Tissue plasminogen activator: why the backlash?

Abstract

In recent months since the approval of intravenous thrombolytic agents in the United States, recombinant tissue plasminogen activator (rt-PA) has been under fire in many peer review medical journal articles (l-4). At issue is whether rt-PA, an expensive, elegant product of the molecular biology revolution, is really better than streptokinase, an inexpensive bacterial protein produced by routine laboratory methods. The cumulative data base from 13 angiographic studies (5-17) indicates that infarct vessel patency at 60 to 120 min was achieved approximately 50% more frequently with r&PA compared with streptokinase (75% versus 48%, respectively) for 1,738 patients treated at 2.9 h from symptom onset. However, a definite “catch-up” phenomenon for streptokinase has been documented (17) by serial angiography performed up to 24 h after symptom onset. By the time of late follow-up cardiac catheterization, the patency rate of arteries treated with agents lacking fibrin selectivity is similar to that of patients treated with rt-PA. Thus, although rt-PA holds promise for improved earfy coronary thrombolytic action, it has not yet been demonstrated whether this effect translates into superior preservation of left ventricular function or a reduction of mortality. Left ventricular function. In this issue of the Journal, Armstrong et al. (18), from 10 Toronto hospitals (TPAT), report a placebo-controlled trial of rt-PA in left ventricular function. It is the first study of the predominantly two chain Burroughs-Wellcome preparation of rt-PA, which has demonstrated efficacy beyond coronary thrombolysis. The dosing in megaunits per kilogram, is, however, quite different from that of most previous trials (5-8) of this fibrinolytic agent, although weight-adjusted dosing has previously been associated with improved infarct vessel patency, less reoc-