GUSTO confirms speed advantage
Reteplase is faster, but otherwise similar
Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) investigators concluded recently that, as compared with alteplase (plasminogen activator), reteplase (recombinant plasminogen activator) was easier to administer and allowed reperfusion of more patients. The safety and efficacy of both substances were confirmed in the large GUSTO III trial.1"The drug had a 30-minute advantage," says Richard W. Smalling, MD, PhD, co-director of cardiology at The University of Texas-Houston Medical School and a principal in the GUSTO III trial. "It opened arteries more effectively and in more patients after 60 minutes than alteplase did in 90." Beyond that, however, reteplase exhibited no additional survival benefit and resulted in similar outcomes. A mutant of alteplase, reteplase has a longer half-life and is a nonglycosylated recombinant plasminogen activator that converts plasminogen to plasmin, an enzyme that helps break down the blood clots that block arteries.
A question that remains is whether a quickly administered lytic actually improve the process of acute myocardial infarction (AMI) management.
More than 15,000 patients from 800 hospitals in 20 countries participated in the clinical trial. Each presented within six hours of symptom onset with ST-segment elevation or bundle-branch block. They were randomly assigned to receive either reteplase in two bolus doses of 10.8 U (18.8 mg) each given 30 minutes apart or an accelerated infusion of alteplase, up to 100 mg (weight adjusted), given as a 15 mg initial bolus followed by IV infusion over 90 minutes.
A goal now is to reduce patient response time during a heart attack. According to Eric J. Topol, MD, chairman of the GUSTO study and chairman of the department of cardiology at The Cleveland Clinic, AMI deaths could be reduced by 15% if time between symptom onset and commencement of treatment were reduced to under an hour. Today that net time is on average 2.3 hours. Of the 1.25 million Americans who experience a heart attack annually, half a million die, and half of those die within the first hour of their symptoms before reaching a hospital.
Would a double-bolus of alteplase work as well as continuous infusion? The COBALT investigators tested that hypothesis.2 Thirty-day mortality was higher in the double-bolus group than in the accelerated-infusion group, and there was a higher rate of intracranial hemorrhage as well.
References
1. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO III) Investigators. A comparison of reteplase with alteplase for acute myocardial infarction. N Engl J Med 1997; 337:1,118-1,123.
2. The Continuous Infusion versus Double-Bolus Administration of Alteplase (COBALT) Investigators. A comparison of continuous infusion of alteplase with double-bolus administration for acute myocardial infarction. N Engl J Med 1997; 337:1,124-1,130.
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