INDICATIONS FOR FIBRINOLYTIC THERAPY IN SUSPECTED ACUTE MYOCARDIAL-INFARCTION - COLLABORATIVE OVERVIEW OF EARLY MORTALITY AND MAJOR MORBIDITY RESULTS FROM ALL RANDOMIZED TRIALS OF MORE THAN 1000 PATIENTS

Large randomised trials have demonstrated that fibrinolytic therapy ca n reduce mortality in patients with suspected acute myocardial infarct ion (AMI). The indications for, and contraindications to, this treatme nt in some categories of patient are disputed, examples being late pre sentation, elderly patients, and those in cardiogenic shock. This over view aims to help resolve some of the remaining uncertainties. From al l trials of fibrinolytic therapy versus control that randomised more t han 1000 patients with suspected AMI, information was sought and check ed on deaths during the first 5 weeks and on major adverse events occu rring during hospitalisation. The nine trials included 58 600 patients , among whom 6177 (10.5%) deaths, 564 (1.0%) strokes, and 436 (0.7%) m ajor non-cerebral bleeds were reported. Fibrinolytic therapy was assoc iated with an excess of deaths during days 0-1 (especially among patie nts presenting more than 1.2 h after symptom onset, and in the elderly ) but this was outweighed by a much larger benefit during days 2-35. T his ''early hazard'' should not obscure the very clear overall surviva l advantage that is produced by fibrinolytic therapy. Benefit was obse rved among patients presenting with ST elevation or bundle-branch bloc k (BBB)-irrespective of age, sex, blood pressure, heart rate, or previ ous history of myocardial infarction or diabetes and was greater the e arlier treatment began. Among the 45 000 patients presenting with ST e levation or BBB the relation between benefit and delay from symptom on set indicated highly significant absolute mortality reductions of abou t 30 per 1000 for those presenting within 0-6 h and of about 20 per 16 00 for those presenting 7-12 h from onset, and a statistically uncerta in benefit of about 10 per 1000 for those presenting at 13-18 h (with more randomised evidence needed in this latter group to assess reliabl y the net effects of treatment). Fibrinolytic therapy was associated w ith about 4 extra strokes per 1000 during days 0-1: of these, 2 were a ssociated with early death and so were already accounted for in the ov erall mortality reduction, 1 was moderately or severely disabling, and 1 was not. This overview indicates that fibrinolytic therapy is benef icial in a much wider range of patients than is currently given such t reatment routinely.