Clopidogrel Dose in Non-ST Elevation Acute Coronary Syndrome Stenting Patients - Clopidogrel Dose in Non-ST Elevation Acute Coronary Syndrome Stenting Patients

Description:

The goal of the trial was to compare 300 mg versus 600 mg of clopidogrel loading dose among patients with non-ST elevation acute coronary syndrome (NSTE ACS) undergoing stenting.

Study Design

Study Design:

Patients Enrolled: 292
Mean Follow Up: 30 days
Mean Patient Age: Mean age 65 years
Female: 24

Patient Populations:

Consecutive patients at a single center with NSTE ACS scheduled for PCI within 48 hours. NSTE ACS was defined as clinical symptoms compatible with acute myocardial ischemia within 12 hours before admission and at least one of the following: a new finding of ST-segment depression >0.05 mV; transient ST-segment elevation >0.1 mV; T-wave inversion >0.3 mV in at least two leads; and elevated levels of cardiac markers or coronary disease as documented by a history of catheterization, revascularization, or myocardial infarction.

Exclusions:

History of bleeding diathesis, persistent STE ACS, New York Heart Association functional class IV, PCI or coronary bypass grafting <3 months, contraindications to antiplatelet therapy, platelet count <100,000, creatinine clearance <25 ml/min, and use of glycoprotein IIb/IIIa inhibitors before the procedure

Drug/Procedures Used:

Consecutive patients with NSTE ACS at a single center were randomized to receive a loading dose of clopidogrel of either 300 mg (n = 146) or 600 mg (n = 146) at least 12 hours prior to percutaneous coronary intervention (PCI) with stenting. A blood sample was drawn prior to PCI to measure adenosine diphosphate (ADP)-induced platelet aggregation and platelet surface expression of P-selectin.

Concomitant Medications:

Aspirin (250 mg load and 160 mg daily); post-PCI clopidogrel 75 mg daily

Principal Findings:

Of the 387 patients initially randomized into the study, 95 were excluded due to: 1) medical management rather than PCI (n = 72); 2) bypass surgery rather than PCI (n = 20); and 3) failed PCI (n = 3). Of the 292 patients in the analysis, 23% had a positive troponin and 23% had ST-segment changes. Tirofiban was given in 34% of patients. Anticoagulant used was low molecular weight heparin in 66% of patients.

The 600 mg clopidogrel group had lower mean maximal intensity of ADP-induced platelet aggregation compared with the 300 mg group (50% vs. 61%, p < 0.0001). High post-treatment platelet reactivity (HPPR), defined as platelet aggregation >70%, was less common in the 600 mg group (15% vs. 25%, p = 0.04). P-selectin was also lower in the 600 mg group compared with the 300 mg group (mean 0.38 vs. 0.60, p < 0.0001).

By 30 days, recurrent cardiovascular events had occurred less frequently in the 600 mg group than the 300 mg group (5% vs. 12%, p = 0.02). Presence of HPPR was associated with recurrence of cardiovascular events: Of the 18 events in the 300 mg group, 12 had HPPR (67%); of the seven events in the 600 mg group, six had HPPR (86%). There were no major bleeding events or transfusions.

Interpretation:

Among patients with NSTE ACS undergoing stenting, use of a 600 mg clopidogrel loading dose was associated with reduced platelet aggregation immediately prior to PCI compared with a 300 mg loading dose. Additionally, recurrent cardiovascular events at 30 days were lower in the 600 mg group.

The findings of the present study extend results seen in the CLEAR-PLATELETS and ALBION trials, which both showed improvements in platelet aggregation with higher clopidogrel loading dose, but were conducted in patients undergoing elective coronary stenting rather than stenting for NSTE ACS. A novel finding of the present study is the relation between high post-treatment platelet reactivity (i.e., platelet aggregation >70%) prior to PCI and subsequent cardiovascular events by 30 days. These data suggest patients without adequate platelet aggregation, often called clopidogrel nonresponders, are at higher risk of clinical events. More potent P2Y12 inhibitors, which may reduce the number of nonresponders, are currently being studied in ongoing randomized trials.

References:

Cuisset T, Frere C, Quilici J, et al. Benefit of a 600-mg loading dose of clopidogrel on platelet reactivity and clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing coronary stenting. J Am Coll Cardiol 2006;48:1339-45.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, ACS and Cardiac Biomarkers, Anticoagulation Management and ACS, Heart Failure and Cardiac Biomarkers, Interventions and ACS

Keywords: Acute Coronary Syndrome, Myocardial Infarction, Platelet Aggregation Inhibitors, Heparin, Low-Molecular-Weight, Coronary Disease, Ticlopidine, Tyrosine, Percutaneous Coronary Intervention, P-Selectin, Platelet Aggregation, Catheterization, Troponin


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