Thrombolysis With Recombinant Human Tissue-Type Plasminogen Activator During Instability in Coronary Artery Disease: Effect on Myocardial Ischemia and Need for Coronary Revascularization - TRIC


TRIC was a prospective, randomized, double-blind, placebo-controlled, multicenter trial conducted in Sweden to determine the effect of recombinant tissue-type plasminogen activator (rTPA) in patients with unstable angina and non-Q-wave myocardial infarctions (NQWMIs).


Use of rTPA will be associated with improved clinical outcomes compared with placebo in patients with unstable angina and NQWMI.

Study Design

Study Design:

Patients Screened: 2,807
Patients Enrolled: 205
Mean Follow Up: One year
Mean Patient Age: 40-70
Female: 0

Patient Populations:

Men aged 40-70 years admitted to a coronary care unit with ongoing chest pain or anginal chest pain during the preceding 48 hours. The chest pain had to be associated with new or previously unknown ST depression ≥0.1 mV or T-wave inversion >0.1 mV in at least two adjacent leads on the ECG.


Women, increased risk of bleeding, contraindication to thrombolysis, acute QWMI, previous QWMI, previous bypass graft, other heart disease, hemodynamic instability, severe noncardiac disease, hypersensitivity to aspirin or heparin, administrative difficulties, pericarditis, pulmonary embolism, or VOC mitrale

Primary Endpoints:

Occurrence of death, MI, urgent coronary revascularization, or indication for urgent revascularization. Urgent revascularization was defined as revascularization because of refractory angina. Indication for revascularization was defined as signs of myocardial ischemia and three-vessel disease, left main stenosis, or proximal left anterior descending stenosis as part of two-vessel disease.

Secondary Endpoints:

Coronary lesions at coronary angiography one month after inclusion, signs of myocardial ischemia during either of two exercise tests, or symptoms of angina during follow-up

Drug/Procedures Used:

Patients were randomized to IV infusion of rTPA (n=105) or placebo (n=100). The total dose of rTPA was 1 mg/kg body weight with a maximal dose of 100 mg. Half the dose was infused over the first hour and the other half over the following three hours. Patients without chest pain at rest and without new ECG changes for two consecutive days underwent stress testing prior to discharge and between 30 and 45 days after enrollment.

Concomitant Medications:

All patients were treated with oral aspirin, 225 mg initially, then 75 mg daily thereafter. All patients received heparin, 5000 IU, as an initial bolus immediately before trial drug infusion.

After randomization, heparin was infused at 1000 IU/h over 36-48 hours. Thereafter, heparin was given as subcutaneous injections of 10,000 IU twice daily for four days.

All patients without contraindications were treated with oral metoprolol and, if needed, with nitrates and calcium channel blockers (specific numbers of patients not reported).

Principal Findings:

Mean time to treatment was 18 hours after the last episode of chest pain. The groups were well matched at baseline in terms of age, diabetes, coronary artery disease history, ECG changes, and CK elevations. At one year, there were no significant differences between groups for death (three patients rTPA vs. three patients placebo, p=NS), myocardial infarction (11 patients rTPA vs. 15 patients placebo, p=NS), urgent revascularization (nine patients rTPA vs. eight patients placebo, p=NS), or indication for urgent revascularization (35 patients rTPA vs. 45 patients placebo, p=NS).

The rate of the primary endpoint, a combination of death, MI, urgent revascularization, or indication for revascularization, was 44% for rTPA and 54% for placebo (p=0.19) at one year. At stress testing before discharge, a high risk response, defined as a combination of ST depressions and low maximal workload, occurred in 58% of rTPA patients versus 77% of placebo patients (p=0.01).

Myocardial ischemia, defined as death, MI, revascularization for refractory angina, or a high risk exercise response, was significantly higher in the placebo group than the rTPA group (80% vs. 62%, p=0.007) at one year. At coronary angiography performed 30-45 days after inclusion, there were no significant differences in number or severity of coronary stenoses.

There were no episodes of cerebral complications or major bleeding in the rTPA arm. Minor bleeding was reported in 21 patients in the rTPA arm, but none in the placebo arm.


Among men with unstable angina or NQWMI, treatment with rTPA was associated with reduced myocardial ischemia during stress testing, but no significant effects on death, MI, or urgent revascularization compared to placebo.


Karlsson J, Berglund U, Bjorkholm A, Ohlsson J, Swahn E, Wallentin L. Thrombolysis with recombinant human tissue-type plasminogen activator during instability in coronary artery disease: effect on myocardial ischemia and need for coronary revascularization. TRIC Study Group. Am Heart J 1992;124:1419-26.

Clinical Topics: Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Lipid Metabolism, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Myocardial Infarction, Coronary Stenosis, Coronary Angiography, Chest Pain, Body Weight, Electrocardiography, Tissue Plasminogen Activator, Diabetes Mellitus

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