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 improves su rvival after acute myocardial infarction, it has been debated whether the speed with which coronary-artery patency is restored after the ini tiation of therapy further affects outcome. Methods. To study this que stion, we randomly assigned 2431 patients to one of four treatment str ategies for reperfusion: streptokinase with subcutaneous heparin; stre ptokinase with intravenous heparin; accelerated-dose tissue plasminoge n activator (t-PA) with intravenous heparin; or a combination of both activators plus intravenous heparin. Patients were also randomly assig ned to cardiac angiography at one of four times after the initiation o f thrombolytic therapy: 90 minutes, 180 minutes, 24 hours, or 5 to 7 d ays. The group that underwent angiography at 90 minutes underwent it a gain after 5 to 7 days. Results. The rate of patency of the infarct-re lated artery at 90 minutes was highest in the group given accelerated- dose t-PA and heparin (81 percent), as compared with the group given s treptokinase and subcutaneous heparin (54 percent, P<0.001), the group given streptokinase and intravenous heparin (60 percent, P<0.001), an d the group given combination therapy (73 percent, P = 0.032). Flow th rough the infarct-related artery at 90 minutes was normal in 54 percen t of the group given t-PA and heparin but in less than 40 percent of t he three other groups (P<0.001). By 180 minutes, the patency rates wer e the same in the four treatment groups. Re-occlusion was infrequent a nd was similar in all four groups (range, 4.9 to 6.4 percent). Measure s of left ventricular function paralleled the rate of patency at 90 mi nutes; ventricular function was best in the group given t-PA with hepa rin and in patients with normal flow through the infarct-related arter y irrespective of treatment group. Mortality at 30 days was lowest (4. 4 percent) among patients with normal coronary flow at 90 minutes and highest (8.9 percent) among patients with no flow (P = 0.009). Conclus ions. This study supports the hypothesis that more rapid and complete restoration of coronary flow through the infarct-related artery result s in improved ventricular performance and lower mortality among patien ts with myocardial infarction. This would appear to be the mechanism b y which accelerated t-PA therapy produced the most favorable outcome i n the GUSTO trial.