Intravenous and intracoronary fibrinolytic therapy in acute myocardial infarction: Overview of results on mortality, reinfarction and side-effects from 33 randomized controlled trials

During the past 25 years, 24 randomized trials of intravenous(IV) fibrinolytic treatment have been reported, involving atotal of some 6000 patients in the acute phase of myocardialinfarction. Most tested IV streptokinase (SK), but a few testedIV urokinase (UK). In the past 2 or 3 years numerous small randomizedtrials of intracoronary (IC) SK have been started, 9 of which,involving a total of about 1000 such patients have been reported.Because all of these IV and IC trials were small (the largestincluding only 747 patients), their separate results appearcontradictory and unreliable. But, an overview of the data fromthese trials indicates that IV treatment produces a highly significant(22%±5%, (P<0.001) reduction in the odds of death,an even larger reduction in the odds of reinfarction, and anabsolute frequency of serious adverse effects to set againstthis that is much smaller than the absolute mortality reduction.The apparent size of the mortality reduction in the IV trialswas similar whether anticoagulants were compulsory or optional,whether treatment was in a coronary cure unit or an ordinaryward and, surprisingly, whether treatment began early ( <6h from onset of symptoms) or late (generally 12–24 h).In addition, there was no evidence that UK was more effectivethan the less expensive SK, or that, despite their technicalcomplexity, the new IC regimes were more effective than theold IV regimes. Even the IV schedules that have been studied in randomized trialswere, however, quite complex, and the IC schedules were farmore so. Perhaps partly because of this, none of them is widelyused. If so, then some much simpler, and hence more widely practicable,IV SK regimes should be developed and tested. For example, asimple one hour high-dose IV SK infusion, without anticoagulation,will successfully convert virtually all of the available plasminogeninto plasmin. But, it may be several years before the net effectson mortality of any more widely practicable IV SK regimes canbe agreed unless many of the hospitals that do not wish routinelyto use IC regimes or the complex previous IV regimes will collaboratein multicentre randomized trials that can, if necessary, continuerapid intake until some tens of thousands of patients have beenrandomized, and some thousands of deaths have been observedamong the control and treated patients. The same, of course,may be true for any other fibrinolytic regimes (e.g. infusionof tissue plasminogen activator) if their net effects on mortalityare comparable to those of IV SK.