Overview of randomized trials of intravenous heparin in patients with acute myocardial infarction treated with thrombolytic therapy

Intravenous heparin is routinely given after thrombolytic therapy for patients with acute myocardial infarction in the United States and in some, but by no means all, other countries. Several trials have documented improved infarct-artery patency in patients treated with heparin; however, none was large enough individually to assess the effect of heparin on clinical outcomes. We performed a systematic overview of the 6 randomized controlled trials (1,735 patients) to summarize the available data concerning the risks and benefits of intravenous heparin versus no heparin after thrombolytic therapy. Mortality before hospital discharge was 5.1% for patients allocated to intravenous heparin compared with 5.6% for controls (relative risk reduction of 9%, odds ratio 0.91, 95% confidence interval 0.59 to 1.39). Similar rates of recurrent ischemia and reinfarction were observed among those allocated to heparin therapy or control. The rates of total stroke, intracranial hemorrhage, and severe bleeding were similar in patients allocated to heparin; however, the risk of any severity of bleeding was significantly higher (22.7% vs 16.2%; odds ratio 1.55, 95% confidence interval 1.21 to 1.98). There was no significant difference in the observed effects of heparin between patients receiving tissue-type plasminogen activator and those receiving streptokinase or anisoylated plasminogen streptokinase activator complex, or between patients who did and did not receive aspirin. The findings of this overview demonstrate that insufficient clinical outcome data are available to support or to refute the routine use of intravenous heparin therapy after thrombolysis. It is not known if these findings are due to lack of statistical power, inappropriate levels of anticoagulation, or lack of benefit of intravenous heparin. Large randomized studies of heparin (and of new antithrombotic regimens) are needed to establish the role of such therapy.     

Streptokinase-induced activation of the kallikrein-kinin system and of the contact phase in patients with acute myocardial infarction

Thrombolytic therapy in acute myocardial infarction (AMI) is hampered by a considerable reocclusion rate. Thrombin activity is enhanced, and contact-system activation via plasminemia might be possible. Prospectively we examined the contact phase and the kallikrein-kinin system and additional molecular markers of hemostasis and fibrinolysis in AMI. In 22 patients with AMI, blood sampling was performed at admission and < or =10 days afterward. Eleven patients received 1.5 Mio U streptokinase (group A) and were compared with 11 AMI patients without thrombolytic therapy (group B). All patients had systemic heparinization (5,000 IU bolus, i.v.; 1,000 IU/h, i.v.). In group A (vs. group B), the kallikrein-factor XII system was significantly activated (3 h after start of therapy): kallikrein activity 140 +/- 41 (vs. 43 +/- 8) U/L (p < 0.05); kallikrein inhibition 87 +/- 9 (vs. 113 +/- 7%; p < 0.05), and factor XII 70 +/- 14 (vs. 94 +/- 6%). C1 inhibitor and factor XII inhibition were decreased. High-molecular-weight kininogen consumption indicating bradykinin generation was enhanced (p < 0.01). In group A, thrombin activity (TAT) was increased, and a hypercoagulative state with increased fibrin degradation products (d-dimer) was found. Plasmin activation in group A was reflected by decreased plasminogen and antiplasmin levels (p < 0.01). The findings indicate that streptokinase induces activation of the contact phase-kinin system in vivo associated with a consecutive increase of thrombin and bradykinin generation. Activation of this pathway might substantially contribute to reocclusion after initially successful thrombolytic therapy and to hypotensive reactions observed after streptokinase.     

Improvement in long-term prognosis of elderly patients with acute myocardial infarction after the introduction of intravenous thrombolytic therapy

Survival rate from a "thrombolytic" period of 351 patients above 66 years of age with acute myocardial infarction (AMI) was compared with that of 289 patients from a "prethrombolytic" period. The two groups were comparable regarding sex, age, previous AMI, cerebrovascular events, morbidity and mortality during admission. Survival rates after four years were 45.0% in the "thrombolytic" group and 38.4% in the "prethrombolytic" group (p = 0.047, log rank test). Using the Cox proportional hazard analysis, thrombolytic therapy was shown to be an independent prognostic predictor in "the thrombolytic population" with a relative risk of death from day 30 to end of follow-up of 0.4 (95% confidence interval 0.2-0.8). No interaction was found between age and thrombolysis. Although only one-fifth of the patients with AMI were eligible for thrombolysis, this treatment may have contributed to the improved long-term survival.     

