Intravenous tissue plasminogen activator and size of infarct, left ventricular function, and survival in acute myocardial infarction.

Abstract

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). P3 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 ca 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 complications.

Temporal Trends in Cardiogenic Shock Complicating Acute Myocardial Infarction

“…14,15,28,29 Uncontrolled studies of bypass grafting show that this therapy improves short-term survival among patients with cardiogenic shock when they are treated soon after shock has developed. 30,31 Although thrombolytic therapy has consistently been shown to decrease mortality after acute myocardial infarction, 32,33 no large, randomized, controlled trial has found that the use of clot-lysing therapy reduces the incidence of cardiogenic shock or improves survival after cardiogenic shock has developed. In GUSTO-1, 56 percent of all patients with cardiogenic shock died in the hospital, regardless of the thrombolytic regimen used.…”

Intracranial Hemorrhage Associated With Thrombolytic Therapy for Elderly Patients With Acute Myocardial Infarction

“…The CCP database is rich in clinical information, and our cohort contains the biggest group of patients Ն75 years of age reported to date. Among the clinical trials, there were often exclusions for those beyond age 70 27,28 or 75 years. 29 -33 Blacks have higher rates of both ischemic and hemorrhagic stroke compared with whites.…”

Randomized comparison of rescue angioplasty with conservative management of patients with early failure of thrombolysis for acute anterior myocardial infarction.

“…Use of intra-aortic balloon counterpulsation was left to the discretion of the operator. After initial randomized treatment, all patients received aspirin (80 to 325 mg/d), intravenous nitrates for at least 24 vors. Sensitivity analyses were also performed using no imputation and imputation of 0% for nonsurvivors.…”