Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis-2 - APRICOT-2

Description:

The goal of the APRICOT-2 trial was to compare the 3 month angiographic rate of reocclusion in patients treated with aspirin alone to patients treated with a combination of coumarin and aspirin following successful fibrinolysis for ST-elevation myocardial infarction.

Hypothesis:

Patients treated with the combination of aspirin and medium intensity coumarin would have lower rates of angiographic reocclusion compared with patients treated with aspirin alone.

Study Design

Study Design:

Patients Enrolled: 308
Mean Follow Up: 3 months
Mean Patient Age: mean 57 years
Female: 19

Patient Populations:

Thrombolytic treatment of suspected acute myocardial infarction within 6 hours of symptom onset; TIMI 3 flow at coronary angiography performed within 48 hours of thrombolytic administration.

Primary Endpoints:

Angiographic evidence of reocclusion, defined as TIMI grade 2 flow or less, at 3 month follow-up.

Secondary Endpoints:

Total angiographic reocclusion (TIMI 0-1 flow) Composite of death, reinfarction, or revascularization Composite of reinfarction or revascularization Bleeding risks.

Drug/Procedures Used:

Patients were treated with thrombolytic therapy and underwent coronary angiography within 48 hours of thrombolytic therapy. Patients with TIMI 3 flow at angiography were treated wtih either 160 mg aspirin initially plus 80 mg aspirin daily or the combination of the same aspirin dose plus coumarin dosed to target INR of 2.0-3.0. Follow-up angiography was scheduled at 3 months.

Principal Findings:

At 3 month follow-up, reocclusion (TIMI flow <3) occurred in 28% of patients treated with aspirin, compared with 15% in the aspirin plus coumarin group (p=0.02; RR 0.55; CI 0.33-0.90). Total occlusion (TIMI 0 to 1 flow) was present in 20% of the aspirin group vs 9% in the combination therapy group (p=0.02; RR 0.46; CI 0.24-0.89). Event free survival from death, reinfarction or revascularization was 66% in the aspirin group and 86% in the combination group (p<0.01). Both reinfarction and revascularization occurred more frequent in the aspirin only group (8% vs 2% for reinfarction, p<0.05; 31% vs 13% for revascularization, p<0.01). TIMI major and minor bleeding was 3% in the aspirin arm compared with 5% in the coumarin and aspirin arm (p=NS).

Interpretation:

Among patients successfully treated with fibrinolysis for ST-elevation myocardial infarction (MI), coumarin as an adjunctive to aspirin therapy was associated with a significant reduction in angiographic reocclusion. Multiple studies have shown in increase in mortality in patients who experience angiographic reocclusion or clinical reinfarction following the initial ST-elevation MI. Patients in the coumarin arm received intravenous heparin for an additional 2.5 days compared with patients in the aspirin alone arm, so it is unknown how much of the benefit was due to the prolonged heparin therpay or the coumarin. The authors suggest the coumarin therapy may have prevented heparin "rebound", since the majority of in-hospital reinfarctions in the aspirin alone group occurred within 24 hours after discontinuation of UFH. Despite the benefit observed in the combination therapy arm, coumarin therapy requires additional monitoring and dose adjustment.

References:

Circulation. 2002;106:659-665. Presented at ESC 2000.

Clinical Topics: Anticoagulation Management, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Thrombolytic Therapy, Myocardial Infarction, Platelet Aggregation Inhibitors, Warfarin, Disease-Free Survival, Coronary Disease, Heparin, Fibrinolytic Agents, Coronary Angiography, Fibrinolysis, Hemorrhage


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