Long-term benefit of early thrombolytic therapy in patients with acute myocardial infarction: 5 year follow-up of a trial conducted by the Interuniversity Cardiology Institute of The Netherlands

Patients (n = 533) who participated in the Interuniversity Cardiology Institute of the Netherlands Trial were followed up for 3 to 7 years. The 5 year survival rate after thrombolytic therapy with intracoronary streptokinase was 81% (269 patients) compared with 71% after conventional therapy (264 patients). The greatest improvement in survival was observed in patients with anterior infarction (81% versus 64% with thrombolytic therapy or conventional therapy, respectively), in those with heart failure on admission or a previous infarction and in those with extensive myocardial ischemia on admission. Left ventricular ejection fraction at the time of hospital discharge was better after thrombolytic therapy. In the hospital survivors, long-term outcome was related to left ventricular function at the time of discharge and, to a lesser extent, to the underlying coronary artery disease. The initial therapy (thrombolysis or conventional) was not an independent additional determinant of long-term survival when left ventricular function and coronary status at the time of hospital discharge were taken into account. Thus, the salutary effects of thrombolytic therapy appear to be the result of myocardial salvage. Reinfarction within 3 years was observed more frequently after thrombolytic therapy, particularly in patients with inferior wall infarction and those with greater than or equal to 90% stenosis of the infarct-related vessel at discharge. Coronary bypass surgery and coronary angioplasty were performed more frequently after thrombolytic therapy than in conventionally treated patients. At 5 years, approximately 40% of patients in both groups had an uneventful course without reinfarction or additional revascularization procedures. These observations demonstrate that the benefits of thrombolytic therapy are maintained throughout 5 years of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cost benefit analysis of early thrombolytic treatment with intracoronary streptokinase. Twelve month follow up report of the randomised multicentre trial conducted by the Interuniversity Cardiology Institute of The Netherlands.

The costs and benefits of early thrombolytic treatment with intracoronary streptokinase in acute myocardial infarction were compared in a randomised trial. All hospital admissions were recorded and the functional class was assessed at visits to the outpatient clinic during a 12 month follow up of 269 patients allocated to thrombolytic treatment and of 264 allocated to conventional treatment. Mean survival during the first year was calculated for patients with inferior and with anterior infarction and adjusted for impaired quality of life in cases where there were symptoms or hospital admission. In patients with inferior infarction mean survival was 337 days (out of a total follow up of 365 days) for patients allocated to thrombolytic treatment and 327 days for controls. Quality adjusted survival was seven days longer in the thrombolysis group (307 vs 300 days in controls). In patients with anterior infarction mean survival was significantly longer (35 days) in the thrombolysis group than in the control group as was quality adjusted survival (38 days) (304 vs 266 days in controls). The gain in life expectancy with thrombolytic treatment was 0.7 years for patients with inferior infarction, 2.4 years for patients with anterior infarction, and 3.6 years for the subset of patients with large anterior infarction who were admitted within two hours of the onset of symptoms. The costs of medical treatment, including medication, hospital stay, cardiac catheterisation, coronary angioplasty, and bypass surgery, in the first year follow up were higher inpatients allocated to thrombolytic treatment (an additional cost ofDfl 7000 in inferior and Dfl 9000in anterior infarction (1 pounds sterling approximately Dfl 3.3.)) than in conventionally treated patients. The additional costs per year of life gained were Dfl 10 000 in inferior infarction, Dfl 3 800 in anterior infarction, and only Dfl 1 900 in patients with large anterior infarction admitted within two hours of onset of symptoms.Intracoronary thrombolysis can be recommended as a cost effective treatment in patients with extensive anteroseptal infarction.     

