Randomized Argentine Clopidogrel Stent Trial - RACS

Description:

The goal of the trial was to evaluate short-term (30 days) with longer-term (180 days) treatment with clopidogrel among patients undergoing percutaneous coronary intervention (PCI) with bare-metal stenting.

Study Design

Study Design:

Patients Screened: 10,344
Patients Enrolled: 1,004
Mean Follow Up: 6 months
Mean Patient Age: Mean age 61 years
Female: 20

Patient Populations:

Age ≥18 years; symptomatic coronary artery disease with objective evidence of ischemia; target lesion with ≥50% stenosis by visual estimation in a native coronary artery >2.5 mm; and successful PCI procedure with placement of ≥1 stent without evident complications in the previous 24 hours

Exclusions:

Allergy or contraindication to aspirin or clopidogrel; long-term clopidogrel therapy; nonsteroidal anti-inflammatory agents other than aspirin within the previous 7 days; receipt of a glycoprotein IIb/IIIa inhibitor within the previous 7 days; target in-stent restenosis or vein graft lesion; stroke or transient ischemic attack within the previous 12 months; a coagulation disorder; refusal to receive a blood transfusion if needed; major bleeding within previous 6 months; life expectancy <1 year; enrollment in another study; need for warfarin; or a revascularization procedure performed (PCI or coronary artery bypass grafting) within the previous 3 months

Primary Endpoints:

Composite of death, MI, or stroke at 180 days

Secondary Endpoints:

Composite of death, MI, stroke, or target vessel revascularization at 6 months

Drug/Procedures Used:

Following successful PCI with bare-metal stenting and a 300 mg load of clopidogrel, patients were randomized in an open-label manner to treatment with clopidogrel for 30 days (short-term; n = 502) or for 180 days (long-term; n = 502). The trial was conducted at 18 sites in Argentina.

Concomitant Medications:

Aspirin

Principal Findings:

Glycoprotein IIb/IIIa inhibitors were used in 17% of patients, 90% of which was for bailout use. Mean duration of clopidogrel treatment prior to PCI was 3.3 hours.

The primary composite endpoint of death, myocardial infarction (MI), or stroke by 180 days was lower in the long-term clopidogrel treatment group compared with the short-term treatment group (1.7% vs. 5.0%, p = 0.010). The secondary endpoint of death, MI, stroke, or target vessel revascularization trended lower in the long-term therapy group (5.4% vs. 8.7%, p = 0.054).

Total bleeding occurred in 1.52% of the long-term group and 0.64% of the short-term group (p = 0.34). Clopidogrel was discontinued early by 2.4% of the long-term group and 1.1% of the short-term group.

Interpretation:

Among patients undergoing PCI with bare-metal stenting for symptomatic coronary artery disease with ischemia, treatment with clopidogrel for 180 days was associated with a reduction in the primary endpoint of death, MI, or stroke at 180 days compared with clopidogrel therapy for 30 days.

Results of the present study confirmed earlier observations of the CREDO trial, which showed a trend toward a lower event rate associated with longer-term clopidogrel use after PCI compared with short-term use. However, CREDO had several confounding factors, which prevented definitive conclusions on the effect of the duration versus the dosing. In CREDO, the long-term therapy group received a 300 mg loading dose of clopidogrel ≥3 hours prior to PCI while the short-term groups did not receive a loading dose and only received 75 mg of clopidogrel following the PCI, thus leaving open the question of whether the benefit observed was due to the long duration of therapy or due to the use of a loading dose.

It should be noted that the present study enrolled only patients treated with bare-metal stents; drug-eluting stents may require a much longer duration of therapy due to the increased and continual risk of stent thrombosis, although data are limited on the optimal duration.

References:

Bernardi V, Szarfer J, Summay G, et al. Long-term versus short-term clopidogrel therapy in patients undergoing coronary stenting (from the Randomized Argentine Clopidogrel Stent [RACS] trial). Am J Cardiol 2007;99:349-52.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Interventions and Coronary Artery Disease

Keywords: Stroke, Myocardial Infarction, Coronary Artery Disease, Platelet Aggregation Inhibitors, Drug-Eluting Stents, Ticlopidine, Constriction, Pathologic, Purinergic P2Y Receptor Antagonists, Percutaneous Coronary Intervention, Metals, Thrombosis


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