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

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 received 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 alter 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. Fifteen percent of the patients who had a patent artery at 60 min had recurrent ischemia compared with 33% of those who had an occluded artery at 60 min and a patent artery at 90 min.These data indicate that an accelerated 100-mg dose of rt-PA. can produce more rapid reperfusion rates without an apparent change in the safety profile from the standard regimen. Subset analysis suggests that different serial angiographic profiles may predict different prognoses. Larger trials will determine whether increasing the frequency and speed of reperfusion will lead to improved prognosis after myocardial infarction.