Intravenous administration of 80 mg of recombinant tissue plasminogen activator (rt-PA, 40, 20, and 20 mg in successive hours) and streptokinase (SK, 1.5 million units over 1 hr) was compared in a double-blind, randomized trial in 290 patients with evolving acute myocardial infarction. These patients entered the trial within 7 hr of the onset of symptoms and underwent baseline coronary arteriography before thrombolytic therapy was instituted. Ninety minutes after the start of thrombolytic therapy, occluded infarct-related arteries had opened in 62% of 113 patients in the rt-PA and 31% of 119 patients in the SK group (p less than .001). Twice as many occluded infarct-related arteries opened after rt-PA compared with SK at the time of each of seven angiograms obtained during the first 90 min after commencing thrombolytic therapy. Regardless of the time from onset of symptoms to treatment, more arteries were opened after rt-PA than SK. The reduction in circulating fibrinogen and plasminogen and the increase in circulating fibrin split products at 3 and 24 hr were significantly less in patients treated with rt-PA than in those treated with SK (p less than .001). The occurrence of bleeding events, administration of blood transfusions, and reocclusion of the infarct-related artery was comparable in the two groups. Thus, in patients with acute myocardial infarction, rt-PA elicited reperfusion in twice as many occluded infarct-related arteries as compared with SK at each of seven serial observations during the first 90 min after onset of treatment.

Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge.

The clinical management of acute myocardial infarction and crescendo angina as well as the prevention of sudden ischaemic death require accurate knowledge of the underlying arterial pathology. It is on just this aspect that until recently there has been disagreement particularly among pathologists. In brief, this controversy was concerned with whether coronary artery thrombi were or were not directly responsible for all three clinical pictures of acute ischaemia. Resolution of the controversy has been derived from coronary angiography in life in patients with acute infarction and crescendo angina and from detailed pathological studies. These latter studies differ from many carried out previously by the use of postmortem coronary angiography and histological reconstruction of the microanatomy of occlusive lesions.

https://heart.bmj.com/content/heartjnl/53/4/363.full.pdf

Plaque fissuring--the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina.

We randomly assigned 56 patients who presented within 12 hours of their first symptoms of acute myocardial infarction to treatment with either intracoronary streptokinase or coronary angioplasty. The mean (±SD) duration of symptoms (3.0±1.2 hours in the group treated with angioplasty vs. 3.6±1.8 in the group treated with streptokinase; P not significant) and time to recanalization (4.1±1.4 hours vs. 4.8±1.7 hours; P not significant) were similar in both groups. Coronary recanalization was achieved in 83 percent of the patients treated with angioplasty and in 85 percent of those treated with streptokinase (P not significant). Residual luminal stenosis in the coronary artery was significantly decreased after angioplasty, as compared with streptokinase therapy (43±31 percent of patients vs. 83±17; P<0.001). Residual stenosis of 70 percent or more was present in 4 percent of the angioplasty-treated patients and in 83 percent of the streptokinase-treated patients (P<0.01). Ventricular function after t...

A prospective randomized clinical trial of intracoronary streptokinase versus coronary angioplasty for acute myocardial infarction.

IMPROVED SURVIVAL AFTER EARLY THROMBOLYSIS IN ACUTE MYOCARDIAL INFARCTION: A Randomised Trial by the Interuniversity Cardiology Institute in The Netherlands

In Phase I of the NHLBI trial of Thrombolysis in Myocardial Infarction (TIMI), 290 patients admitted within 7 hr after onset of acute infarction were randomly assigned to intravenous treatment with either streptokinase (SK) or recombinant tissue-type plasminogen activator (rt-PA). Left ventricular function was measured from contrast ventriculograms in 145 patients with both pretreatment and predischarge studies analyzable. Regional wall motion in the infarct site was measured by the centerline method and expressed in units of standard deviations (SDs) from the mean motion in 52 normal subjects. Patients treated with rt-PA (n = 77) achieved a significantly higher reperfusion rate after 90 min of treatment. Perfusion of the infarct-related artery improved from visual grade 0 or 1 (total occlusion or penetration without perfusion) to grade 2 or 3 (partial or full reperfusion) in 62% receiving rt-PA vs 31% receiving SK (n = 68) (p less than .001). However, the ejection fraction did not change significantly from before treatment to before discharge in either treatment group (+0.7 +/- 6.7% vs +1.0 +/- 8.3%, respectively). A small but significant increase in regional wall motion was observed in each of the two groups (+0.4 +/- 0.8 vs +0.3 +/- 0.8 SD/chord, respectively; each p less than .001 compared with baseline). This was countered by declines in the hyperkinesis of the noninfarct region (-0.3 +/- 1.0 SD/chord [p = .01] compared with baseline and -0.2 +/- 1.0 SD/chord [p = .23], respectively). Analysis of the combined groups revealed that the ejection fraction increased only in patients who achieved reperfusion by 90 min after onset of therapy or who had subtotal occlusions initially. There was greater recovery of left ventricular function in patients who achieved reperfusion earlier vs later than 4 hr after symptom onset and in patients with vs without some collateral circulation to the infarct-related artery.

The effect of intravenous thrombolytic therapy on left ventricular function: a report on tissue-type plasminogen activator and streptokinase from the Thrombolysis in Myocardial Infarction (TIMI Phase I) trial.

High-dose, brief intravenous streptokinase early in acute myocardial infarction

Coronary arteriography was performed before, immediately after, and 9 to 14 days after administering i.v. Streptokinase (850,000 to 1,500,000 IU) to 43 patients within 6 hours of myocardial infarction. Ventricular function was determined by contrast ventriculography before and 9 to 14 days later and by radionuclide studies at clinical follow-up 8 months later. Early reperfusion occurred in 49% of patients, but in only 35 % was it sustained. In patients with sustained reperfusion, early ventricular dysfunction was significantly reduced 9 to 14 days and 10 months later, and frequency of infarction, sudden death, and angina pectoris was not increased at follow-up. No serious bleeding occurred.

Coronary thrombolysis by intravenous streptokinase in acute myocardial infarction: Acute and follow-up studies☆

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High-dose, brief intravenous streptokinase early in acute myocardial infarction

Coronary thrombolysis by intravenous streptokinase in acute myocardial infarction: Acute and follow-up studies☆