DIFFERENTIAL-EFFECTS OF TISSUE-PLASMINOGEN ACTIVATOR AND STREPTOKINASE ON INFARCT SIZE AND ON RATE OF ENZYME-RELEASE - INFLUENCE OF EARLY INFARCT-RELATED ARTERY PATENCY - THE GUSTO ENZYME SUBSTUDY

Background The recent international GUSTO trial of 41 021 patients wit h acute myocardial infarction demonstrated improved 90-min infarct rel ated artery patency as well as reduced mortality in patients treated w ith an accelerated regimen of tissue plasminogen activator, compared t o patients treated with streptokinase. A regimen combining tissue plas minogen activator and streptokinase yielded intermediate results. The present study investigated the effects of treatment on infarct size an d enzyme release kinetics in a subgroup of these patients. Methods A t otal of 553 patients from 15 hospitals were enrolled in the study. Fou r thrombolytic strategies were compared: streptokinase with subcutaneo us heparin, streptokinase with intravenous (i.v.) heparin, tissue plas minogen activator with i.v. heparin, and streptokinase plus tissue pla sminogen activator with i.v. heparin. The activity of alpha-hydroxybut yrate dehydrogenase (HBDH) in plasma was centrally analysed and infarc t size was defined as cumulative HBDH release per litre of plasma with in 72 h of the first symptoms (Q(72)). Patency of the infarct-related vessel was determined by angiography in 159 patients, 90 min after tre atment. Results Infarct size was 3.72 g-eq.l(-1) in patients with adeq uate coronary perfusion (TIMI-S) at the 90 min angiogram and larger in patients with TIMI-2 (4.35 g-eq.l(-1)) or TIMI 0-1 (5.07 g-eq.l(-1)) flow (P = 0.024). In this subset of the GUSTO angiographic study, earl y coronary patency rates (TIMI 2 + 3) were similar in the two streptok inase groups (53 and 46%). Higher, but similar, patency rates were obs erved in the tissue plasminogen activator and combination therapy grou ps (87 and 90%). Median infarct size for the four treatment groups, ex pressed in gram-equivalents (g-eq) of myocardium, was 4.4, 4.5, 3.9 an d 3.9 g-eq per litre of plasma (P = 0.04 for streptokinase vs tissue p lasminogen activator). Six hours after the first symptoms, respectivel y 5.3, 6.6, 14.0 and 13.6% of total HBDH release was complete (P < 0.0 001 for streptokinase vs tissue plasminogen activator). Conclusions Ra pid and complete coronary reperfusion salvages myocardial tissue, resu lting in limitation of infarct size and accelerated release of protein s from the myocardium. Treatment with tissue plasminogen activator, re sulting in earlier reperfusion was more effective in reducing infarct size than the streptokinase regimens, which contributes to the differe nces in survival between treatment groups in the GUSTO trial.