The exact relationship between coronary artery patency and clinical activity has not been established.

The safety and efficacy of the accelerated infusion of Alteplase have not been evaluated using antithrombotic or antiplatelet regimens other than those used in the GUSTO trial.

3-Hour Infusion in AMI Patients

In patients studied in a controlled trial with coronary angiography at 90 and 120 minutes following infusion of Activase, infarct artery patency was observed in 71% and 85% of patients (n=85), respectively.² In a second study, where patients received coronary angiography prior to and following infusion of Activase within 6 hours of the onset of symptoms, reperfusion of the obstructed vessel occurred within 90 minutes after the commencement of therapy in 71% of 83 patients.¹

The exact relationship between coronary artery patency and clinical activity has not been established.

In a double-blind, randomized trial (138 patients) comparing Activase to placebo, patients infused with Activase within 4 hours of onset of symptoms experienced improved left ventricular function at Day 10 compared to the placebo group, when ejection fraction was measured by gated blood pool scan (53.2% vs 46.4%, p=0.018). Relative to baseline (Day 1) values, the net changes in ejection fraction were +3.6% and -4.7% for the treated and placebo groups, respectively (p=0.0001). Also documented was a reduced incidence of clinical congestive heart failure in the treated group (14%) compared to the placebo group (33%) (p=0.009).⁷

In a double blind, randomized trial (145 patients) comparing Activase to placebo, patients infused with Activase within 2.5 hours of onset of symptoms experienced improved left ventricular function at a mean of 21 days compared to the placebo group, when ejection fraction was measured by gated blood pool scan (52% vs 48%, p=0.08) and by contrast ventriculogram (61% vs 54%, p=0.006). Although the contribution of Activase alone is unclear, the incidence of nonischemic cardiac complications when taken as a group (i.e., congestive heart failure, pericarditis, atrial fibrillation, and conduction disturbance) was reduced when compared to those patients treated with placebo (p < 0.01).⁸

In a double-blind, randomized trial (5013 patients) comparing Activase to placebo (ASSET study), patients infused with Activase within 5 hours of the onset of symptoms of acute myocardial infarction experienced improved 30-day survival compared to those treated with placebo. At 1 month, the overall mortality rates were 7.2% for the Activase treated group and 9.8% for the placebo treated group (p=0.001).^9,10 This benefit was maintained at 6 months for Activase-treated patients (10.4%) compared to those treated with placebo (13.1%, p=0.008).¹⁰ In a double-blind, randomized trial (721 patients) comparing Activase to placebo, patients infused with Activase within 5 hours of the onset of symptoms experienced improved ventricular function 10-22 days after treatment compared to the placebo group, when global ejection fraction was measured by contrast ventriculography (50.7% vs 48.5%, p=0.01). Patients treated with Activase had a 19% reduction in infarct size, as measured by cumulative release of HBD (c-hydroxybutyrate dehydrogenase) activity compared to placebo treated patients (p=0.001). Patients treated with Activase had significantly fewer episodes of cardiogenic shock (p=0.02), ventricular fibrillation (p < 0.04) and pericarditis (p=0.01) compared to patients treated with placebo. Mortality at 21 days in Activase treated patients was reduced to 3.7% compared to 6.3% in placebo treated patients (1-sided p=0.05).¹¹ Although these data do not demonstrate unequivocally a significant reduction in mortality for this study, they do indicate a trend that is supported by the results of the ASSET study.

Acute Ischemic Stroke Patients

Two placebo-controlled, double-blind trials (The NINDS t-PA Stroke Trial, Part 1 and Part 2) have been conducted in patients with acute ischemic stroke.¹² Both studies enrolled patients with measurable neurological deficit who could complete screening and begin study treatment within 3 hours from symptom onset. A cranial computerized tomography (CT) scan was performed prior to treatment to rule out the presence of intracranial hemorrhage (ICH). Patients were also excluded for the presence of conditions related to risks of bleeding (see CONTRAINDICATIONS), for minor neurological deficit, for rapidly improving symptoms prior to initiating study treatment, or for blood glucose of < 50 mg/dL or > 400 mg/dL.

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