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

Abstract

Rapid and complete coronary reperfusion salvages myocardial tissue, resulting in limitation of infarct size and accelerated release of proteins from the myocardium. Treatment with tissue plasminogen activator, resulting in earlier reperfusion was more effective in reducing infarct size than the streptokinase regimens, which contributes to the differences in survival between treatment groups in the GUSTO trial.

Dependency on Infarct Size Limits the Clinical Applicability of Non-Invasive Reperfusion Assessment by Biochemical Markers in Acute Myocardial Infarction

“…One would also expect reperfusion assessment to correlate with outcome, as patency of the infarct-related artery on 90-min coronary angiography does so [1,4,17]. Finally, one would expect an inverse correlation between enzymatic infarct size and the reperfusion indexes, as reperfusion is supposed to salvage jeopardised myocardium [3,18]. We actually found a significant inverse correlation between enzymatic infarct size and ST recovery 0-90 .…”

“…Or it could reflect a systematic underestimation of enzymatic infarct size in non-reperfused patients due to subtotal recovery of enzyme activity in blood. The GUSTO substudies, however, speak strongly against these explanations, as improved TIMI flow was associated with smaller enzymatic infarct size [3], better preserved LVEF, and lower mortality rates [1]. Also the APSAC study reported smaller enzymatic infarct size in case of reperfusion [19].…”

“…Blood was collected immediately before initiation of thrombolytic treatment and after 45 and 90 min, 3,6,12,20,36, and 52 h. The ECG was repeated after 90 and 180 min. Discharge diagnosis was established by independent cardiologists according to WHO criteria [12] using creatine kinase (CK), CK-B, and lactate dehydrogenase isoenzyme 1 (LD1) as routine coronary enzymes.…”

“…The GUSTO Angiographic Substudy [1], however, revealed that patency in terms of TIMI 2-3 flow [2] was only obtained in 54-81% of the patients 90 min after start of treatment. A close relationship appeared between TIMI flow at 90 min coronary angiography and short-term as well as long-term outcome (smaller final infarct size [3], better preserved left ventricular function and improved 30-day [1] as well as 5-year survival [4] in reperfused patients).…”

Effect of Pexelizumab, an Anti-C5 Complement Antibody, as Adjunctive Therapy to Fibrinolysis in Acute Myocardial Infarction

“…Infarct size measured by serial CK-MB assessment correlates with left ventricular failure, 23,24 presence of Q waves, 25 and mortality, 24 -26 although these findings are debated. Nevertheless, cardiac-enzyme release has been used to show a reduction in infarct size by streptokinase treatment versus placebo, 27 alteplase versus streptokinase, 28 and angioplasty versus streptokinase. 29 Such surrogates are useful for establishing proof of concept for new therapies but have inherent limitations in predicting treatment effect on clinical outcomes.…”