CORONARY RECANALIZATION RATE AFTER INTRAVENOUS BOLUS OF ALTEPLASE IN ACUTE MYOCARDIAL-INFARCTION

The demonstration in animals that recombinant tissue-type plasminogen activator produces prolonged thrombolysis after its clearance from the circulation has prompted a few pilot studies of bolus administration in patients. Alteplase (bolus dose of 70 mg) resulted in the highest recanalization rate in our previous pilot study comparing bolus doses of 50, 60 and 70 mg of alteplase in patients with acute myocardial infarction. The aim of the present trial was to assess the efficacy and safety of the same bolus dose in a larger number of patients. A further objective was to study the angiographic reocclusion rate at 12 to 24 hours in patients who had a recanalized infarct-related coronary artery at 90 minutes and were randomized at that time to a bolus dose or an infusion for 3 hours of 30 mg of alteplase. Sixty patients with acute myocardial infarction and angiographically documented total occlusion of the infarct-related coronary artery before thrombolysis were treated within 5 hours of onset of symptoms with an intravenous 70-mg bolus dose of alteplase (or 80 mg if body weight was greater-than-or-equal-to 90 kg). Each patient received 5,000 IU of heparin intraarterially and 100 mg of aspirin by mouth before administration of alteplase. Coronary angiography was repeated 60 and 90 minutes after alteplase administration. The recanalization rate of the infarct-related coronary artery was 55% (95% confidence interval, 43 to 66%) at 60 minutes and 48% (95% confidence interval, 37 to 60%) at 90 minutes. Pretreatment levels of lipoprotein (a) were not significantly related to recanalization. Twenty-three patients, who had a patent infarct-related coronary artery during 90-minute angiography and did not require immediate coronary intervention, were then given an additional 30 mg of alteplase, randomly either as an intravenous bolus dose or as an intravenous infusion over 3 hours. Heparin treatment was continued in randomized patients with an intravenous infusion of 1,000 IU of heparin per hour between the time of the 90-minute angiography and the control angiography at 12 to 24 hours. At this final angiography, reocclusion of the infarct-related coronary artery was seen in 1 patient randomized to alteplase infusion (reocclusion rate 4%). Plasma fibrinogen (mean +/- standard deviation) before and 90 and 270 minutes after a bolus dose of alteplase was 2.74 +/- 0.56, 1.59 +/- 0.85 and 1.64 +/- 0.84 g/liter, respectively, when assessed as total clottable protein, and 2.85 +/- 1.04, 0.77 +/- 0.73 and 1.01 +/- 1.06 g/liter, respectively, when measured by a clotting rate assay. Only minor bleeding was observed in 65% (95% confidence interval, 53 to 75%) of patients and occurred primarily at puncture sites. In 6 patients a transient decrease of systolic blood pressure less-than-or-equal-to 90 mm Hg was observed during the first 90 minutes. There were no deaths within 14 days. In considering the recanalization rates obtained in this study, a 70-mg bolus injection of alteplase does not appear to be an optimally effective dosage regimen in the treatment of acute myocardial infarction.