In-hospital and follow-up mortality of patients with acute myocardial infarction

Patients with definite acute MI who were admitted to Songkla University Hospital between 1982 and 1990 were studied. The 195 patients and 202 admissions were nearly equally distributed between these 65 and older versus those younger than 65. Three quarters were males. The in-hospital mortality was 19.5 per cent and 76.3 per cent of the deaths were from heart failure. Neither age nor gender determined the mortality once corrected for the Killip's staging. There was no difference in mortality when comparing Q versus non-Q MI, anterior versus inferior wall MI or males versus females. One hundred and thirty-eight patients could be followed for and average of 27.1 months. First year mortality was 11 per cent and the first 2 years was 14 per cent. The in-hospital mortality, representing the prethrombolytic era, appeared to be similar to values reported from the Thai and Western literature. The predominance of death from heart failure rather than from arrhythmia may be a consequence of delayed admission whence arrhythmic death had already occurred or patients will seek hospital advice only if highly symptomatic.     

Withholding thrombolysis in patients with diabetes mellitus and acute myocardial infarction

The benefits of thrombolytic therapy in a patient with diabetes having a myocardial infarction are now well accepted but this treatment may be withheld inappropriately because of concerns about retinal haemorrhage. We therefore examined whether junior doctors alter their use of thrombolysis for the treatment of acute myocardial infarctions according to the type of diabetic retinopathy present. A questionnaire asking whether thrombolysis would be given to a 50-year-old male smoker with insulin-treated diabetes and an acute anterior MI was shown, with four unlabelled retinal photographs, to all doctors prescribing thrombolytic therapy in a south London teaching hospital and an affiliated district general hospital. In all, 24 medical SHOs, 16 medical registrars/specialist registrars, 3 medical senior registrars, and 23 casualty SHOs were interviewed. Of these 89% would thrombolyse such a patient with normal fundi, 55% with background diabetic retinopathy, 54 % if this also involved the macula, and 26% if they saw proliferative retinopathy. The more senior grades were more aggressive in their approach. As we believe that all patients with an acute anterior myocardial infarction and diabetes should be considered for thrombolysis irrespective of their retinal appearance these results suggest thrombolytic therapy is being withheld inappropriately.     

High-dose intravenous magnesium attenuates complement consumption after acute myocardial infarction treated by streptokinase

OBJECTIVE: This study was designed to detect changes in complement levels following acute myocardial infarction and to test whether magnesium sulphate (MgSO4) administration interferes with the complement response that follows acute myocardial infarction. DESIGN: Twenty-nine patients with acute myocardial infarction treated with streptokinase were included and randomly assigned to three treatment groups. In groups A and B, a bolus of 1 g MgSO4 was infused intravenously followed by 4 g (group A) and 14 g (group B) MgSO4 for 24 h while normal saline was administered in group C (control). Blood samples for C3, C4 and CH-100 were obtained at baseline and repeatedly during the 48 h following the initiation of magnesium infusion. RESULTS: In groups A and C, a remarkable decrease in the levels of C3, C4 and CH-100 was observed when measured 1 h after the end of streptokinase infusion and thereafter for the ensuing 48 h compared to baseline values (P < 0.05). In group B, the decrease in these complement elements was attenuated, and a significant (P < 0.05) delayed decrease of C3 and C4 was observed only at 24 h and later up to 48 h. The mean level of CH-100 in group B was significantly depressed compared to baseline from 3 h and thereafter up to 48 h. Mean C3 values plotted against observation time differed between the three groups (P = 0.021). A similar trend was observed for C4 (P = 0.133) but not for CH-100 (P = 0.46). CONCLUSION: (1) Complement elements are being consumed following acute myocardial infarction treated by streptokinase. (2) High-dose intravenous magnesium attenuates the complement process following acute myocardial infarction. (3) These results might signify that magnesium modulates the inflammatory response that follows infarction.     

