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Twenty-four patients with unstable angina pectoris, defined as chest pain at rest with transient ST segment deviation of at least 1 mm, were randomly assigned to blinded treatment with either placebo or intravenous recombinant human tissue-type plasminogen activator (rt-PA). Before randomization, all patients were treated with oral 13-blockers, calcium antagonists, nitrates, and continuous intravenous heparin for a monitoring period of 12 to 28 hr. After this monitoring period the 24 patients were randomly assigned to receive either placebo or 1.75 mg/kg intravenous rt-PA given over 12 hr at a rate of 0.75 mg/kg over 1 hr, 0.5 mg/kg over 4 hr, and 0.5 mg/kg over 7 hr. One patient, assigned to receive placebo, developed acute myocardial infarction after randomization but before receiving the study drug. Ischemic events were recorded during a hospital follow-up period of at least 4 days unless a further intervention was indicated or the coronary angiogram was normal. The follow-up period was 7 5 days (mean + SD) after the placebo infusion and 8 ± 4 days after the infusion of rt-PA. Unstable angina pectoris persisted after the completion of the infusion in six of 11 patients receiving placebo and only one of 12 patients receiving rt-PA (p < .03). Coronary angiography, performed 38 ± 19 hr after the infusion, demonstrated subocclusive thrombus in eight of 11 patients receiving placebo but in none of 11 patients treated with rt-PA (p < .002). One patient on rt-PA refused coronary angiography. Persistence of unstable angina pectoris correlated significantly with the presence of intracoronary thrombus (p < .003). The infusion of rt-PA caused a decrease of fibrinogen to 66 ± 19% after 1 hr, to 65 ± 21% after 5 hr, and to 64 ± 29% after 12 hr. Oozing at puncture sites was not observed in patients receiving placebo but was seen in eight of 12 patients treated with rt-PA. In three patients on rt-PA, bleeding complications necessitated termination of the infusion within 5, 8, and 11 hr after onset. Thus, in this group of patients with unstable angina pectoris, intravenous infusion of rt-PA appeared to lyse subocclusive intracoronary thrombi. The removal of intracoronary thrombus by rt-PA was associated with reduction of the severity of resting angina. The decision for further intervention could then be made on the basis of residual coronary occlusion.

SUMMARY A multicentred, randomised, blind study was started in 1978 to compare propranolol or hyaluronidase with placebo in patients with acute myocardial infarction admitted within 18 hours of onset of symptoms. Patients were randomised to group A and received hyaluronidase, propanolol, or placebo, or, if propranolol was contraindicated, to group B and received hyaluronidase or placebo. Hyaluronidase (500 U/kg given every six hours for 48 hours) had no effect on mortality or infarct size in the overall population. Because spontaneous reperfusion was more common in patients with early peaking of plasma creatine kinase MB or non-transmural electrocardiographic changes or both, the results were reanalysed for two subgroups: those in whom plasma creatine kinase peaked < 15 hours after the onset of symptoms (early peak, n = 184) and those with a peak > 15 h after the onset of symptoms (late peak, n = 546). The distribution of time to peak activity of creatine kinase MB was similar in the hyaluronidase and placebo groups. In the early peak patients who were given hyaluronidase (groups A and B) total mortality and cardiacspecific four year mortality were significantly lower. This was most pronounced in group B in which the total mortality was 45% and cardiovascular mortality was 47% less than in the placebo group. Similarly, mortality from cardiovascular disease in patients (groups A and B) with nontransmural ischaemia (ST-T changes) given hyaluronidase was significantly lower, with

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