An approach to evaluating thrombolytic therapy in acute myocardial infarction. The 'unsatisfactory outcome' end point.

T he primary goal of thrombolytic therapy in acute myocardial infarction (AMI) is the early restoration of perfusion and maintenance of viability and function of myocardium that would otherwise undergo necrosis consequent to thrombotic coronary artery occlusion. The salvage achieved by thrombolysis ranges from a minute amount of myocardium of little functional significance to a large mass of heart muscle the necrosis of which could cause death, with an intermediate quantity in most patients. The most dramatic outcome of thrombolytic therapy is reduced in-hospital mortality,'-4 but early mortality is a relatively crude end point for measuring variations in the extent to which a given regimen accomplishes the primary goal of thrombolytic therapy defined above. Successful thrombolytic therapy also reduces the frequency of serious complications of AMI such as congestive heart failure and cardiogenic shock.5 Laboratory measurements reflecting benefit include preservation of left ventricular function and the early reestablishment and subsequent maintenance of patency of the infarct-related coronary artery. The favorable outcome of thrombolytic therapy is in some instances offset by recurrent infarction and by adverse effects, e.g., severe bleeding, including the most serious of all complications hemorrhagic stroke. These other (nonfatal) outcomes should also be taken into account in assessing thrombolytic therapy. The favorable effects of thrombolytic therapy have been clearly demonstrated in placebo-controlled trials, and when laboratory measurements such as coronary artery patency or left ventricular function are taken as end points, benefit can be shown in studies comprising only several dozen or a few hundred patients.5-10 To compare the effects of thrombolytic therapy and placebo on survival, however, trials involving several thousands of patients for each are required.1-4 With the exception of special groups of patients, such as those with ST segment depression and those who present relatively late, i.e., more than 6 hours after the onset of symptoms, the benefits of thrombolytic therapy on survival have now been so clearly established that placebocontrolled trials are no longer needed, nor would they