Barbara F. Williams

Prospective evaluation of eligibility for thrombolytic therapy in acute myocardial infarction.

Abstract Objective: To determine the proportion of patients presenting with acute myocardial infarction who are eligible for thrombolytic therapy. Design: Cohort follow up study. Setting: The four coronary care units in Auckland, New Zealand. Subjects: All 3014 patients presenting to the units with suspected myocardial infarction in 1993. Main outcome measures: Eligibility for reperfusion with thrombolytic therapy (presentation within 12 hours of the onset of ischaemic chest pain with ST elevation >/=2 mm in leads V1-V3, ST elevation >/=1 mm in any other two contiguous leads, or new left bundle branch block); proportions of (a) patients eligible for reperfusion and (b) patients with contraindications to thrombolysis; death (including causes); definite myocardial infarction. Results: 948 patients had definite myocardial infarction, 124 probable myocardial infarction, and nine ST elevation but no infarction; 1274 patients had unstable angina and 659 chest pain of other causes. Of patients with definite or probable myocardial infarction, 576 (53.3%) were eligible for reperfusion, 39 had definite contraindications to thrombolysis (risk of bleeding). Hence 49.7% of patients (537/1081) were eligible for thrombolysis and 43.5% (470) received this treatment. Hospital mortality among patients eligible for reperfusion was 11.7% (55/470 cases) among those who received thrombolysis and 17.0% (18/106) among those who did not. Conclusions: On current criteria about half of patients admitted to coronary care units with definite or probable myocardial infarction are eligible for thrombolytic therapy. Few eligible patients have definite contraindications to thrombolytic therapy. Mortality for all community admissions for myocardial infarction remains high. Key messages Less than 10% of patients eligible for reperfusion have contraindications to thrombolysis The hospital mortality for all patients with acute myocardial infarction remains high (14%) Better treatments are required to reduce mortality in both reperfusion eligible and reperfusion ineligible patients

Frequent reocclusion of patent infarct-related arteries between 4 weeks and 1 year: Effects of antiplatelet therapy

OBJECTIVES This study assessed the effect of the combination of aspirin and dipyridamole on patency of the infarct-related artery between 4 weeks and 1 year after myocardial infarction. BACKGROUND Patency of the infarct-related artery is an important determinant of prognosis after myocardial infarction. The incidence of late reocclusion and the effects of antiplatelet therapy are unknown. METHODS To investigate the importance of antiplatelet therapy for the prevention of late reocclusion, 215 patients who had a patent infarct-related artery 4 weeks after myocardial infarction were randomized in a double-blind manner to receive either a combination of 25 mg of aspirin and 200 mg of dipyridamole twice daily or placebo. One hundred fifty-four patients underwent further coronary arteriography 1 year later. RESULTS At 1 year, 38 (25%) of 154 patients had reocclusion of the infarct-related artery; 18 (23%) of 79 patients receiving aspirin and dipyridamole had late reocclusion versus 20 (27%) of 75 who received placebo (p = NS). The rate of reocclusion was related to the severity of the residual coronary artery stenosis at 4 weeks (< 50% stenosis 9.2%; 50% to 69% stenosis 11.6%; 70% to 89% stenosis 30.4%; > or = 90% stenosis 70%, p < 0.01). The majority of reocclusions were silent, and only 17 (45%) of 38 were clinically associated with further infarction. There were no differences for a hierarchic end point of cardiac death, myocardial infarction or revascularization (14.8% aspirin and dipyridamole vs. 17.8% placebo). CONCLUSIONS Late reocclusion of the patent infarct-related artery is a frequent event, occurring in 25% of patients. Antiplatelet therapy with the combination of aspirin and dipyridamole does not alter the overall rate of late reocclusion. Other strategies are required to reduce late reocclusion.

