Randomized Multicenter Comparison of Conventional Anticoagulation Versus Antiplatelet Therapy in Unplanned and Elective Coronary Stenting - FANTASTIC

Description:

The goal of this study was to assess the safety and efficacy of dual antiplatelet therapy with aspirin and ticlopidine versus conventional anticoagulation among patients with an optimal result after coronary artery stenting.

Hypothesis:

Because data existed that dual antiplatelet therapy was at least as effective as anticoagulation in selected patients who achieved an optimal result after coronary stent implantation, it was hypothesized that these results could be extrapolated to general clinical practice, including patients who did not achieve an optimal result after coronary artery stenting.

Study Design

Study Design:

Patients Enrolled: 485
Mean Follow Up: Six months
Mean Patient Age: Mean age 60 ± 11 years
Female: 19

Patient Populations:

Individuals with coronary artery disease that required coronary artery stenting were eligible. This included both patients in whom the stenting was planned and those who required stenting as a bailout procedure after balloon angioplasty.

Exclusions:

Patients were excluded if they had known bleeding disorders; a platelet count <150,000; gastrointestinal bleeding, a cerebrovascular accident, intracranial or eye surgery within the six months prior to the stenting procedure; severe hepatic or renal dysfunction; malignant hypertension; angiographic evidence of thrombus at the proposed stent site; history of allergy to aspirin or ticlopidine; history of heparin-related thrombocytopenia; or systemic disease that significantly limited life expectancy.

Primary Endpoints:

Bleeding complications during the six-week follow-up period after stent implantation. Bleeding complications included ecchymoses, hematomas, pseudoaneurysms, intracranial bleeding, gastrointestinal bleeding, intraocular bleeding, macroscopic hematuria, or any bleeding that required a blood transfusion.

Secondary Endpoints:

Acute or subacute stent thrombosis, MACE (death, and Q-wave or non-Q-wave myocardial infarction), and duration of hospital stay

Drug/Procedures Used:

After coronary artery stent implantation, eligible patients were randomized to receive either dual antiplatelet therapy or anticoagulation. Those in the dual antiplatelet therapy group received 500 mg of ticlopidine in the catheterization laboratory and were discharged on ticlopidine 250 mg orally twice daily for six weeks and aspirin 100 mg to 325 mg orally once daily for life.

Patients in the conventional anticoagulation group received an oral anticoagulant while in the catheterization laboratory. Additionally, after hemostasis was achieved post-sheath removal, patients in the anticoagulation group received an intravenous bolus of 2500 IU heparin, followed by heparin infusion of 1000 IU/h, which was titrated to achieve a target activated partial thromboplastin time of 2.0 to 2.5 times the control value.

The oral anticoagulant was adjusted to achieve a stable international normalized ratio (INR) between 2.5 and 3.0. The intravenous heparin was discontinued after the INR was documented to be in the target range for two consecutive days. Patients were continued on the oral anticoagulation for six weeks and aspirin 100 mg to 325 mg orally once daily for life.

Concomitant Medications:

Prior to the coronary artery interventional procedure, at the discretion of the investigator, patients were pretreated with aspirin 100 mg to 300 mg. Additionally, they were given a heparin bolus of 10,000 IU immediately prior to angioplasty and supplemental boluses of 1000 IU every hour until completion of the procedure.

Principal Findings:

The primary endpoint of bleeding complications occurred significantly more frequently among patients in the conventional anticoagulation group than the dual antiplatelet group (21% vs. 13.5%, p=0.03). This difference was principally due to a significant excess of ecchymoses >5 cm in patients receiving conventional anticoagulation (38% vs. 16%, p=0.006).

In the subset of patients undergoing elective stenting, there was a significant reduction in major adverse cardiac events (MACE) among patients treated with dual antiplatelet therapy (2.4% vs. 9.9%, p=0.01). Finally, individuals receiving dual antiplatelet therapy had significantly shorter hospital stays than those receiving conventional anticoagulation (4.3 ± 3.6 vs. 6.4 ± 3.7 days, p=0.0001).

Interpretation:

Among patients with coronary artery disease requiring stent implantation, dual antiplatelet therapy with ticlopidine and aspirin was associated with a reduction in the primary endpoint of bleeding complications at six weeks after stenting, as well as decreased duration of hospitalization postprocedure compared to conventional anticoagulation. Additionally, those patients undergoing elective stenting were less likely to experience MACE during the follow-up period.

These findings suggest that, in patients requiring coronary artery stent implantation, dual antiplatelet therapy is superior to conventional anticoagulation therapy.

References:

Bertrand ME, Legrand V, Boland J, et al. Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The full anticoagulation versus aspirin and ticlopidine (fantastic) study. Circulation 1998;98:1597-603.

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

Keywords: Coronary Artery Disease, Follow-Up Studies, Platelet Aggregation Inhibitors, Heparin, Ticlopidine, Hemostasis, Angioplasty, Balloon, Coronary, Length of Stay, Stents, International Normalized Ratio, Ecchymosis, Partial Thromboplastin Time, Catheterization


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