Cost benefit analysis of early thrombolytic treatment with intracoronary streptokinase. Twelve month follow up report of the randomised multicentre trial conducted by the Interuniversity Cardiology Institute of The Netherlands

The costs and benefits of early thrombolytic treatment with intracoronary streptokinase in acute myocardial infarction were compared in a randomised trial. All hospital admissions were recorded and the functional class was assessed at visits to the outpatient clinic during a 12 month follow up of 269 patients allocated to thrombolytic treatment and of 264 allocated to conventional treatment. Mean survival during the first year was calculated for patients with inferior and with anterior infarction and adjusted for impaired quality of life in cases where there were symptoms or hospital admission. In patients with inferior infarction mean survival was 337 days (out of a total follow up of 365 days) for patients allocated to thrombolytic treatment and 327 days for controls. Quality adjusted survival was seven days longer in the thrombolysis group (307 vs 300 days in controls). In patients with anterior infarction mean survival was significantly longer (35 days) in the thrombolysis group than in the control group as was quality adjusted survival (38 days) (304 vs 266 days in controls). The gain in life expectancy with thrombolytic treatment was 0.7 years for patients with inferior infarction, 2.4 years for patients with anterior infarction, and 3.6 years for the subset of patients with large anterior infarction who were admitted within two hours of the onset of symptoms. The costs of medical treatment, including medication, hospital stay, cardiac catheterisation, coronary angioplasty, and bypass surgery, in the first year follow up were higher inpatients allocated to thrombolytic treatment (an additional cost ofDfl 7000 in inferior and Dfl 9000in anterior infarction (1 pounds sterling approximately Dfl 3.3.)) than in conventionally treated patients. The additional costs per year of life gained were Dfl 10 000 in inferior infarction, Dfl 3 800 in anterior infarction, and only Dfl 1 900 in patients with large anterior infarction admitted within two hours of onset of symptoms.Intracoronary thrombolysis can be recommended as a cost effective treatment in patients with extensive anteroseptal infarction.     

Usefulness of the presenting electrocardiogram in predicting myocardial salvage with thrombolytic therapy in patients with a first acute myocardial infarction.

AIMS: Patients with Q waves and T-wave inversion are generally at a later stage of the infarction process than patients without these changes. Our aim was to investigate whether a single assessment of electrocardiographic parameters at presentation would predict the proportion of myocardium salvageable by thrombolytic therapy. METHODS AND RESULTS: Electrocardiographic algorithms to calculate the potential and final infarct size have been developed and allow the proportion of myocardium salvageable with therapy to be calculated. This was measured in 146 patients with acute myocardial infarction who had angiography at a median of 91 min after streptokinase. The relationship between myocardial salvage and the electrocardiographic parameters at presentation (Q waves, T-wave inversion, quantitative ST segment changes, and the initial QRS score), was examined together with the 90-min angiographic parameters (TIMI flow grade and collateral grade), clinical parameters (haemodynamics and age), and time to therapy. Parameters that correlated with myocardial salvage included the initial QRS score (r=-0.56, P<0.0001), Q wave grade (r=-0.36, P<0.0001), number of leads with ST depression (r=0.28, P<0.001), maximum ST depression (r=0.27, P<0.01), T-inversion grade (r=-0.26, P<0.01), and TIMI flow grade at 90 min (r=0.21, P<0.02). The time from symptom onset to thrombolytic therapy did not correlate with salvage (r=-0.09). On multivariate analysis, only the initial QRS score and T-inversion grade on the initial electrocardiogram were independent predictors of salvage (multivariate r using both variables combined=0.57, P<0.001). CONCLUSIONS: The QRS score and T-wave inversion grade on the presenting electrocardiogram provide important information in predicting myocardial salvage. These parameters may help triage patients to appropriate therapies.     

