Alteplase, safety

Reperfusion of Stroke Safety Study Imaging Evaluation-2 Adjunctive Treatment to Standard Alteplase Therapy of Ischemic Stroke. Presented at the 29th International Stroke Conference Fehmary 2004. 

F. Role in therapy Reteplase is a novel thrombolytic agent. It has a longer half-life than alteplase, which allows bolus administration. Its administration technique is much simpler than that of alteplase. In addition reteplase has achieved more rapid, complete, and sustained thrombolysis of the infarct-related artery compared to standard doses of alteplase with comparable safety. Reteplase is at least as effective as streptokinase and alteplase in AMI. 

Alteplase was the first commercially available recombinant tissue-type plasminogen activator (rt-PA) (25), It has a plasma half-life of less than five minutes and is metabolized by the liver, This agent was initially hailed as fibrin-specific unlike its precursors (urokinase and streptokinase). It was thought that this would result in a better safety profile, but this has not been born out in either the coronary or the peripheral experience, where actually there may be a higher bleeding risk as infusion time increases. Alteplase is currently indicated for use in the treatment of myocardial infarction, acute ischemic stroke, and pulmonary embolism. 

Early experience with this lytic in the treatment of peripheral arterial disease has been promising with equivalent safety and efficacy to alteplase (3 1,32). Burkart et al. published their initial experience in 13 patients with arterial occlusion and five with venous thrombosis. TNK-tPAwas administered at a rate of 0,25 mg/hr with restoration of flow in all patients, The clinical success with respect to limb salvage or symptom relief was achieved in I I of 13 (85%) patients and four out of the five patients with venous thrombosis, There were no intracranial bleeding complications,... 

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 1000 354 716-722. 

Other Phase IV studies and studies based on routine clinical practice The standard treatment with Alteplase to reverse stroke stndy (STARS) [55] inclnded 389 patients treated within 3 h of stroke onset. The Canadian Activase for Stroke Effectiveness Stndy (CASES) [56] inclnded 1,132 patients from 60 centers in Canada. These two Phase IV stndies demonstrated ontcomes and safety comparable to the NINDS trials. 

From 1995 through 2002, we participated in four international randomized studies and one collaborative study with the University of Vermont in which pharmacological thrombolysis was employed with alteplase [tissue-type plasminogen activator (t-PA)] or tenecteplase [TNK-t-PA (TNK)]. In this chapter we summarize our experience with the cohorts of patients in all of these studies who were studied in the United Arab Emirates (UAE). The first of the studies was the Continuous Infusion versus Double Bolus of Alteplase (COBALT) study. The other three were Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT I, II, III) studies and a substudy in ASSENT II with the University of Vermont (4-8). The last study, a collaborative one with the University of Vermont, was the Enhanced Rapidity of RECanah-zation with Tenecteplase compared with Alteplase (ERRECTA) study, results of which have not yet been published. All of the patients participating in ERRECTA were patients in the UAE. 

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