Assessment of the Safety and Efficacy of a New Thrombolytic: TNK-tPA - ASSENT-2

Description:

Single-dose TNK-tPA vs. accelerated tPA for mortality in acute MI.

Hypothesis:

To demonstrate therapeutic equivalence of TNK-tPA with accelerated tPA.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 16,950

Patient Populations:

Age > 18
Acute myocardial infarction pain beginning within 6 hours of enrollment
ST segment elevation or new left bundle branch block on ECG

Primary Endpoints:

All-cause mortality at 30 days

Secondary Endpoints:

Stroke, intracranial hemorrhage, bleeding complications, and net clinical effect

Drug/Procedures Used:

Weight-adjusted single doses of TNK-tPA (30mg for patients < 60kg; 35 mg for patients between 60 and 70 kg; up to 50mg for patients > 90kg) versus accelerated tPA.

Concomitant Medications:

All patients received concomitant treatment with aspirin and heparin (titrated to an aPTT of 50 to 75 seconds).

Principal Findings:

A total of 445 patients were not treated, 232 of whom received primary angioplasty instead.

Thirty-day mortality was 6.17% for the TNK-tPA group compared to 6.15% for the accelerated t-PA group, and was statistically equivalent. The survival curves on Kaplan-Meier analysis revealed near-complete overlap of the two groups during the 30-day follow-up period.

There were no significant differences in treatment groups seen on subgroup analysis except in those patients treated after 4 hours of the onset of chest pain. In this subgroup, the mortality rate was 7.04% in TNK-tPA versus 9.19% in t-PA (P < 0.05). This may be due to the increased fibrin specificity inherent in the TNK-tPA agent.

The incidences of stroke were similar in the two treatment groups, with 1.78% occurring in the TNK-tPA group versus 1.66% in the tPA group (P-value - 0.55). The combined endpoint of death or nonfatal stroke were similar (7.1% in TNK-tPA versus 7.04% in tPA, relative risk 1.01). Mild to moderate bleeding was seen less commonly in TNK-tPA-treated patients compared with tPA-treated subjects - 26% vs. 28.1% (P -value - 0.002).

Interpretation:

TNK-tPA is a mutant form of tPA that substitutes six amino acid bases from the wild-type agent. Limited safety and efficacy data have been previously described in the TIMI 10A and 10B trials, as well as the ASSENT-1 trial. The investigators conclude that single-bolus TNK-tPA is equivalent to tPA in terms of its 30-day mortality benefit. The risks of cerebral vascular events are similar; however, mild-to-moderate bleeding may be less likely to occur in TNK-tPA-treated patients.

References:

1. Presented at the ACC 48th Scientific Sessions, New Orleans, LA, 1999

Clinical Topics: Arrhythmias and Clinical EP, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, EP Basic Science, Lipid Metabolism

Keywords: Risk, Stroke, Kaplan-Meier Estimate, Myocardial Infarction, Follow-Up Studies, Fibrinolytic Agents, Electrocardiography, Angioplasty, Chest Pain, Bundle-Branch Block, Tissue Plasminogen Activator, Fibrin, Hemorrhage


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