TNKase - Assessment of the Safety and Efficacy of New Thrombolytic (ASSENT - 2)

International, multicenter, randomized, double-blind, phase III trial

ASSENT-2: Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) Investigators. Single bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomized trial. Lancet. 1999;354:716-722.

Objective
Double-blind, randomized, controlled Phase III trial to compare the efficacy and safety of accelerated infusion of Activase and single bolus TNKase dosed according to estimated or actual weight if available.

Primary Endpoint and Results
All-cause mortality at 30 days
>	6.2% for TNKase (N=8461), 6.2% for Activase (N=8488) (relative risk 1.00; 95% CI = 0.89–1.12)
Secondary Endpoints and Results
Intracranial hemorrhage (ICH) at 30 days
>	0.9% for TNKase (N=8461), 0.9% for Activase (N=8488) (relative risk 0.99; 95% CI = 0.73–1.35)
Any stroke at 30 days
>	1.8% for TNKase, 1.7% for Activase (relative risk 1.07; 95% CI = 0.86–1.35)
Death or non-fatal stroke at 30 days
>	7.1% for TNKase, 7.0% for Activase (relative risk 1.01; 95% CI = 0.91–1.13)
Major non-cerebral bleeding events
>	Reduced rate of major non-cerebral bleeding*—4.7% for TNKase, 5.9% for Activase (p=0.0002, relative risk 0.78; 95% CI = 0.69–0.89)
>	Trend toward reduced rate of minor non-cerebral bleeding—21.8% for TNKase, 23.0% for Activase (p=0.0553; relative risk 0.94; 95% CI = 0.89–1.00)
>	Reduced need for blood transfusions—4.3% for TNKase, 5.5% for Activase (p=0.0002; relative risk 0.77; 95% CI = 0.67–0.89)

Indication:
For use in mortality reduction associated with acute myocardial infarction (AMI). Treatment should be initiated as soon as possible after the onset of AMI symptoms.

Important Safety Information:
TNKase therapy in patients with acute myocardial infarction is contraindicated in the following certain situations (eg, active internal bleeding, history of cerebrovascular accident, known bleeding diathesis, severe uncontrolled hypertension) because of an increased risk of bleeding [See CONTRAINDICATIONS in full prescribing information].

The most common complication encountered during TNKase therapy is bleeding. Should serious bleeding (not controlled by local pressure) occur, any concomitant heparin or antiplatelet agents should be discontinued immediately.

In certain conditions (eg, recent major surgery, cerebrovascular disease, hypertension) the risk of TNKase therapy may be increased and should be weighed against the anticipated benefits. [See WARNINGS in full prescribing information].

Cholesterol embolism has been reported rarely in patients treated with all types of thrombolytic agents; the true incidence is unknown.

Coronary thrombolysis may result in arrhythmias associated with reperfusion. It is recommended that anti-arrhythmic therapy for bradycardia and/or ventricular irritability be available when TNKase is administered.

Please see full prescribing information for additional important safety information.