Intracoronary thrombolytic therapy in acute myocardial infarction: a prospective, randomized, controlled trial

A prospective, randomized trial was designed to assess the efficacy of intracoronary thrombolytic therapy with streptokinase (STK) in acute myocardial infarction. Sixty-four patients with acute myocardial infarction were randomized within 6 hours of onset of symptoms to 1 of 3 groups. Sixteen patients were treated by conventional means (control group). Nineteen patients underwent coronary arteriography and received corticosteroids and intracoronary and intravenous nitroglycerin (NTG group). Twenty-nine patients received management identical to that of the NTG group, with the addition of intracoronary STK therapy (STK group). Recanalization was demonstrated in 21 of 29 patients (72%) in the STK group. Global and regional ejection fraction (EF) was determined by radionuclide ventriculography before any intervention and 7 to 10 days later. No significant improvement in global EF was achieved in the control and NTG groups. In STK patients as a group, global EF did not increase significantly; however, in patients recanalized with STK, EF improved from 42 +/- 17% to 49 +/- 16% (p = 0.023). All groups showed wide variability of response. Improvement in global EF of more than 5% was noted in 44% of patients recanalized with STK. When subgrouped on the basis of initial global EF of 45% or less or more than 45%, only patients recanalized with STK with an initial EF of 45% or less had an improved global EF (from 30 +/- 10% to 42 +/- 10%, p = 0.015).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of thrombolytic therapy on the high-resolution electrocardiogram after myocardial infarction.

The effects of thrombolytic treatment was studied in 109 consecutive patients 9-11 days after their first acute myocardial infarction by high-resolution electrocardiography (ECG), 24 h Holter monitoring, exercise test and radionuclide ventriculography. Thirty-seven patients were treated with intravenous thrombolytic agents. Thrombolytic treatment was assessed by clinical criteria to be successful in 22 patients and probably successful in 12 patients. Thrombolysis failed in three patients and 72 patients did not receive thrombolytic treatment (control group). Measurements made on the high-resolution and filtered (60 Hz high-pass) vectormagnitude complex included the total duration, the duration of the potential less than 40 microV, the root mean square (RMS) voltage in 10 ms intervals over the first 50 ms and RMS voltage of the last 40, 50 and 60 ms. The filtered QRS duration was significantly shorter in reperfused patients compared with the control group (83 +/- 10 vs 89 +/- 12 ms; P = 0.017). In inferior infarcts (n = 57) the filtered QRS duration was 83 +/- 11 ms in reperfused and 89 +/- 10 ms in non-reperfused patients (P = 0.044), but in anterior infarcts (n = 52) there was no difference. The RMS voltage of the initial 50 ms of the QRS was higher in the reperfused than in non-reperfused anteroseptal infarcts (38 +/- 14 v 23 +/- 10 microV; P = 0.022). Patients successfully treated with thrombolytic agents within the first 2 h had higher RMS voltage of the terminal 40 ms of the QRS than patients treated within 2-4 h (38 +/- 17 vs 27 +/- 17 microV; P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)     

东菱克栓酶冠状动脉溶栓治疗急性心肌梗塞的临床研究

报告6例发病时间在4～10小时内的急性心肌梗塞患者，采用冠状动脉狭窄口堵塞近端注入东菱克栓酶（DF－521）20～30BU（Batroxobinunit简称BU，是Batroxobin的酶活性量的表示单位。37℃以下，标准人～枸椽酸血浆0．3ml中加入Batroxobin溶液0．1ml，19．0±0．2秒发生凝固时其酶活性为2BU）。进行溶栓治疗，60～90分钟后重复冠状动脉造影。结果全部有效，4例闭塞管腔再通（TIMI达Ⅲ级）2例大部分再通（TIMI达Ⅱ级），从而限制了梗塞发展且无出血及其它并发症，效果显著，值得进一步研究推广。     

The electrocardiogram and thrombolytic therapy in patients with acute myocardial infarct

