It is now established that the precipitating event in most transmural myocardial infarctions is coronary thrombosis. Experimental evidence in animals and experience in man have shown that thrombolysis in the early hours after the onset of infarction can interrupt and, in some cases, possibly prevent irreversible myocardial necrosis. Thrombolysis can be achieved in 70-80% of patients by the intracoronary administration of streptokinase. Although this treatment is effective in achieving clot lysis and coronary reperfusion, it is probably of major benefit only when applied in the first 1 to 3 hours after the onset of transmural ischemia. Experience in the first 100 patients randomized by ourselves in the western Washington Intracoronary streptokinase Trial has shown that it is extremely difficult to establish reperfusion in less than three hours. The average time to reperfusion in this trial has been more than six hours. Since the emergency coronary care systems in Seattle, King County, and many of the other communities in Western Washington are among the best in the world, it is unlikely that this time to treatment can be significantly shortened. Because of the constraint for most patients, we have concluded that effective, i.e., yearly, thrombolytic therapy will require an intravenous approach. The proposed Intravenous Streptokinase Randomized Trial will evaluate the effectiveness and practicality of this form of thrombolytic therapy in a community setting. The primary end-point of the trial is 14-day mortality. The secondary end-points include: 1) success of thrombolysis, as judged by angiographic patency of the involved coronary artery at 10-14 days; 2) early and late global left ventricular function by serial radionuclide angiography; 3) segmental wall motion analysis as judged by tomographic blood pool imaging at late (30-45 days) follow-up; and 4) myocardial infarction size as measured by quantitative Thallium-201 emission computer tomography (at 30-45 days). Six hundred patients will be enrolled over 3 years. A reduction in mortality from 14 to 7% will be detected with 90% certainty at the p less than .05 level. Reductions in global or regional ejection fraction of 5 EF points, as well as infarct size reduction of 50%, will be similarly detectable. Additionally, 6-month follow-up will assess mortality, reinfarction and coronary bypass surgery rates to document whether any initially reduced mortality/morbidity is sustained.
| Cerqueira, M D; Maynard, C; Ritchie, J L et al. (1992) Long-term survival in 618 patients from the Western Washington Streptokinase in Myocardial Infarction trials. J Am Coll Cardiol 20:1452-9 |
| Cerqueira, M D; Maynard, C; Ritchie, J L (1991) Radionuclide assessment of infarct size and left ventricular function in clinical trials of thrombolysis. Circulation 84:I100-8 |
| Martin, G V; Sheehan, F H; Stadius, M et al. (1988) Intravenous streptokinase for acute myocardial infarction. Effects on global and regional systolic function. Circulation 78:258-66 |
| Kennedy, J W; Martin, G V; Davis, K B et al. (1988) The Western Washington Intravenous Streptokinase in Acute Myocardial Infarction Randomized Trial. Circulation 77:345-52 |
| Ritchie, J L; Cerqueira, M; Maynard, C et al. (1988) Ventricular function and infarct size: the Western Washington Intravenous Streptokinase in Myocardial Infarction Trial. J Am Coll Cardiol 11:689-97 |