Reinfarction after thrombolytic therapy for acute myocardial infarction followed by conservative management : incidence and effect of smoking

A group of 456 consecutive patients seen less than or equal to 6 h after the onset of acute myocardial infarction associated with ST segment elevation received thrombolytic therapy and were followed up for 12 months. Intravenous streptokinase was given to 315 patients and recombinant tissue-type plasminogen activator (rt-PA) to 141 patients. Reinfarction rate and risk factors for reinfarction were assessed. Management after thrombolysis was conservative; revascularization procedures were reserved for patients with symptoms refractory to medical therapy or for those with left main coronary artery stenosis. Coronary artery surgery or angioplasty was performed in only 3.7% of patients during the first 30 days after thrombolysis and in only 8.6% by 1 year. Most patients (79%) underwent coronary arteriography. Twenty-six patients (5.7%) exhibited signs of threatened reinfarction at 1 month after thrombolytic therapy as did 43 patients (9.4%) by 1 year. Reinfarction was prevented in four of these patients by early readministration of thrombolytic therapy. Multivariate analysis of possible risk factors for reinfarction identified at the time of initial infarction showed current cigarette smoking to be the only predictive factor (reinfarction occurred in 12.5% of smokers versus 6.3% of nonsmokers, p = 0.04). A second analysis of risk factors identified 3 weeks after initial infarction, including the severity of residual stenosis at coronary arteriography and exercise test variables, again showed continued cigarette smoking to be the only factor predictive of reinfarction. Twenty percent of patients who continued to smoke developed reinfarction compared with 5.1% of those who stopped (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Safety and efficacy of repeat thrombolytic treatment after acute myocardial infarction.

Thrombolytic treatment for acute myocardial infarction increases the risk of subsequent reocclusion of the infarct related artery. The efficacy and safety of repeat thrombolytic treatment was assessed in 31 patients treated with streptokinase (n = 13) or tissue plasminogen activator (n = 18) a median of five days (1-716) after the first infusion. The indication for readministration was prolonged chest pain with new ST segment elevation. Efficacy was assessed by infarct artery patency at angiography at a median of eight days after readministration in 22 patients and by non-invasive criteria in 23 patients (reperfusion was deemed to be likely if serum creatine kinase was not increased or reached a peak less than 12 hours after infarction). Angiography showed patency of 70% of the infarct arteries after readministration of streptokinase and of 75% after tissue plasminogen activator. The corresponding patency rates assessed noninvasively were 73% and 75%. Reinfarction was prevented in nine (29%) patients. Allergic reactions occurred in four of eight patients who received streptokinase twice (plasmacytosis and acute reversible renal failure developed in one patient). Two patients had major bleeding and two minor bleeding, all after tissue plasminogen activator, and one of them died of cerebral haemorrhage. Repeat thrombolytic treatment results in late patency rates similar to the rates after the initial administration. Allergic reactions were common in those treated twice with streptokinase.

Abnormal Coronary Flow in Infarct Arteries 1 Year After Myocardial Infarction Is Predicted at 4 Weeks by Corrected Thrombolysis in Myocardial Infarction (TIMI) Frame Count and Stenosis Severity

Because 24% to 30% of patent infarct-related arteries occlude in the year following thrombolytic therapy for acute myocardial infarction, angiographic factors including corrected Thrombolysis in Myocardial Infarction (TIMI) frame count which may predict abnormal infarct-artery flow, require definition. We examined changes in coronary flow and infarct-artery lesion severity by computerized quantitative angiography over 1 year in 154 patients with a patent infarct-related artery 4 weeks after myocardial infarction. These patients were randomized to receive either ongoing daily therapy of 50 mg aspirin and 400 mg dipyridamole, or placebo. All angiograms were interpreted blind in our core angiographic laboratory. Infarct-artery flow, assessed by corrected TIMI frame counts, was normal (< or = 27) in 46% and 45% of patients at 4 weeks and 1 year, respectively. At 4 weeks, patients with corrected TIMI frame counts < or = 27 had higher ejection fractions (60+/-11% vs 56+/-12%; p = 0.04) than those with corrected TIMI frame counts >27. On multivariate analysis, corrected TIMI frame count and stenosis severity were predictive of late abnormal infarct-artery flow (TIMI 0 to 2 flow, both p <0.01). Only stenosis severity at 4 weeks predicted reocclusion at 1 year (p <0.0001). Aspirin and dipyridamole had no effect on flow or reocclusion. Thus, corrected TIMI frame count and stenosis severity at 4 weeks was highly correlated with infarct-artery flow at 1 year.

Angiographic frame counts 90 minutes after streptokinase predict left ventricular function at 48 hours following myocardial infarction.

