The Effects of Tissue Plasminogen Activator, Streptokinase, or Both on Coronary-Artery Patency, Ventricular Function, and Survival after Acute Myocardial Infarction
Background Although it is known that thrombolytic therapy improvessurvival after acute myocardial infarction, it has been debatedwhether the speed with which coronary-artery patency is restoredafter the initiation of therapy further affects outcome.
Methods To study this question, we randomly assigned 2431 patientsto one of four treatment strategies for reperfusion: streptokinasewith subcutaneous heparin; streptokinase with intravenous heparin;accelerated-dose tissue plasminogen activator (t-PA) with intravenousheparin; or a combination of both activators plus intravenousheparin. Patients were also randomly assigned to cardiac angiographyat one of four times after the initiation of thrombolytic therapy:90 minutes, 180 minutes, 24 hours, or 5 to 7 days. The groupthat underwent angiography at 90 minutes underwent it againafter 5 to 7 days.
Results The rate of patency of the infarct-related artery at90 minutes was highest in the group given accelerated-dose t-PAand heparin (81 percent), as compared with the group given streptokinaseand subcutaneous heparin (54 percent, P<0.001), the groupgiven streptokinase and intravenous heparin (60 percent, P<0.001),and the group given combination therapy (73 percent, P = 0.032).Flow through the infarct-related artery at 90 minutes was normalin 54 percent of the group given t-PA and heparin but in lessthan 40 percent of the three other groups (P<0.001). By 180minutes, the patency rates were the same in the four treatmentgroups. Reocclusion was infrequent and was similar in all fourgroups (range, 4.9 to 6.4 percent). Measures of left ventricularfunction paralleled the rate of patency at 90 minutes; ventricularfunction was best in the group given t-PA with heparin and inpatients with normal flow through the infarct-related arteryirrespective of treatment group. Mortality at 30 days was lowest(4.4 percent) among patients with normal coronary flow at 90minutes and highest (8.9 percent) among patients with no flow(P = 0.009).
Conclusions This study supports the hypothesis that more rapidand complete restoration of coronary flow through the infarct-relatedartery results in improved ventricular performance and lowermortality among patients with myocardial infarction. This wouldappear to be the mechanism by which accelerated t-PA therapyproduced the most favorable outcome in the GUSTO trial.
Source Information
Dr. Ross, as chairman of the GUSTO Angiographic Study, assumes full responsibility for the overall content and integrity of the manuscript.A list of the GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) angiographic investigators appears in the Appendix.
Address reprint requests to Dr. Allan M. Ross at the Division of Cardiology, George Washington University, 2150 Pennsylvania Ave., NW, Washington, DC 20037.
Authors/Task Force Members, , Van de Werf, F., Bax, J., Betriu, A., Blomstrom-Lundqvist, C., Crea, F., Falk, V., Filippatos, G., Fox, K., Huber, K., Kastrati, A., Rosengren, A., Steg, P. G., Tubaro, M., Verheugt, F., Weidinger, F., Weis, M., ESC Committee for Practice Guidelines (CPG), , Vahanian, A., Camm, J., De Caterina, R., Dean, V., Dickstein, K., Filippatos, G., Funck-Brentano, C., Hellemans, I., Kristensen, S. D., McGregor, K., Sechtem, U., Silber, S., Tendera, M., Widimsky, P., Zamorano, J. L., Document Reviewers, , Silber, S., Aguirre, F. V., Al-Attar, N., Alegria, E., Andreotti, F., Benzer, W., Breithardt, O., Danchin, N., Mario, C. D., Dudek, D., Gulba, D., Halvorsen, S., Kaufmann, P., Kornowski, R., Lip, G. Y. H., Rutten, F.
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