THERAPY AND PREVENTION THROMBOLYSIS A randomized trial of intravenous and intracoronary streptokinase in patients with acute myocardial infarction

The clinical effects of intravenous streptokinase in patients with acute myocardial infarction were compared with those of intracoronary streptokinase in a randomized, prospective study. Comparisons were also made with a historical control group. Fifty patients were entered into the study at 2.4 + 1.2 hr after onset of pain, and 27 were assigned to intravenous and 23 to intracoronary therapy. The doses of streptokinase averaged 212,000 U ic and 845,000 U iv (0.75 x 106 U/5 hr, n = 14 or 106 U/1 hr, n = 13). Results of studies of the two intravenous dosage schedules were similar and so were combined. Streptokinase was administered at 2.8 + 1.0 hr after onset of pain in the intravenous and at 4.3 + 1.4 hr in the intracoronary drug group (p < .001). Convalescent (day 10) radionuclide ejection fractions were 54 + 14% for the intravenous and 50 + 16% for the intracoronary drug group. Change in ejection fraction from day 1 to 10 tended to be greater after intravenous drug: 5.1% (p < .08) vs 1.2% (NS). Semiquantitative regional wall motion indexes in the infarct zone showed significant and similar modest improvement from admission to day 10 in both groups (p < .02). Accelerated enzyme-release kinetics were noted after both therapies. Times of peak enzyme levels for patients on intravenous and intracoronary drug were, respectively, 12.5 ± 5.0 and 11.5 + 4.3 hr for creatine kinase MB isoenzyme and 31.7 + 11.8 and 28.1 + 12.7 hr for lactic dehydrogenase (LDH). Peak LDH1 level was lower in patients receiving intravenous drug than in the historical control group (p < .05). Electrocardiographically summed ST segments diminished rapidly after therapy in both groups; Q wave development was similar and overall R wave loss was equivalent and less extensive compared with in historical control subjects. Infarct pain requiring morphine was diminished similarly in both treatment groups. Incidence of early arrhythmias and heart failure also did not differ. Posttherapy ischemic events and early surgery tended to be more common in the intracoronary group and bleeding was more common in the intravenous group. Intravenous drug did not decrease early hospital mortality (intravenous drug 5, historical control = 4, intracoronary drug 1); the differences in this parameter among groups were not significant. At convalescent angiographic evaluation, anterograde perfusion was present in 73% of those receiving intravenous and 76% of those receiving intracoronary drug. Thus, favorable relative effects were noted on cardiac function, clinical evaluations, and hospital course after intravenous streptokinase in early survivors of myocardial infarction and use of intravenous drug has the advantage of earlier and easier application. Additional studies will be required to address effects on mortality. Circulation 70, No. 4, 606-618, 1984. MYOCARDIAL INFARCTION represents the most important pathologic entity in Western society in terms of morbidity and mortality. Attempts to reduce the size of myocardial infarction with drugs that reduce myocardial functional demand have, in general, been disFrom the Department of Internal Medicine, Division of Cardiology, University of Utah School of Medicine, and LDS Hospital, Salt Lake City. Supported in part by a grant from the LDS Hospital-Deseret Foundation, Salt Lake City. Address for correspondence: Jeffrey L. Anderson, M.D., Cardiology Division, LDS Hospital, 325 Eighth Ave., Salt Lake City, UT 84143. Received March 6, 1984; revision accepted July 5, 1984. 606 appointing. ' Recently, the feasibility of restoring coronary perfusion by administration of intracoronary thrombolytic agents has been demonstrated.2`5 Results of nonrandomized studies have also suggested the possibility of cardiac functional improvement,i-'0 but controlled trials have given mixed results, reporting either no effect", 12 or a modest relative improvement in ventricular function'3 after application of streptokinase at 4 to 6 hr after onset of symptoms. Recent studies have also suggested a potential reduction in mortality in patients undergoing reperfusion with intracoronary CIRCULATION by gest on Sptem er 5, 2017 http://ciajournals.org/ D ow nladed from THERAPY AND PREVENTION-THROMBOLYSIS streptokinase.8' 12 These results are leading to more widespread application of thrombolytic therapy.'4 However, a minority of hospitals have coronary angiographic laboratories, and even these are not all prepared to provide 24 hr coverage. Moreover, it is unlikely that intracoronary administration of streptokinase at an average of less than 3 to 4 hr after onset of symptoms will be feasible. These considerations have stimulated interest in the use of short-term, relatively high-dose intravenous streptokinase.'5 Large-scale studies of effects of standard doses of intravenous streptokinase on patients with acute myocardial infarction have been performed in the past decade.'6' 1" While the relative safety of these infusions was established, the study designs were flawed and the results mixed.'8 Intravenous streptokinase has not to date been approved for general use in this application. The feasibility of coronary thrombolysis by high-dose, short-term infusion of streptokinase was recently confirmed by Schroder et al. '5 However, as with intracoronary streptokinase, randomized studies are needed to adequately assess safety and potential benefit with respect to hospital course. We recently demonstrated that early application of intracoronary streptokinase may be associated with a beneficial overall effect on in-hospital course of patients with acute myocardial infarction. 13 In an effort to allow earlier, easier application of thrombolytic therapy, we next undertook a prospective, randomized study to compare the intravenous with the intracoronary drug in treatment of patients with acute myocardial infarction. Results were also compared with those in our comparable historical control group of patients that did not receive thrombolytic therapy.