = 72) received no additional loading dose.

Concomitant Medications:

All patients were treated with aspirin 325 mg daily. For the four groups, bivalirudin + 600 mg clopidogrel, bivalirudin + 600 mg clopidogrel + eptifibatide, bivalirudin + 75 mg clopidogrel, bivalirudin + 75 mg clopidogrel + eptifibatide: beta-blockers (53%, 58%, 67%, 75%), angiotensin-converting enzyme inhibitors (48%, 31%, 50%, 78%), calcium channel blockers (18%, 16%, 36%, 17%), lipid-lowering agents (77%, 70%, 76%, 81%)

Principal Findings:

Platelet inhibition, as measured by 15 and 25 µM thrombin receptor activator peptide-induced, 5 and 20 µM adenosine diphosphate-induced, and collagen-induced aggregation, was significantly greater at 2, 6-8, and 18 hours after PCI in patients treated with bivalirudin + eptifibatide in combination (p < 0.001 for all comparisons). This effect was present in both the clopidogrel-naïve and clopidogrel maintenance therapy groups. Furthermore, there was significantly lower overall thrombin-induced platelet-fibrin clot strength (TIP-FCS) in patients treated with bivalirudin and eptifibatide in combination (p < 0.001) in both clopidogrel-naïve and clopidogrel maintenance groups.

Peak biomarker release (creatine kinase-myocardial band [CK-MB], troponin-I, and myoglobin) was significantly lower in clopidogrel-naïve patients treated with bivalirudin + eptifibatide combination therapy (p < 0.05 for all comparisons). Furthermore, the incidence of periprocedural myocardial infarction was significantly lower in patients treated with bivalirudin + eptifibatide combination therapy regardless of clopidogrel status. Patients with periprocedural myocardial infarction measured by CK-MB had significantly higher mean TIP-FCS and platelet reactivity.


The results from the CLEAR PLATELETS-2 study suggest that the relationship between platelet reactivity, clot strength, and periprocedural myocardial infarction may be important in patients undergoing PCI. In the future, measures of platelet reactivity and clot strength may be helpful in identifying a subgroup of patients who may benefit from glycoprotein IIb/IIIa therapy during elective PCI; however, this concept will need to be evaluated in large-scale randomized clinical trials.


Gurbel PA, Bliden KP, Saucedo JF, et al. 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. J Am Coll Cardiol 2009;53:648-57.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Novel Agents, Interventions and Coronary Artery Disease

Keywords: Coronary Artery Disease, Myocardial Infarction, Thrombin, Platelet Aggregation Inhibitors, Myoglobin, Creatine Kinase, MB Form, Receptors, Thrombin, Ticlopidine, Blood Platelets, Hirudins, Stents, Percutaneous Coronary Intervention, Troponin I, Peptides, Recombinant Proteins, Peptide Fragments, Fibrin, Collagen, Platelet Glycoprotein GPIIb-IIIa Complex

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