Multicenter Patency Trial of Intravenous Antistreplase Compared With Streptokinase in Acute Myocardial Infarction - TEAM-2

Description:

TEAM-2 was a prospective, randomized, double-blind, placebo-controlled, multicenter trial of antistreplase versus streptokinase in patients with ST-segment elevation myocardial infarction.

Hypothesis:

Antistreplase will be more effective than streptokinase in producing coronary artery patency in patients with ST-segment elevation myocardial infarction.

Study Design

Study Design:

Patients Enrolled: 370
Mean Follow Up: Hospital Discharge
Mean Patient Age: <76
Female: 22

Patient Populations:

Age <76 years, symptoms of chest pain for more than 30 minutes but less than four hours prior to treatment, ST-segment elevation of 0.1 mV or more in one or more limb leads or 0.2 mV or more in one or more precordial leads, and symptoms not relieved by nitroglycerine

Exclusions:

Cardiogenic shock, history of CABG or PTCA within one month, contraindication to thrombolytic therapy including recent (<6 months) history of thrombotic cerebrovascular accident (CVA) or intracranial or intraspinal surgery, hemorrhagic CVA at any time, active internal bleeding, history of hemorrhagic diathesis, peptic ulcer within six months, long-term full dose anticoagulation with warfarin or Coumadin, external chest massage or other injury for this episode of infarction, other major trauma within 10 days, pregnancy or lactation or childbearing potential, prosthetic heart valves, dilated cardiomyopathy, ventricular aneurysm with thrombus, streptokinase or antistreplase within previous six months, other investigational drug therapy within two months, systolic blood pressure >200 mm Hg, or diastolic blood pressure >120 mm Hg

Primary Endpoints:

Infarct-related vessel patency defined as TIMI 2 or 3 flow at early (90-240 minutes) and late (24 hours) angiography

Secondary Endpoints:

Rates of angioplasty and CABG; adverse events including hypotension, mortality, bleeding complications, and stroke; and residual percent stenosis in the infarct-related vessel and rates of individual TIMI grade flows

Drug/Procedures Used:

Patients were randomized to IV infusion of streptokinase (1.5 million U over 60 minutes) or antistreplase (30 U over 2-5 minutes). Coronary perfusion status was determined early (between 90 minutes and 240 minutes after start of therapy) and late (24 hours) via coronary angiography. For patients with TIMI grade 0, 1, or poor grade 2 flow through the infarct-related vessel, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) was allowed before the 24-hour angiogram at the discretion of the treating physician.

Concomitant Medications:

All patients received heparin (5000-10,000 U bolus at the start of catheterization titrated as continuous infusion to activated partial thromboplastin time twice the upper limit of normal) and continued for at least 24 hours.

Before hospitalization, other therapies for the antistreplase and streptokinase arms, respectively, included nitrates (15% vs. 12%) and beta-blockers (13% vs. 14%). After hospitalization but before thrombolysis, other therapies for the antistreplase and streptokinase arms, respectively, included nitrates (89% vs. 92%) and beta-blockers (4% vs. 5%).

Aspirin use was not reported. Diphenhydramine was recommended, but not required prior to thrombolysis.

Principal Findings:

A total of 370 patients were enrolled (188 to antistreplase and 182 to streptokinase). The groups were well matched at baseline in terms of age, medical history including hypertension and diabetes, cardiac history, time to therapy, and infarct-related vessel. There were slightly more women in the antistreplase arm (27% vs. 18%, p=0.05). Time from onset of symptoms to treatment averaged 158 minutes for all patients. Eleven enrolled patients (3%) did not receive therapy due to intervention before 90 minutes, unsuccessful catheterization, hemodynamic instability, or administrative problems.

Rates of angioplasty or CABG during hospitalization were similar between the two arms. Angioplasty was performed in 49% of the antistreplase patients and 52% of the streptokinase patients. CABG was performed in 21% of the antistreplase patients and 21% of the streptokinase patients.

At early angiography (90-240 minutes), the patency rate (TIMI grade 2 or 3 flow) was similar between groups (72.1% for antistreplase vs. 73.3% for streptokinase, p=0.80). Among patients with patent arteries at initial angiography, rates of TIMI grade 3 perfusion were slightly higher in the antistreplase arm (83% vs. 72%, p=0.03). The antistreplase arm also showed slightly better residual stenosis in the infarct-related artery among patients with TIMI 2 or 3 flow (74% vs. 77.2%, p=0.02).

A total of 190 patients with initially patent arteries who did not undergo intervention were restudied angiographically at 24 hours. Only 1 of 96 antistreplase patients and 1 of 94 streptokinase patients had reoccluded. Among patients with continued patency, TIMI grade 3 flow was found in 93% of the antistreplase patients and 91% of the streptokinase patients.

Mortality was similar in both arms (5.9% antistreplase vs. 7.1% streptokinase, p=0.61). Occurrence rates of any bleeding problem were similar between groups (54% antistreplase vs. 57% streptokinase, p=0.65). There were no significant differences between arms in rates of stroke, heart failure, hypotension, or serious arrhythmias.

Interpretation:

Among patients with ST-segment elevation myocardial infarction, antistreplase was associated with similar rates of vessel patency, need for mechanical intervention, and adverse events compared with streptokinase. Antistreplase therapy was associated with a slightly lower residual percent stenosis in the infarct-related artery and slightly higher rates of TIMI 3 flow compared with streptokinase.

References:

Anderson JL, Sorensen SG, Moreno FL, et al. Multicenter patency trial of intravenous anistreplase compared with streptokinase in acute myocardial infarction. The TEAM-2 Study Investigators. Circulation 1991;83:126-40.

Clinical Topics: Cardiac Surgery, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Aortic Surgery, Cardiac Surgery and Heart Failure, Lipid Metabolism, Novel Agents, Acute Heart Failure, Interventions and Imaging, Angiography, Nuclear Imaging, Hypertension

Keywords: Myocardial Infarction, Stroke, Hypotension, Constriction, Pathologic, Fibrinolytic Agents, Angioplasty, Balloon, Coronary, Hemodynamics, Streptokinase, Coronary Angiography, Heart Failure, Catheterization, Anistreplase, Coronary Vessels, Coronary Artery Bypass, Hypertension, Diabetes Mellitus


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