Coronary thrombolysis mortality trials

Gore JM, Granger CB, Simoons ML, Sloan MA, Weaver WD, White HD, Barbash Gl, Van de Werf F, Aylward PE, Topol FJ, et al. Stroke after thrombolysis. Mortality and functional outcomes in the GUSTO-I trial. Global Use of Strategies To Open Occluded Coronary Arteries. Circulation. 1995 92 2811-2818. 

Section I of this book describes 1) the conceptual basis underlying pharmacoinvasive therapy, 2) the efficacy and limitations of each of its two components when used alone, and 3) the reductions in mortality that have been accomplished with each. Section II addresses the failure of early trials to demonstrate the benefit of combinations of balloon angioplasty coupled with antecedent coronary thrombolysis. 

Regardless of the nature of the endpoint used, the rapidity of coronary reperfusion was found to be of paramount importance (14,19,32-36,67-69). As much as 80% of the potential benefit conferred by coronary reperfusion via thrombolysis was found to be lost when reperfiision was delayed for as little as 3 hours following the onset of ischemic injury (32). Although some controversy exists with respect to file influence of early reperfusion on mortality after primary PCI (33,69), data from both multicenter trials and registries are consistent with increased mortality associated with delays in initiation of primary PCI (Fig. 1.4) (34-36,53). 

The GUSTO trial demonstrated that treatment of patients within 6 hours after onset of symptoms with the combination of a clot-selective thrombolytic agent [recombinant tissue type plasminogen activator (t-PA)] plus conjunctive treatment with aspirin and intravenous unfractionated heparin resulted in 30-day mortality of 6.3% (6). An angiographic substudy demonstrated that patency of the infarct-related artery was not the sole determinant of outcome. Restoration of normal coronary flow after thrombolysis was found to be critical in lowering mortality (7). Thus, angiographic analysis demonstrated that both induction of culprit artery patency and the extent of restoration of flow were determinants of outcome. 

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