The objective of the submitted work is to analyze in patients with acute myocardial infarction (AIM) local priority data on ECG markers after admission to hospital, data on some associations of ECG and thrombolytic treatment and to assess in patients with the first AMI data on hospital mortality in connection with some ECG markers. The project was implemented as a prospective multicentre study. An independent audit and collection of data was done in 3123 patients with AIM in 66 departments between Sept. 16 1997 and Sept. 15 1998. The group included patients admitted within 96 hours after development of complaints with the diagnosis or suspicion of AMI who were discharged with the diagnosis of a first/repeated AMI. Elevation of ST segments was recorded in 67.1%, a Q wave in 42.2% and left bundle branch block in 3.7% of the patients. Early diagnosis of AMI based on ECG and data on prolonged stenocardia was made in 55.6% patients. This is the maximal proportion of patients where thrombolytic treatment can be contemplated. Thrombolytic treatment was not administered to 54.9% patients with elevations of the ST segments and in as many as 81.2% patients with left bundle branch block. The hospital mortality in patients with a first AMI is significantly greater in patients with elevations of the ST segment, Q infarction, anterior wall infarction, combined infarction, right ventricular infarction and in patients with bundle branch and fascicular block. It was confirmed that in Slovakia in clinical practice thrombolytic treatment is not always administered consistent with criteria adopted from randomized studies. The result is underutilization or overutilization of thrombolytic treatment to patients with AIM in clinical practice. Underutilization of thrombolytic treatment is generally known. It was demonstrated that attention must be devoted also to overutilization of thrombolytic treatment. All patients where significantly higher hospital mortality was recorded must receive special care already on admission to hospital.     

Value and limitations of thrombolytic therapy in early acute transmural myocardial infarction

Since coronary thrombosis is the final common pathway by which acute transmural myocardial infarction occurs, intracoronary thrombolytic reperfusion has taken on new significance. The goals of early restoration of coronary blood flow are to reduce mortality as well as to demonstrate improvement of markers of success or failure associated with thrombolytic therapy relative to nonreperfused patients. This paper examines clinical studies from multiple centers and the results derived from these studies. Mortality, left ventricular function, electrocardiographic indices of necrosis, laboratory studies, enzymatic indices of myocardial infarction size, thallium perfusion, and scintigraphic studies from controlled randomized and nonrandomized studies are presented. Overall, it appears that thrombolytic reperfusion is beneficial if applied early, although the markers of success or failure do not necessarily correlate with short-term mortality.     

心电图在判定急性下壁心肌梗死犯罪血管

目的评定心电图在判定急性下壁心肌梗死罪犯血管的意义。方法对５６例急性下壁心肌梗死患的心电图及冠状动脉造影资料进行分析。结果①罪犯血管是右冠状动脉占８５．７％,回旋支占１４．３％;②窦性心动过缓、房室传导阻滞、室颤是右冠状动脉闭塞指标;③ＳＴＩ．ａＶＬ压低≥１．０ｍｍ是右冠状动脉闭塞敏感指标（Ｐ＜０．０５及Ｐ＜０．０１）,敏感性及特异性分别为６９％、７５％及９２％、７５％,而缺乏ＳＴＩ．ａＶＬ压低     

Clinical benefits of thrombolytic therapy in acute myocardial infarction.

The value of coronary artery reperfusion resulting from pharmacologically induced fibrinolysis in patients with evolving myocardial infarction has been rigorously evaluated. Improved left ventricular function and even more impressive improvements in survival rates have been demonstrated consistently in controlled studies. Benefit is related to the restoration of myocardial blood flow. Maximal benefit is achieved with early and sustained restoration of coronary artery patency. Benefits observed during initial hospitalization are sustained for at least 1 year in the majority of patients, even without subsequent mechanical revascularization. To date, analysis of subgroups has not identified a population of patients with evolving infarction that should routinely be excluded from consideration for thrombolysis. As with many potent pharmacologic agents, activators of the fibrinolytic system are associated with a degree of risk whenever they are administered to a patient. Therefore, patients must be assessed carefully prior to initiating treatment, especially for potential bleeding hazards, and appropriate follow-up evaluation and concomitant therapy needs to be planned. However, given the overwhelming body of data now available regarding its benefits and relative safety, thrombolysis should be considered as conventional therapy for patients with acute evolving myocardial infarction (AMI).     