Increase in jugular levels of polymorphonuclear neutrophil elastase in patients with acute cerebral infarction

To elucidate the involvement of activated polymorphonuclear neutrophil (PMN) proteolytic activity in the pathophysiology of cerebrovascular stroke, we measured internal jugular venous and femoral arterial levels of PMN elastase in 6 patients with acute stroke from the day onset (day 0) to 7 days after onset (day 7). Two patients with cerebral infarction demonstrated markedly elevated of PMN elastase in the jugular blood (730 and 1320 micrograms l-1, respectively), but not in the blood (203 and 205 micrograms l-1, respectively) on day 2. Both patients manifested signs of hemorrhagic infarction early on day 2. On day 4, the increased levels of jugular elastase returned to the normal range (< 250 micrograms l-1 in both patients. In contrast, none of the 4 patients with intracerebral hemorrhage demonstrated increased levels of PMN elastase in either the jugular or the arterial blood from days 0 to 7. The present study demonstrated a temporary but significant increase in jugular PMN elastase in patients with cerebral infarction, especially shortly after hemorrhagic infarction.     

Relation between ST-segment changes and myocardial perfusion evaluated by myocardial contrast echocardiography in patients with acute myocardial infarction treated with direct angioplasty

The aim of this study was to evaluate the relation between myocardial perfusion and ST-segment changes in patients with acute myocardial infarction treated with successful direct angioplasty. Thirty-seven patients, successfully treated with direct angioplasty, underwent myocardial contrast echocardiography before and after angioplasty. The sum of ST-segment elevation divided by the number of the leads involved (ST-segment elevation index) was calculated at 1, 5, 10, 20, and 30 minutes after restoration of a Thrombolysis In Myocardial Infarction trial grade 3 flow. After recanalization, myocardial reperfusion within the risk area was observed in 26 patients, whereas a no-reflow phenomenon occurred in 11. In patients with myocardial reperfusion, the ST-segment elevation index progressively declined, whereas in patients with no reflow, no significant change was observed. Reduction of > or = 50% in the ST-segment elevation index occurred in 20 of the 26 patients with reflow and in 1 of the 11 with no reflow (p = 0.0002). An additional increase of > or = 30% in the ST-segment elevation index occurred in 3 patients with reflow and in 7 with no reflow (p = 0.003). Sensitivity, specificity, positive and negative predictive values, and accuracy of the reduction in the ST-segment elevation index for predicting microvascular reflow were 77%, 91%, 95%, 62%, and 81%, respectively. The corresponding values of the increase in ST-segment elevation index for predicting no reflow were 64%, 88%, 70%, 85%, and 81%, respectively. In conclusion, after successful angioplasty, different patterns of myocardial perfusion are associated with different ST-segment changes. Analysis of ST-segment changes predicts the degree of myocardial reperfusion.     

Varying thrombolytic administration rates in elderly patients with acute myocardial infarction

Receipt of thrombolytic therapy in patients aged 75 or over with proven acute myocardial infarction admitted initially to either the coronary care unit (CCU) or a geriatric medical ward (GMW) was studied retrospectively in a hospital administering thrombolysis only in the CCU. Mean age and age distribution of patients admitted to each unit initially showed no significant difference. Of 50 patients admitted directly to the CCU, 28 (56%) received thrombolysis, compared with 13 of 50 (26%) GMW admissions (P < 0.02). Of 37 GMW admissions, 14 (38%) failed to receive thrombolysis without documented contraindication compared with 2 of 22 (9%) CCU admissions (P < 0.05). Aspirin was administered in 39 (78%) CCU and 31 (62%) GMW admissions (P < 0.05). Non-administration of aspirin without apparent contraindication occurred in 3 of 11 (27%) compared with 8 of 19 (42%) GMW admissions (NS). Elderly patients thus failed to receive thrombolytic therapy as a result of initial admission to a unit unable to administer this treatment.     

Randomized trial of direct coronary angioplasty versus intravenous streptokinase in acute myocardial infarction

OBJECTIVES: The objective of this study was to obtain preliminary data on the relative clinical utility of direct coronary angioplasty compared with that of intravenous thrombolytic therapy for patients with acute myocardial infarction. BACKGROUND: The relative merits of intravenous thrombolytic therapy and direct coronary angioplasty as treatment for acute myocardial infarction are incompletely understood, and randomized trials of these treatments have been extremely limited. METHODS: One hundred patients with ST segment elevation presenting to a single high volume interventional center within 6 h of the onset of chest pain were randomized to receive either streptokinase (1.2 million U intravenously over 1 h) or immediate catheterization and direct coronary angioplasty. Patients were excluded for age > or = 75 years, prior bypass surgery, Q wave infarction in the region of ischemia or excessive risk of bleeding. All patients were then treated with aspirin (325 mg orally/day) and heparin (1,000 U intravenously/h) for 48 h until catheterization was performed to determine the primary study end point, namely, infarct-related artery patency at 48 h. Secondary end points were in-hospital death, left ventricular ejection fraction at 48 h and time to treatment. RESULTS: There was no difference in the baseline characteristics of the two treatment groups. Overall patient age was 56 +/- 10 years, 83% of patients were male, 11% had prior infarction, 40% had anterior infarction and 97% were in Killip class I or II. Although time to treatment was delayed in the angioplasty group (238 +/- 112 vs. 179 +/- 98 min, p = 0.005), there was no difference in 48-h infarct-related artery patency or left ventricular ejection fraction (patency 74% vs. 80%; ejection fraction 59 +/- 13% vs. 57 +/- 13%; angioplasty vs. streptokinase, p = NS for both). There were no major bleeding events, and the mortality rate with angioplasty (6%) and streptokinase (2%) did not differ (p = NS). CONCLUSIONS: These results suggest that intravenous thrombolytic therapy might be preferred over coronary angioplasty for most patients because of the often shorter time to treatment.     

