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Intravenous tissue plasminogen activator and size of infarct, left ventricular function, and survival in acute
1Division of Cardiology, University Hospital, Gasthuisberg, Leuven, Belgium.
Insights
Recombinant tissue plasminogen activator significantly reduced mortality and infarct size in acute myocardial infarction patients. Early treatment improved left ventricular function and survival, despite an increased risk of bleeding complications.
Area of Science:
- Cardiology
- Pharmacology
- Biomedical Science
Background:
- Acute myocardial infarction (AMI) poses a significant threat to cardiac function and survival.
- Timely intervention is crucial to limit infarct size and preserve left ventricular function.
- Recombinant tissue type plasminogen activator (rt-PA) is a thrombolytic agent with potential benefits in AMI.
Purpose of the Study:
- To evaluate the efficacy of intravenous rt-PA in reducing infarct size.
- To assess the impact of rt-PA on left ventricular function post-AMI.
- To determine the effect of rt-PA on survival rates in patients with acute myocardial infarction.
Main Methods:
- A double-blind, randomized, placebo-controlled trial involving 721 patients with AMI within five hours of symptom onset.
- Patients received either intravenous rt-PA (100 mg over 3 hours) or placebo, alongside aspirin and heparin.
- Left ventricular function, enzymatic infarct size, clinical course, and three-month survival were assessed.
Main Results:
- Mortality was reduced by 51% at 14 days and 36% at three months in the rt-PA group.
- Treatment within three hours showed an 82% reduction in 14-day mortality.
- rt-PA reduced enzymatic infarct size by 20%, improved left ventricular ejection fraction by 2.2%, and decreased cardiac complications, but increased bleeding risk.
Conclusions:
- Intravenous rt-PA, combined with heparin and aspirin, effectively reduces infarct size and preserves left ventricular function in AMI.
- This treatment strategy significantly decreases mortality and cardiac complications.
- An increased risk of bleeding complications is associated with rt-PA therapy, necessitating careful patient selection and monitoring.
Study Objective:
To assess effect of intravenous recombinant tissue type plasminogen activator on size of infarct, left ventricular function, and survival in acute myocardial infarction.
Design:
Double blind, randomised, placebo controlled prospective trial of patients with acute myocardial infarction within five hours after onset of symptoms.
Setting:
Twenty six referral centres participating in European cooperative study for recombinant tissue type plasminogen activator.
Patients:
Treatment group of 355 patients with acute myocardial infarction allocated to receive intravenous recombinant plasminogen activator. Controls comprised 366 similar patients allocated to receive placebo.
Intervention:
All patients were given aspirin 250 mg and bolus injection of 5000 IU heparin immediately before start of trial. Patients in treatment group were given 100 mg recombinant tissue plasminogen activator over three hours (10 mg intravenous bolus, 50 mg during one hour, and 40 mg during next two hours) by infusion. Controls were given placebo by same method. Full anticoagulation treatment and aspirin were given to both groups until angiography (10-22 days after admission). beta Blockers were given at discharge.
End Point:
Left ventricular function at 10-22 days, enzymatic infarct size, clinical course, and survival to three month follow up.
Measurements And Main Results:
Mortality was reduced by 51% (95% confidence interval -76 to 1) in treated patients at 14 days after start of treatment and by 36% (-63 to 13) at three months. For treatment within three hours after myocardial infarction mortality was reduced by 82% (-95 to -31) at 14 days and by 59% (-83 to -2) at three months. During 14 days in hospital incidence of cardiac complications was lower in treated patients than controls (cardiogenic shock, 2.5% v 6.0%; ventricular fibrillation, 3.4% v 6.3%; and pericarditis, 6.2% v 11.0% respectively), but that of angioplasty or artery bypass, or both was higher (15.8% v 9.6%) during the first three months. Bleeding complications were commoner in treated than untreated patients. Most were minor, but 1.4% of treated patients had intracranial haemorrhage within three days after start of infusion. Enzymatic size of infarct, determined by alpha hydroxybutyrate dehydrogenase concentrations, was less (20%, 2p = 0.0018) in treated patients than in controls. Left ventricular ejection fraction was 2.2% higher (0.3 to 4.0) and end diastolic and end systolic volumes smaller by 6.0 ml (-0.2 to -11.9) and 5.8 ml (-0.9 to -10.6), respectively, in treated patients.
Conclusion:
Recombinant tissue type plasminogen activator with heparin and aspirin reduces size of infarct, preserves left ventricular function, and reduces complications and death from cardiac causes but at increased risk of bleeding complications4+