急性心肌梗死的药物溶栓治疗进展

早期溶栓治疗 (ｔｈｒｏｍｂｏｌｙｔｉｃｔｈｅｒａｐｙ ,ＴＴ)可获得梗塞相关动脉 (ＩＲＡ)早期开放 ,有效缩小心肌梗死面积 ,保护左室功能 ,降低病死率 ,因而成为急性心肌梗死(ＡＭＩ)的常规疗法之一。然而 ,目前最佳的溶栓方案仅能使 5 4%的ＡＭＩ获得充分再灌注 ,溶栓后血管再闭塞率为 8 0 %～13 5 % ,出血并发症仍存在 ,尤其颅内出血为 0 3 %～ 1%。如何提高溶栓疗效、降低副反应仍是当前倍受关注的课题。现将这方面的一些进展综述如下。1　溶栓适应证在扩大　　溶栓病例选择在 1996年中华心血管病杂志编委会制定的参考方案基础上有…     

Determinants of prognosis in symptomatic ventricular tachycardia or ventricular fibrillation late after myocardial infarction. The Dutch Ventricular Tachycardia Study Group of the Interuniversity Cardiology Institute of The Netherlands

In a multicenter study, 390 patients with sustained symptomatic ventricular tachycardia or ventricular fibrillation late after acute myocardial infarction were prospectively followed up to assess determinants of mortality and recurrence of arrhythmic events. Patients were given standard antiarrhythmic treatment, which consisted primarily of drug therapy. During a mean follow-up period of 1.9 years, 133 patients (34%) died; arrhythmic events and heart failure were the most common cause of death (41 patients [11%] died suddenly, 31 [8%] died because of recurrent ventricular tachycardia or ventricular fibrillation and 23 [6%] died of heart failure). One hundred ninety-two patients (49%) had at least one recurrent arrhythmic event; 85% of first recurrent arrhythmic events were nonfatal. Multivariate analysis of data from patients who developed the arrhythmia less than 6 weeks after infarction identified five variables as independent determinants of total mortality: 1) age greater than 70 years (risk ratio 4.5); 2) Killip class III or IV in the subacute phase of infarction (risk ratio 3.5); 3) cardiac arrest during the index arrhythmia (risk ratio 1.7); 4) anterior infarction (risk ratio 2.2); and 5) multiple previous infarctions (risk ratio 1.6). Multivariate analysis of data from patients developing the arrhythmia greater than 6 weeks after infarction identified four variables as independently predictive of total mortality: 1) Q wave infarction (risk ratio 2.1); 2) cardiac arrest during the index arrhythmia (risk ratio 1.7); 3) Killip class III or IV in the subacute phase of infarction (risk ratio 1.7); and 4) multiple previous infarctions (risk ratio 1.4). The results of the two multivariate analyses were used in a model for prediction of mortality at 1 year. The average predicted mortality rate varied considerably according to the model: for 243 patients (62%) with the lowest risk, it was 13%, corresponding to an observed mortality rate of 12%; for 92 patients (24%) with intermediate risk, it was 27%, corresponding to an observed rate of 28%; for 55 patients (14%) with the highest risk, it was 64%, corresponding to an observed rate of 54%. This study shows that patients with symptomatic ventricular tachycardia or ventricular fibrillation late after myocardial infarction who are given standard antiarrhythmic treatment have a high mortality rate. The predictive model presented identifies patients at low, intermediate and high risk of death and can be of help in designing the appropriate diagnostic and therapeutic strategy for the individual patient.     

A cost-effectiveness model of thrombolytic therapy for acute myocardial infarction