太极拳锻练对急性心肌梗塞患者的康复作用

目的:探讨长期太极拳锻练对急性心肌梗塞患者的康复作用.方法:将符合入选标准的心肌梗塞患者132例,随机分为对照组(66例)和太极拳锻练康复组(康复组,66例),对照组给予标准心肌梗塞常规药物治疗,康复组在常规药物治疗的基础上进行太极拳康复锻练,为期一年.两组患者于入组时及观察/康复一年期满时分别测试生活质量评分、6min步行距离(6MWT)、左室射血分数(LVEF),并对两组患者在试验期间的心律失常发生率、心绞痛发生率、心肌再梗塞发生率进行了比较.结果:与对照组比较,康复组在生活质量、6min步行距离、左室射血分数方面均有明显提高(P＜0.01),而心律失常发生率、心绞痛发生率、心肌梗塞再发生率明显低于对照组(P＜0.05).结论:太极拳锻练能有效改善心功能,改善心肌代谢,促进心肌梗塞患者的康复.     

Clinical implications of left ventricular function in patients with acute myocardial infarction

Correlation of left ventricular filling pressure (55 patients) with the left ventricular stroke work index (61 patients) provided a rapid means of objectively determining ventricular performance after myocardial infarction. Pressure was monitored by means of the Swan-Ganz balloon-tipped catheter and thermal indicators were used for measuring cardiac output. A hemodynamic grouping of these myocardial infarction patients on the basis of the stroke work index showed close correlation with morbidity and mortality and provided a more accurate prognostic indicator than did the commonly used clinical predictors. Serial assessment of ventricular function further aided in defining the prognosis when it was not clear on admission. Thus, the levels of normal or abnormal ventricular function and the effect of therapeutic measures can be rapidly evaluated by determining the pressures and flows in patients with acute myocardial infarction.     

Emergency department use of aspirin in patients with possible acute myocardial infarction

OBJECTIVE: To determine the relevance of the functional affinity of IgM rheumatoid factor (RF) to the clinical and serological characteristics of patients with rheumatoid arthritis. METHODS: The functional affinity of IgM RF of 57 seropositive rheumatoid arthritis patients was evaluated by an enzyme linked immunosorbent assay based on the use of a chaotropic agent. The inhibition index was taken as an estimate of functional affinity. The patient group was divided into high functional affinity subgroup 1 (functional affinity < 0.5, n = 37) and low functional affinity subgroup 2 (functional affinity > 0.5, n = 20). The medical records of all patients were reviewed with a particular note of the disease activity and the articular damage score. RESULTS: The disease duration was shorter (P < 0.01) in subgroup 1 patients [7.9 (SD 6.4) years] than in subgroup 2 patients [13.4 (11.29) years], so that Ritchie's, Lee's, and Steinbrocker's indices were lower in the former than in the latter (P < 0.01, 0.001, and 0.01, respectively). In contrast, erythrocyte sedimentation rates, C reactive protein concentrations, antinuclear antibody, and HLA DR4 prevalences were similar in the two subgroups. CONCLUSIONS: Different forms of RF are present during progression of the disease.     

