Randomized angiographic trial of recombinant tissue-type plasminogen activator (alteplase) in myocardial infarction

Abstract

Clot dissolution with restoration of infarct-related artery blood flow is the likely mechanism for the improved prognosis and mortality reduction seen after thrombolytic therapy of acute myocardial infarction. A pilot study has suggested that 100 mg of recombinant tissue-type plasminogen activator (rt-PA) infused over 90 min may lead to higher patency rates than the current standard of 100 mg over 3 h. In this multicenter, randomized, open label trial, 281 patients with acute myocardial infarction receive 100 mg of rt-PA according to either the standard 3-h infusion regimen (an initial 10-mg bolus followed by 50 mg for the 1st h, then 20 mg/h for 2 h) or an accelerated 90-min regimen (15-mg bolus followed by 50 mg over 30 min, then 35 mg over 60 min). All patients also received intravenous heparin and oral aspirin during and after rt-PA infusion. At 60 min after initiation of the rt-PA infusion, the observed angiographic patency rates were 76% (95% confidence intervals 65% to 84%) in the accelerated regimen group and 63% in the control group (52% to 73%, p = 0.03). At 90 min these rates were 81% (73% to 87%) and 77% (68% to 84%), respectively (p = 0.21). Both randomized groups experienced similar rates of recurrent ischemia, reinfarction, angiographic reocclusion, other complications of myocardial infarction (including stroke and death) and bleeding complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombolytic therapy for acute myocardial infarction

“…Higher dose and double-bolus regimens have been associated with unacceptable bleeding rates [8,9]. The accelerated or front-loaded dosing regimen has been shown to have higher early patency rates, similar safety profile [6], and lower incidences of reocclusion as compared with the standard dosing regimen [10]. The GUSTO I study (41,021 patients) tested the accelerated dose regimen combined with intravenous heparin.…”

“…Heparin and aspirin should be given concomitantly to prevent reocclusion. The accelerated dosing regimen has been proven to be the most effective [6]: 15 mg bolus over 1-2 min followed by 0.75 mg/kg IV (Յ 50mg) over 30 min followed by 0.5 mg/kg (Յ 35 mg) over 60 min. Weight adjustment is recommended because of excessive bleeding in lighter weight (Ͻ 60 kg) patients and a trend toward decreased lysis in heavy weight (Ͼ 90 kg) individuals [7].…”

A comparison of intra-arterial and intravenous tissue-type plasminogen activator on autologous arterial emboli in the cerebral circulation of rabbits.

“…In patients receiving intravenous thrombolytic therapy for acute myocardial infarction, angiography 90 minutes after the initiation of treatment has demonstrated that effective thrombolysis is achieved less frequently with streptokinase (43% to 64%) 24 36 Recently the use of accelerated intravenous dosing regimens of TPA has produced superior results, with 90-minute patency rates ranging from 82% to 91% (mean, 85%) in five studies of a combined total of more than 500 patients. 33 -3740 Thus, for TPA the thrombolytic efficacy of intra-arterial and intravenous routes may be nearly equal.…”

Interventions for ST Elevation Myocardial Infarction in Women

“…Despite the benefit and widespread application of fibrinolytic therapy in the treatment of STEMI, bleeding complications, including devastating hemorrhagic strokes, present a major limitation of this therapy, beyond the substantial proportion (approximately 20%-30%) of patients with failed reperfusion [108][109][110][111][112] and recurrent ischemia. 98,[113][114][115] Although thrombolytics can restore epicardial coronary artery flow, it does not address the underlying unstable plaque and the exposed thrombogenic material thought to cause recurrent ischemic events.…”