OBJECTIVE: To assess the short- and long-term costs and clinical and quality of life outcomes with the use of streptokinase (SK) vs tissue plasminogen activator (tPA) for acute myocardial infarction (MI). DESIGN: A decision analysis model. PATIENTS: Patients with acute MI who were candidates for thrombolytic therapy and who presented within six hours of symptom onset. MEASUREMENTS: 30-day and one-year mortality, impacts of disabling and nondisabling stroke, reinfarction, hemorrhage, hypotension, anaphylazis, and long-term medical costs. RESULTS: Using 30-day mortality data from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial, the baseline analysis yielded an incremental cost—effectiveness for tPA of $30,300 per additional quality-adjusted life year (QALY) gained, compared with SK. Using one-year mortality data from the GUSTO trial, the analysis yielded an incremental cost—effectiveness for tPA of $27,400 per additional QALY, compared with SK. The incremental cost—effectiveness of tPA over SK was sensitive to the difference in mortality seen with the two agents, exceeding $100,000 per QALY, for a relative survival advantage of approximately one-third that seen in the GUSTO trial. The incremental cost per QALY of tPA remained under $60,000 if the survival benefit was half that seen in the GUSTO trial. The cost—effectiveness of tPA declined with a shorter projected life expectancy following MI and for inferior (vs anterior) wall infarction. The analysis was modestly sensitive to the costs of the thrombolytic agents. CONCLUSIONS: In spite of its higher cost relative to SK, tPA is a cost-effective therapy for MI under a wide range of assumptions regarding clinical outcomes and costs. Presented in part at the Congress of the European Society of Cardiology, August 29–September 2, 1993, Nice, France. Supported by a research grant from Kabi Pharmacia. Dr. Kalish is the recipient of a Merck/American Federation for Aging Research Fellowship in Clinical Geriatric Pharmacology. Dr. Gurwitz is the recipient of a Clinical Investigator Award (K08 AG00510) from the National Institute on Aging, Bethesda, Maryland.     

急性心肌梗死时体表心电图对梗死相关动脉的判断

目的了解急性心肌梗死(AMI)的体表心电图对心肌梗死相关动脉(IRA)及其闭塞位置判断作用.方法对264例急性心肌梗死患者的心电图和冠状动脉造影资料进行回顾性对比分析.结果①下壁AMI时血管闭塞发生在右冠状动脉(RCA)74例(78.7%),左回旋支(LCX)20例(21.3%).Ⅰ、aVL导联ST段压低提示RCA为IRA的敏感性,特异性和阳性预测值分别为94.6%,70%和92.1%.ST段压低Ⅰ＜aVL提示RCA为IRA的敏感性,特异性和阳性预测值分别为83.8%,90%和96.9%.ST段抬高Ⅱ＜Ⅲ提示RCA为IRA的敏感性,特异性和阳性预测值分别为90.5%,90%和97.1%.ST段压低Ⅰ＜aVL和ST段抬高Ⅱ＜Ⅲ提示RCA为IRA的敏感性,特异性和阳性预测值分别为81.8%,100%和100%.非ST段压低Ⅰ＜aVL和非ST段抬高Ⅱ＜Ⅲ提示LCX为IRA的敏感性,特异性和阳性预测值分别为85%,100%和100%.13例合并右室心梗IRA均为RCA.②前间壁AMI时STⅠ、STaVL抬高,STⅡ、Ⅲ、aVF下降均不能提示IRA为LAD或RCA(P分别大于0.05).③前壁AMI时STⅠ、STaVL抬高,STⅡ、Ⅲ、aVF下降判断LAD近段闭塞的敏感性、特异性和阳性预测值分别为70.4%,59.3%,87%,95.7%和86.4%,94.1%.④广泛前壁AMI时STⅠ、STaVL抬高,STⅡ、Ⅲ、aVF下降判断LAD近段闭塞的敏感性、特异性和阳性预测值分别为100%,95.5%,85.7%,100%和97.8%,100%.结论下壁、前壁和广泛前壁AMI时体表心电图对心肌梗死相关动脉(IRA)及其闭塞位置判断具有预测价值.     

Clinical controversies surrounding thrombolytic therapy in acute myocardial infarction

The treatment of acute myocardial infarction has changed tremendously in the past decade because thrombolytic therapy has become the treatment of choice for the patient with acute myocardial infarction. Although many issues have been resolved, several controversial issues remain unresolved. This article addresses thrombolytic agents in terms of their superiority in achieving infarct vessel patency and mortality reduction as well as the role of thrombolysis in patients who present with chest pain of greater than 6 hours' duration, who are elderly, and who have an inferior infarction.