Delay and hospitalisation with acute myocardial infarction

We examined patient behaviour and the components of delay to hospitalisation in 149 consecutive cases of proven acute myocardial infarction (AMI) prospectively. The median total delay from onset of chest pain to hospitalisation was 210 mns (range 5 mns to 7 days). The median delay before seeking medical help was 105 mns. Seventy-eight patients (52%) contacted a G.P. Median delay to G.P. contact was 15 mns. The median delay in transportation to hospital was 20 mns. There was no evident diurnal variation in the onset of symptoms. There was no significant differences in help seeking delay between the sexes, between young and old or between those with a previous history of ischaemic heart disease similar to studies in the U.S. and U.K. Patient delay to seeking help remains the major and most crucial component of delay in treating AMI.     

Clinical and angiographic features of patients with an occluded versus a patent infarct vessel after intravenous streptokinase for acute myocardial infarction

Despite early treatment with thrombolytic agents for acute myocardial infarction, a significant portion of patients fail to achieve a patent infarct artery. To study the various factors related to achieving patency in the infarct vessel, 201 patients who received streptokinase within six hours of symptoms were studied. All patients underwent cardiac catheterization during the same hospitalization at 5.40 +/- 3.26 days after admission. Forty-five (22.4%) patients were found to have an occluded infarct artery (group 1) and 156 (77.6%) had a patent infarct vessel (group 2). There was no difference in the time from onset of symptoms to receiving streptokinase between the two groups. The two groups were similar to each other with regard to age, gender, history of myocardial infarction or angina, and major risk factors for coronary disease. Coagulation parameters before and after streptokinase therapy, reflecting the lytic state, were similar in both groups. The left ventricular end diastolic pressure was significantly higher and the left ventricular ejection fraction was significantly lower in group 1 than in group 2. These observations suggest that despite early initiation of thrombolytic therapy in patients with acute myocardial infarction, a significant portion of patients fail to achieve a patent infarct artery. This failure cannot be explained by the observed clinical parameters or the lytic state after streptokinase.     

Ultrasonic tissue characterization in predicting residual ischemia and myocardial viability for patients with acute myocardial infarction

The identification of viable myocardium and residual ischemia in patients with acute myocardial infarction has important prognostic implications. The ultrasonic tissue characterization with integrated backscatter and dobutamine-atropine stress echocardiography were performed 8.3+/-3 days after AMI in 30 patients. After coronary angioplasty for the residual stenosis of infarct-related artery, both modalities were repeated. The parameter obtained from ultrasonic tissue characterization, phase-weighted variation, could differentiate the myocardium with residual coronary stenosis or nonviable myocardium from the viable myocardium without residual coronary stenosis (p < 0.001). Using the cutoff value of 5.8 dB, the sensitivity, specificity and accuracy for detecting viable myocardium without residual coronary stenosis were 75%, 100% and 90.2%, respectively. The phase-weighted variation of the viable infarction zone restored after the coronary stenosis was relieved. In contrast, the nonviable myocardium had a small phase-weighted variation that was irrelevant to the patency of the infarct-related artery. The ultrasonic tissue characterization may be used in identifying patients with acute myocardial infarction whose infarction zones are viable without residual ischemia.     

Haemodynamic and electrocardiographic effects of intravenous disopyramide (rythmodan) following acute myocardial infarction

1 The haemodynamic and electrocardiographic effects of intravenous disopyramide were studied in fifteen patients with acute myocardial infarction. 2 Five minutes after drug injection a rise in heart rate, aortic mean and diastolic pressures and systemic vascular resistence was noted which persisted for at least 30 min. A small increase in pulmonary arterial diastolic pressure (mean = 1.5 mm Hg) occurred at 5 min only and no significant change of cardiac output was found throughout the period of the study (1 h). 3 Surface electrocardiograms revealed transient prolongation of the P-R interval and a sustained increase in the QTc interval. 4 The haemodynamic changes suggest an anticholinergic effect of the drug. There was no definite evidence of a negative inotropic effect in this study, however, these peripheral haemodynamic measurements might not have revealed a modest negative inotropic effect. 5 The electrocardiographic changes are similar to those previously reported in normals and in patients without acute myocardial infarction.     

Determinants of decisions to seek medical treatment by patients with acute myocardial infarction symptoms.

Among 43 myocardial infarction patients (mean age 53.4 yrs), Ss who delayed between noting initial symptoms and deciding they were ill were those who reported that they characteristically exhibited some Type A behaviors, experienced little initial pain at a time when work was quite demanding, responded to their symptoms with depression and fatigue, and were currently quite pessimistic about their health. Those who delayed between deciding they were ill and seeking treatment were those who were assessed as Type B on the structured interview and who talked to others to assess the meaning of their symptoms. (38 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)