Fibrinolytic Therapy Trialists' Collaborative Group - FTT

Description:

This was a meta-analysis of all randomized, thrombolytic trials for suspected acute myocardial infarction enrolling 1000 or more patients. The meta-analysis sought to determine the indications and contraindications for fibrinolytic therapy.

Hypothesis:

Mortality would be reduced in patients treated with fibrinolytic therapy compared with controls for acute MI. A treatment benefit would be seen overall and in various patient subgroups.

Study Design

Study Design:

Patients Enrolled: 58600
Mean Follow Up: 35 days
Mean Patient Age: not reported
Female: 24

Patient Populations:

Randomized trials enrolling 1,000 or more patients in which fibrinolytic therapy has been compared with a control in patients with acute myocardial infarction. Unconfounded trials only, where one group differed from another only in the thrombolytic treatment.

Primary Endpoints:

0-35 day mortality

Secondary Endpoints:

0-35 day stroke mortality and stroke subgroup analysis: ECG findings, time to treatment, age, gender, SBP, heart rate, prior MI, diabetes

Drug/Procedures Used:

All trials randomized patients to fibrinoltyic therapy or control. Treatment for each trial was as follows: GISSI-1: streptokinase (SK), 1.5 MU vs open control ISAM: SK, 1.5 MU vs placebo; single IV bolus aspirin; IV heparin, 5000 U + 800-1000 U/h for 72-96 h AIMS: APSAC, 30 U vs placebo; IV heparin at 6 h, 1000-1500 U/h ISIS-2: SK, 1.5 MU vs placebo; aspirin ASSET: tPA, 100 mg vs placebo; IV heparin, 5000 U + 1000 U/h for 24 h USIM: urokinase, 1 MU x 2 bolus vs open control; IV heparin, 10000 U + 1000 U/h for 48 h ISIS-3: SK, 1.5 MU or tPA, 0.6 MU/kg or APSAC, 30 U vs open control; aspirin; SC heparin, 12500 U bd for 7 days EMERAS: SK, 1.5 MU vs placebo; aspirin LATE: tPA, 100 mg vs placebo; aspirin; IV heparin, 5000 U + 1000 U/h for 48 h

Principal Findings:

There was a 18% relative reduction in mortality to 35 days in fibrinolytic treated patients compared with controls (9.6% vs 11.5%, p<0.00001); however, the benefit was not seen until after day 1. Mortality was significantly reduced among patients presenting with ST segment elevation (21%, p<0.00001) or LBBB (25%, p<0.01); however, no differences were seen in patients presenting without ST elevation or LBBB. Both proportional and absolute mortality reductions were greater in patients treated earlier after symptom onset. Significant treatment benefit was seen up to 12 hours, but not in patients presenting >12 hours after symtom onset. Subgroup analysis showed a mortality reduction with thrombolytic therapy in all age groups except those >=75 years; both men and women; among patients with or without prior MI; and among diabetic and non-diabetic patients. Fibrinolytic therapy was associated with a small but significant increase in strokes (1.2% vs 0.8%, p<0.00001), with all of the excess occurring on day 0/1 and due to an increase in cerebral hemorrhage.

Interpretation:

This meta-analysis shows that fibrinolytic therapy for acute MI is beneficial in reducing mortality, despite a small increase in stroke. This treatment effect is beneficial among varying types of patients, but not for those without ST elevation or LBBB.

References:

Lancet 1994 Feb 5;343(8893):311-22

Clinical Topics: Anticoagulation Management, Dyslipidemia, Lipid Metabolism, Novel Agents

Keywords: Thrombolytic Therapy, Myocardial Infarction, Stroke, Urokinase-Type Plasminogen Activator, Streptokinase, Heparin, Anistreplase, Tissue Plasminogen Activator, Diabetes Mellitus, Cerebral Hemorrhage


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