Objective To assess whether the 90 minute corrected thrombolysis in myocardial infarction frame count (CTFC) in the infarct related artery predicts left ventricular function at 48 hours in patients with myocardial infarction treated with aspirin, streptokinase, and either heparin or Hirulog. Design and setting Analysis of 251 patients with acute myocardial infarction enrolled in the international, multicentre Hirulog early reperfusion/occlusion (HERO-1) trial, who underwent both 90 minute coronary angiography and 48 hour left ventriculography. Main outcome variables The CTFC was determined in the infarct related artery 90 minutes after starting intravenous streptokinase (1.5 × 106 U over 30 to 60 minutes), and compared with indices of left ventricular function assessed by contrast ventriculography at 48 hours. Results A CTFC of ⩽ 27 frames (previously reported mean + 2 SD in coronary arteries of patients without acute infarction) occurred in 29% of infarct related arteries, and was associated with a lower infarct zone mean chord score (−2.06 v −2.54, p = 0.01), a lower fraction of chords > 2 SD below normal (37%v 51%, p = 0.005), and trends towards higher left ventricular ejection fractions (60.9%v 58.2%, p = 0.11) and lower end systolic volumes (50.1 ml v 55.9 ml, p = 0.23). A CTFC of ⩽ 40 at 90 minutes occurred in 50% of infarct related arteries, and was associated with a significantly lower mean chord score (−2.20 v −2.60, p = 0.02), a smaller fraction of chords > 2 SD below normal (41%v 52%, p = 0.025), a smaller end systolic volume (49.1 ml v 59.3 ml, p = 0.02), and a higher left ventricular ejection fraction (60.4%v 56.5%, p = 0.03). Conclusions The 90 minute CTFC predicts left ventricular function at 48 hours following streptokinase. The CTFC associated with better ventricular function may be higher than values determined from a non-infarct population.

Effects of early captopril administration after Thrombolysis on regional wall motion in relation to infarct artery blood flow

OBJECTIVES To determine whether early administration of captopril lessens infarct zone regional wall motion abnormalities when infarct artery blood flow is abnormal. BACKGROUND The interaction between angiotensin-converting enzyme (ACE) inhibitor therapy, ventricular function and infarct artery blood flow has not been well described. METHODS A total of 493 patients aged < or = 75 years with first infarctions, presenting within 4 h of symptom onset, were randomized to receive 6.25 mg captopril, increasing to 50 mg t.d.s. or a matching placebo 2.1+/-0.4 h after commencing intravenous streptokinase (1.5 x 10(6) U over 30 to 60 min). Trial therapy was stopped 48 h prior to angiography at 3 weeks, to determine regional wall motion and infarct artery flow. RESULTS There were no differences in ejection fractions or end-systolic volumes between patients randomized to receive captopril and those randomized to receive a placebo. Among patients with anterior infarction (n = 216), randomization to captopril resulted in fewer hypokinetic chords (40+/-13; vs. 44+/-13; p=0.028) and a trend toward fewer chords >2 SD below normal (26+/-17 vs. 30+/-17; p=0.052) in the infarct zone. In patients randomized to receive captopril who had anterior infarction and Thrombolysis in Myocardial Infarction (TIMI) 0-2, flow there were fewer hypokinetic chords (44+/-12 vs. 50+/-9; p=0.043) and a trend toward fewer chords >2 SD below normal (33+/-15 vs. 39+/-13; p=0.057). Patients receiving captopril who had anterior infarction and corrected TIMI frame counts > 27 had fewer hypokinetic chords (42+/-13 vs. 46+/-12; p=0.015) and fewer chords >2 SD below normal (27+/-17 vs. 32+/-17; p= 0.047). Captopril had no effect in patients with inferior infarction. There were 20 late cardiac deaths (median follow-up 4 years) in the captopril group and 35 in the placebo group (p=0.036). CONCLUSIONS Randomization to receive captopril 2 h after streptokinase improved regional wall motion at 3 weeks. The greatest benefit was seen in patients with anterior infarction particularly when infarct artery blood flow is reduced.

Effects of streptokinase in patients presenting within 6 hours of prolonged chest pain with ST segment depression.

