The goal of the trial was to evaluate treatment with dual antiplatelet therapy with aspirin and clopidogrel compared with triple antiplatelet therapy with aspirin, clopidogrel, and the glycoprotein (GP) IIb/IIIa inhibitor tirofiban among patients with non-ST elevation myocardial infarction (NSTEMI) undergoing angiography with or without revascularization.

Study Design

Study Design:

Patients Screened: 448
Patients Enrolled: 328
Mean Follow Up: 30 days
Mean Patient Age: Mean age 64 years
Female: 29

Patient Populations:

Ischemic chest pain at rest within 24 hours and either positive biomarkers (CK-MB or troponin) or an abnormal ECG (ST depression >0.1 mV in ≥2 leads or transient ST elevation)


Age >80 years, persistent ST elevation, cardiogenic shock, noncardiac ischemia, PCI within the prior six months, renal failure, or concomitant use of a GP IIb/IIIa inhibitor

Primary Endpoints:

Infarct size as assessed by LDHQ at 48 hours and as assessed by peak CK

Secondary Endpoints:

Initial TIMI flow grade of the culprit artery

Drug/Procedures Used:

Patients with NSTEMI scheduled for angiography were randomized to a dual antiplatelet strategy with aspirin and higher-dose clopidogrel (600 mg; n = 166) or a triple antiplatelet strategy with aspirin, standard-dose clopidogrel (300 mg), and tirofiban (10 µg/kg bolus followed by 0.15 µg/kg/min infusion; n = 162). Patients were to undergo angiography in 24-48 hours with or without revascularization.

Concomitant Medications:

All patients were to receive low molecular weight heparin, beta-blocker, and statin therapy.

Principal Findings:

Patients were high-risk per the protocol design, with a positive troponin in 78% and ST depression in 612%. Median time to angiography was 23 hours. Percutaneous coronary intervention (PCI) was performed in 59% of patients.

The primary endpoint of infarct size did not differ between the dual therapy group and the triple therapy group when assessed by LDHQ (193 IU/L for dual therapy vs. 166 IU/L for triple therapy, p = 0.2), peak creatine kinase (CK) (262 vs. 216 IU/L, p = 0.3), or peak CK-MB (33 vs. 27 IU/L, p = 0.2). The secondary endpoint of initial TIMI flow grade 3 at angiography was higher in the triple therapy group (67% vs. 47%, p = 0.002).

There was a trend toward lower rates of death or MI at 30 days in the triple therapy group (46% vs. 57%, p = 0.052), driven almost exclusively by MI (46% vs. 56%) with a mortality rate of only 1% in each group. There was no difference in bleeding between the groups (12% for triple therapy and 10% for dual therapy) and there were no strokes in either arm.


Among patients with NSTEMI undergoing angiography with or without revascularization, use of a triple antiplatelet regimen of aspirin, 300 mg clopidogrel, and tirofiban was not associated with a difference in the primary endpoint of enzymatic infarct size compared with a dual antiplatelet regimen of aspirin and 600 mg clopidogrel.

Although the primary endpoint was not different, the secondary endpoint of initial TIMI grade 3 flow was improved in the triple therapy group. Additionally, there was a favorable trend toward lower rates of MI through 30 days, although the MI rate was very high, suggesting a low-threshold definition of MI was used.

As was shown in the CLEAR PLATELET trial, use of 600 mg clopidogrel results in more rapid platelet inhibition compared with 300 mg of clopidogrel, although neither produced as rapid or potent inhibition as clopidogrel combined with the GP IIb/IIIa inhibitor eptifibatide.

The present trial sheds some light on the clinical implications of the use of these three antiplatelet agents together on clinical outcomes. The much larger ISAR-REACT 2 trial recently demonstrated a reduction in death, MI, or urgent target vessel revascularization by 30 days with triple antiplatelet therapy with abciximab compared with aspirin and clopidogrel alone. It should be noted that current guidelines recommend the use of clopidogrel and a GP IIb/IIIa inhibitor in the setting of high-risk NSTEMI patients planned for PCI.


Rasoul S, Ottervanger JP, de Boer MJ, et al. A comparison of dual vs. triple antiplatelet therapy in patients with non-ST-segment elevation acute coronary syndrome: results of the ELISA-2 trial. Eur Heart J 2006;27:1401-7.

Presented by Dr. Saman Rasoul at the European Society of Cardiology Hot Line Session, September 2005.

Clinical Topics: Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Heart Failure and Cardiac Biomarkers

Keywords: Myocardial Infarction, Stroke, Creatine Kinase, Platelet Aggregation Inhibitors, Coronary Disease, Ticlopidine, Blood Platelets, Electrocardiography, Immunoglobulin Fab Fragments, Tyrosine, Platelet Membrane Glycoprotein IIb, Percutaneous Coronary Intervention, Chest Pain, Troponin

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