Randomized Evaluation of Anticoagulation Versus Antiplatelet Therapy After Coronary Stent Implantation in High-Risk Patients: The Multicenter Aspirin and Ticlopidine Trial After Intracoronary Stenting - MATTIS


The goal of the study was to assess the safety and efficacy of dual antiplatelet therapy with ticlopidine and aspirin versus aspirin and oral anticoagulation among high-risk patients after coronary stent implantation.


Because the combination of aspirin and ticlopidine had been shown to be superior to aspirin plus oral anticoagulation after coronary artery stenting in low-risk patients, it was hypothesized that the same would be true for high-risk patients.

Study Design

Study Design:

Patients Enrolled: 350
Mean Follow Up: 30 days
Mean Patient Age: Mean 60.4 ± 9.9 years
Female: 24

Patient Populations:

Patients were eligible to participate in this study if they met at least one of the following criteria after their coronary stenting procedure: bailout stenting for acute vessel closure or dissection, suboptimal stenting result (i.e., >20% residual stenosis within the stent, residual dissection, >30% stenosis immediately proximal or distal to the stent, or reduced flow after stent implantation), ≥3 stents placed within the same vessel, total length of stents ≥45 mm, or maximal nominal balloon diameter used was ≤2.5 mm.


The exclusion criteria included: recent myocardial infarction, persistent ischemia at the time of randomization, age <18 years, pregnancy, difficulties with follow-up, use of glycoprotein (GP) IIb/IIa antagonists in the periprocedure period or the planned use of GP IIb/IIa antagonists during the follow-up period, need for oral anticoagulation, contraindications to any of the study medications, and participation in another study within the prior 30 days.

Primary Endpoints:

The composite primary endpoint was cardiovascular events at 30 days. Cardiovascular events were defined as the occurrence of cardiovascular death, myocardial infarction, or repeat revascularization.

Secondary Endpoints:

The secondary endpoints of this study were major bleeding or vascular complications. These were defined as the need for surgical repair of the vascular access site, bleeding with a subsequent decrease in hemoglobin by ≥4 g/dl, or requiring a transfusion of ≥2 units of blood, or retroperitoneal or intracranial hemorrhage.

Drug/Procedures Used:

Eligible patients were randomized to receive either dual antiplatelet therapy with aspirin and ticlopidine or aspirin and oral anticoagulation therapy in an open-label fashion. Those randomized to the dual antiplatelet therapy group received aspirin 250 mg/day and ticlopidine 250 mg BID, with the entire daily dose of 500 mg given as a single dose on the first day.

Individuals in the aspirin and oral anticoagulation group received aspirin 250 mg/day and oral anticoagulation to a target international normalized ratio (INR) of 2.5 to 3.0. Intravenous heparin was continued until the target INR was achieved in two consecutive measurements separated by ≥24 hours.

Principal Findings:

There was a strong trend toward a reduction in the primary cardiac endpoint in patients in the dual antiplatelet group compared to those receiving aspirin and oral anticoagulation (5.6% vs. 11%; relative risk [RR] 1.9; 95% confidence interval [CI] 0.9 to 4.1; p=0.07). There was a significant reduction in the incidence of major vascular and bleeding complications among patients receiving dual antiplatelet therapy versus those in the aspirin plus oral anticoagulation group (1.7% vs. 6.9%; RR 4.1; 95% CI 1.2-14.3; p=0.02).


Among high-risk patients undergoing coronary artery stenting, dual antiplatelet therapy with aspirin and ticlopidine was associated with a strong trend toward a reduction in the primary endpoint of cardiac events during the 30-day follow-up period compared to patients receiving aspirin and oral anticoagulation therapy. Additionally, dual antiplatelet therapy was associated with a significant reduction in the incidence of major bleeding and vascular complications.

These findings suggest that, in high-risk patients undergoing coronary artery stent implantation, dual antiplatelet therapy with aspirin and ticlopidine is superior to the combination of aspirin and oral anticoagulation.


Urban P, Macaya C, Rupprecht HJ, et al. Randomized evaluation of anticoagulation versus antiplatelet therapy after coronary stent implantation in high-risk patients: the multicenter aspirin and ticlopidine trial after intracoronary stenting (MATTIS). Circulation 1998;98:2126-32.

Keywords: Risk, Follow-Up Studies, Platelet Aggregation Inhibitors, Heparin, Ticlopidine, Constriction, Pathologic, Stents, International Normalized Ratio, Coronary Vessels, Coronary Thrombosis, Confidence Intervals

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