BACKGROUND--The effects of streptokinase on the occurrence of a combined clinical outcome in patients presenting with recent chest pain and ST depression were investigated in view of the role of thrombus in the pathogenesis of acute ischaemic syndromes. METHODS--112 patients aged < or = 75 years presenting within 6 h of the last episode of ischaemic chest pain of least 20 min duration with > or = 1 mm ST depression were randomised in a double blind manner to receive either streptokinase 1.5 million units over 30 min (n = 57) or placebo (n = 55). The primary end point was the combination of death, frequency of myocardial infarction (defined as peak creatine kinase > 600 U/ml), need for angiography because of uncontrollable ischaemia, and an exercise test within 35 days showing > or = 1 mm ST depression at < or = 6 min. The secondary end points were safety, frequency of chest pain, readmission with myocardial infarction or unstable angina, or need for revascularisation between 35 days and 1 year. The severity of ST depression on presentation was analysed with respect to clinical outcome. RESULTS--The frequency of the combined hierarchical end point of death, myocardial infarction, early angiography, and a positive exercise test was 82% (47 of 57 patients) with streptokinase and 75% (41 of 55 patients) with placebo. There were four deaths, two in each group. 27 patients (47%) receiving streptokinase and 22 (40%) receiving placebo developed myocardial infarction. 11 patients (eight streptokinase and three placebo) required coronary arteriography and subsequent revascularisation because of angina uncontrolled by medical treatment. 44 patients (22 in each group) had a positive exercise test. There were three further cardiac deaths (one streptokinase, two placebo), and three noncardiac deaths within 1 year. A conservative approach to intervention was adopted and over a period of 1 year 29 patients (26%) (13 streptokinase and 16 placebo) underwent revascularisation procedures. Three patients (two streptokinase and one placebo) required transfusion. ST depression > or = 3 mm had 90% specificity but only 60% positive predictive value for myocardial infarction at presentation (P = 0.008, stepwise logistic regression). ST depression > or = 2 mm was predictive of death, late development of myocardial infarction, or a need for angiography (P = 0.02). CONCLUSION--Patients presenting with ischaemic chest pain and ST depression frequently develop myocardial infarction. Severe ST depression is predictive of an adverse outcome. The 35 day (3.6% cardiac and total) and 1 year mortality (8.9% total, 6.3% cardiac) are low with conservative management and expeditious revascularisation. Streptokinase treatment within 6 h of the last episode of pain does not seem to be beneficial.

“Rescue” thrombolysis with intracoronary tissue plasminogen activator for failed intravenous thrombolysis with streptokinase for acute myocardial infarction

Abstract Rescue thrombolysis appears to be safe and may be an alternative to angioplasty when normal epicardial blood flow is not achieved after administration of thrombolytic therapy in patients with acute myocardial infarction. Further trials are required to evaluate this approach.

Aspirin does not improve early arterial patency after streptokinase treatment for acute myocardial infarction.

OBJECTIVE--To investigate the hypothesis that the magnitude of the life saving effect of aspirin in the second international study of infarct survival (ISIS-2) trial cannot be explained solely by prevention of late reocclusion of the infarct related artery. The aim of this study was to discover whether or not aspirin in combination with streptokinase had an adjuvant thrombolytic effect. DESIGN--Aspirin (150 mg) or placebo was given at the start of streptokinase infusion to 200 patients seen within six hours of the start of prolonged ischaemic cardiac pain and ST segment elevation. All patients received active aspirin at three hours. Patency of the infarct related artery was assessed non-invasively by the normalised rise of creatine kinase activity at three hours after starting streptokinase in these 200 patients and in a further 52 patients who had already taken aspirin within one week of the start of infarction. MAIN OUTCOME MEASURE--Rise in creatine kinase activity from baseline to > or = 20% or < 20% of the peak rise of activity in blood taken at three hours after starting infusion of streptokinase. This correlates with patency or occlusion of the infarct related coronary artery at about 2.5 hours after starting streptokinase. RESULTS--Assessed in this way, patency of the infarct related artery was 60% in patients given aspirin, 63% in those given placebo, and 62% in patients who had already taken aspirin within one week of infarction. CONCLUSION--The magnitude of the life saving effect of aspirin remains unexplained. Further investigation is needed into the mechanism of action of antiplatelet treatment in relation to thrombolytic treatment.