Early and Sustained Dual Oral Antiplatelet Therapy Following Percutaneous Coronary Intervention
Topic: Antiplatelets in acute coronary syndrome
- Determine optimal duration of dual anti platelet therapy and determine the benefit of preprocedural loading dose of clopidogrel.
- Prospective, multi-centered, double blinded, randomized clinical trial
- Clopidogrel 300 mg and aspirin 325 mg oral loading 3 to 24 hours prior to PCI, then clopidogrel (75 mg) and aspirin (325 mg) through day 28, then clopidogrel (75 mg) and aspirin (81-325 mg) for 12 months.
- Placebo and aspirin (dose noted above) oral loading 3 to 24 hours prior to PCI, then placebo and aspirin (81-325 mg) for 12 months.
- 2,116 patients
- 21 years and older with symptomatic coronary artery disease (symptoms of angina, positive stress test results, or dynamic ECG changes)
- Referred for PCI
- Thought to be high likelihood for requiring PCI
- Contraindications to antithrombotic/antiplatelet therapy
- > 50% stenosis of LAD
- Failed PCI within 2 weeks
- Coronary anatomy not amenable for stenting
- Persistent ST elevation within 24 hours of randomization
- Planned staged interventional procedure
- Administration of GpIIb-IIIa within 7 days, clopidogrel within 10 days, or thrombolytics within 24 hours
- 12 months
- At 1 year: composite of death, MI, and stroke in the intent-to-treat population; at 28 days: composite of death, MI, or urgent target vessel revascularization.
- Individual components of the composite end points, administration of clopidogrel less than 6 hours or at least 6 hours before PCI, target vessel revascularization or any revascularization at 1 year, and bleeding.
- Mean age 61, 28.5% were women.
- 74.9% had unstable angina, 26.1% had NSTEMI.
- Clopidogrel loading dose was associated with a nonsignificant 18.5% relative reduction in the combined end point of death, MI, or urgent target vessel revascularization at 28 days compared to placebo (6.8% vs 8.3%; CI, −14.2% to 41.8%; P = 0.23).
- Among patient who received clopidogrel at least 6 hours prior to PCI, there was a 38.6%relative reduction in the combined end point, compared to placebo (CI, −1.6% to 62.9%; P = 0.051).
- Patients who received a GpIIb-IIIa antagonist with clopidogrel pretreatment, there was a 30% relative reduction in events compared to GpIIb-IIIa with placebo (7.3% vs 10.3%; P = 0.12), and influenced by timing of pretreatment.
- No difference in bleeding between groups, except in patients who received GpIIb-IIIa with clopidogrel loading (non significant increase in minor bleeding).
- At 12 months, long-term treatment was associated with a 26.9% reduction in the relative risk of the combined end point of death, MI, and stroke (CI, 3.9%-44.4%; P = 0.02), with a trend towards increase in major bleeding (8.8% clopidogrel vs 6.7% placebo; P = 0.07).
TAKE AWAY: 12 months of dual antiplatelet therapy lead to a significant reduction in atherothrombotic events compared to treatment for 4 weeks. Clopidogrel loading at least 6 hours prior to PCI led to significantly less periprocedural major adverse cardiac events, with or without concomitant use of GpIIb-IIIa inhibitor.
Reference: Steinhubl SR, Berger PB, Mann JT 3rd, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;288(19):2411-20.