Thrombolysis for Acute Myocardial Infarction: Drug Review

David K. Cundiff

Disclosures
In This Article

Thrombolytic Therapy in Patients Without AMI

The hospital mortality of patients with unstable angina is about 1%,[41] which is about the fatal complication rate with thrombolysis. Consequently, it is hard to see how thrombolysis could improve survival in unstable angina. In a randomized study by Freeman and colleagues[42] looking at thrombolysis given to patients with unstable angina, infusion of t-PA lysed intracoronary thrombi but did not significantly decrease in-hospital cardiac events. They found a paradoxic increase in ST shift and worsening of myocardial perfusion with t-PA compared with therapy with heparin alone.[42]

Schreiber and colleagues[43] reported on a randomized comparison of urokinase (UK) vs placebo in patients with unstable angina who were also receiving aspirin and/or heparin. A trend appeared suggesting increased death and other adverse cardiac events with UK, so the investigators canceled a planned extension of the trial. Due to these poor results, the guidelines of the Agency of Healthcare Policy and Research specified in 1994 that thrombolysis should not be given to patients with unstable angina.[44]

All of the major trials of thrombolytic therapy included patients with chest pain that turned out not to be due to a transmural AMI. For instance, in the most recent trials, Estudio Multicentrico Estreptoquinasa Republicas de America del Sur (EMERAS) and Late Assessment of Thrombolytic Efficacy (LATE), in which relatively sophisticated diagnostic assays for rapid confirmation of AMI were available, AMI could be confirmed in only 89% and 93% of the patients respectively.[16,17] So even in tightly monitored clinical research studies, the risks of thrombolysis, including fatal complications, were imposed on people who would not benefit from and may be harmed by the therapy. For instance, the mistaken use of thrombolytic medication in patients with dissecting aortic aneurysm and pericarditis has been reported, sometimes with fatal consequences.[45] We might expect that, in general clinical practice, a higher percentage of noncandidates for thrombolysis might be inadvertently treated.

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