Coronary recanalization rate after intravenous bolus of alteplase in acute myocardial infarction

The demonstration in animals that recombinant tissue-type plasminogen activater 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 5O, 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 S hours of onset of symptoms with an intravenous 70-mg bolus dose of alteplase (or 80 mg if body weight was >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 recanallzation rate of the infarct-related coronary artery was 55% (95% confidence interval, 43 to 66%) at 60 minutes and 480/o (950/o 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 +/- O.56, 1.59 +/- 0.85 and 1.64 +/- 0.84 g/liter, respectively, when assessed as total clottable protein, and 2.55 +/- 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% (950/o confidence interval, S3 to 750/o) of patients and occurred primarily at puncture sites. in 6 patients a transient decrease of systolic blood pressure (Am J Cardiol 1991;68:161-16S)
Acute myocardial infarction (AMI; heart attack) occurs when one or more of the coronary arteries supplying blood to the heart muscle become blocked, resulting in myocardial ischemia (diminution of blood flow to the heart). If not promptly reversed, this can cause death or permanent cardiac damage. One method for treating AMI is the administration of thrombolytic (clot-dissolving) drugs (such as streptokinase, urokinase, or tissue-type plasminogen activator), which enzymatically dissolve the blockage, restoring blood flow to the heart muscle (recanalization). Because tissue-type plasminogen activator (rt-PA) is rapidly cleared from the blood, treatment with this drug is usually given by prolonged infusion. Preliminary evidence suggests that the thrombolytic effect of rt-PA outlasts its presence in the blood, raising the possibility of using discrete (bolus) injections rather than infusions. To characterize the relative efficacy of infusion and bolus methods of administering rt-PA, 60 patients were given a bolus injection of rt-PA; those patients exhibiting recanalization were randomly assigned to receive an additional (lower) dose of rt-PA either as a bolus or as a prolonged infusion. The recanalization rate for patients given the initial bolus dose was 55 percent and 48 percent at 60 and 90 minutes, respectively. The patients receiving the additional dose of rt-PA showed similar low rates of repeated blocking (0 to 4 percent), regardless of whether the drug was given as a bolus or as an infusion. The overall success rate (measured by recanalization) using that pattern was lower than has been previously reported; hence, bolus injection of rt-PA is not the optimal mode of administration. (Consumer Summary produced by Reliance Medical Information, Inc.)