Tissue plasminogen activator: Toronto (TPAT) placebo-controlled randomized trial in acute myocardial infarction

Abstract

The efficacy and safety of recombinant tissue plasminogen activator (rt-PA) administered on a dosing per weight basis was evaluated in a randomized, placebo-controlled, double-blind trial in 115 patients with acute myocardial infarction. The principal outcomes were global and regional left ventricular function in the distribution of the qualifying myocardial infarction, determined 9 days after the onset of symptoms. Global and regional ejection fraction values were significantly better for patients treated with rt-PA than for placebo-treated patients (the differences were 5.8 +/- 2.7% units [p = 0.017] and 7.1 +/- 3.1% units [p = 0.012], respectively). This benefit was also evident from visual assessment of left ventricular segmental wall motion. After adjustment for differences in important prognostic variables at baseline, the estimates of treatment effect were 4.0 +/- 2.4% units (p = 0.048) for global and 4.3 +/- 2.6% units (p = 0.047) for regional ejection fraction. Early patency of the infarct-related vessel was demonstrable in 7 (29%) of 24 placebo-treated patients and 18 (78%) of 23 rt-PA-treated patients, whereas 15 (56%) of 27 patients in the placebo group and 23 (72%) of 32 in the rt-PA group had a patent infarct-related vessel at hospital day 9. There was no significant difference in irreversible or reversible defect size as assessed by thallium scintigraphy on day 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Endothelial Fibrinolytic Capacity Predicts Future Adverse Cardiovascular Events in Patients With Coronary Heart Disease

“…The importance of endogenous t-PA release is exemplified by the high rate of spontaneous reperfusion in the infarct related artery after acute myocardial infarction, occurring in up to 30% of patients within the first 12 hours. [27][28][29] Any reduction in the acute dynamic fibrinolytic response decreases the capacity to lyse intraluminal thrombus and the likelihood of restoring vessel patency. In this prospective observational cohort study, we have further demonstrated that the capacity to release t-PA appears to be a major determinant of the risk of cardiovascular events and suggests that endothelial fibrinolytic capacity has a crucial role in the pathogenesis of atherothrombosis.…”

Tissue-type plasminogen activator improves neurological functions in a rat model of thromboembolic stroke.

“…The dosage is also similar to that used in reported clinical trials for the treatment of acute myocardial infarction. 28 - 29 The dose of urokinase in this study was chosen following the results of a rabbit model of jugular vein thrombosis 30 in which systemic infusion of urokinase resulted in significant thrombolysis at a dose 4.8 x 10…”

Stimulated Tissue Plasminogen Activator Release as a Marker of Endothelial Function in Humans

“…3 The importance of acute endogenous t-PA release is further exemplified by the high rate of spontaneous reperfusion in the infarct-related artery after acute myocardial infarction. 78 A reduction in t-PA activity or release is associated with an increased incidence of major adverse cardiac events in patients with stable 79 or unstable angina. 36 Rosenberg and Aird 3 have postulated that vascular bed-specific defects in hemostasis exist, and that coronary thrombosis critically depends on local fibrinolytic balance.…”