Use of bedside activated partial thromboplastin time monitor to adjust heparin dosing after thrombolysis for acute myocardial infarction: results of GUSTO-I. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries

Multiple five-day testing of rats in the open field and elevated plus-maze revealed a regressive dynamics of the integral characteristics of the exploratory behavior. The integral quantitative indices of searching activity in Henderson's test of extrapolation deliverance (modified by N. A. Bondarenko) and in active shock avoidance in N. R. Grigor'ev's problem box, on the contrary, displayed a progressive dynamics, like quantitative characteristics of cognitive activity. We established the differences between the determinants and control mechanisms of exploratory behavior and searching activity. This allowed us to differentiate these forms of behavior as different functional states.     

Cost-effectiveness of thrombolytic therapy for acute myocardial infarction

OBJECTIVE: To estimate the cost-effectiveness of thrombolytic therapy versus no thrombolytic therapy for patients following acute myocardial infarction, focusing on the impact of time to treatment on outcome. METHODS: A decision model was developed to assess the benefits, risks, and costs associated with thrombolytic therapy for treatment of acute myocardial infarction compared with standard nonthrombolytic therapy. The model used pooled data from a recent study of nine large randomized, controlled clinical trials and 12-month outcome data from a recently published meta-analysis of thrombolytic therapy trial data. Outcomes were expressed in terms of survival to hospital discharge and survival to 1 year after discharge. The risks of treatment that led to death, morbidity, or added costs were estimated. The model determined excess and marginal costs per death averted to hospital discharge and at 1 year. Results were also estimated in terms of cost per year of life saved. Sensitivity analyses included variations in time to treatment and drug cost. RESULTS: The marginal cost of thrombolytic therapy per death averted at 1 year was $222,344, or $14,438 per year of life saved. For patients treated within 6 hours of acute myocardial infarction, the marginal cost per death averted was $181,536 at 1 year, or $11,788 per year of life saved. CONCLUSIONS: Thrombolytic therapy is significantly more cost-effective than many other cardiovascular interventions and compares favorably with other forms of medical therapy. Results suggest that shortening the time to treatment has a critical impact on the cost-effectiveness of thrombolytic therapy.     

Significance of hemoptysis following thrombolytic therapy for acute myocardial infarction

PURPOSE: To describe the occurrence, cause, and significance of hemoptysis following thrombolytic therapy for acute myocardial infarction. PATIENTS AND METHODS: We retrospectively reviewed 2,634 patients presenting with acute myocardial infarction who received thrombolytic therapy to determine the incidence of hemoptysis. Chart and radiographic review included the type, dose, and route of thrombolytic therapy. In addition, the onset, duration, and severity of hemoptysis were recorded and correlated with radiographic and bronchoscopic findings. RESULTS: Eleven patients (0.4%) developed hemoptysis following administration of thrombolytic therapy for an acute myocardial infarction. The duration and severity had a wide range, although no patient had significant hemodynamic compromise. The source of hemoptysis was identified in only one patient who had a tongue laceration following cardiopulmonary resuscitation, and blood was seen within the oropharynx and trachea. No definitive cause was identified in all other patients. There was no correlation between the different types or doses of thrombolytic therapy and the duration or severity of hemoptysis. Chest radiographs were nonspecific and demonstrated resolution within 11 days following hemoptysis. CT of the thorax in one patient and bronchoscopy in two patients confirmed chest radiographic findings and in no patient was an underlying pulmonary abnormality identified. CONCLUSIONS: Pulmonary hemorrhage and hemoptysis are unusual complications of thrombolytic therapy in patients with acute myocardial infarction. Although hemoptysis may be the first indicator of an underlying pulmonary abnormality, we found no case in which a significant abnormality was unmasked. This study suggests that follow-up chest radiographs are recommended and further evaluation may be unnecessary if complete resolution is demonstrated.     

Diabetic retinopathy should not be a contraindication to thrombolytic therapy for acute myocardial infarction: review of ocular hemorrhage incidence and location in the GUSTO-I trial. Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries

OBJECTIVES: This study sought to evaluate the incidence of ocular hemorrhage in patients with and without diabetes after thrombolytic therapy for acute myocardial infarction. BACKGROUND: Ocular hemorrhage after thrombolysis has been reported rarely. However, there is concern that the risk is increased in patients with diabetes. In fact, diabetic hemorrhagic retinopathy has been identified as a contraindication to thrombolytic therapy without clear evidence that these patients have an increased risk for ocular hemorrhage. METHODS: We identified all suspected ocular hemorrhages from bleeding complications reported in patients enrolled in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-I trial. Additional information was collected on a one-page data form. We compared the incidence and location of ocular hemorrhages in patients with and without diabetes. RESULTS: There were 40,899 patients (99.7%) with information about diabetic history and ocular bleeding. Twelve patients (0.03%) had an ocular hemorrhage. Intraocular hemorrhage was confirmed in only one patient. There were 6,011 patients (15%) with diabetes, of whom only 1 had an ocular hemorrhage (eyelid hematoma after a documented fall). The upper 95% confidence intervals for the incidence of intraocular hemorrhage in patients with and without diabetes were 0.05% and 0.006%, respectively. CONCLUSIONS: Ocular hemorrhage and, more important, intraocular hemorrhage after thrombolytic therapy for acute myocardial infarction is extremely uncommon. The calculated upper 95% confidence interval for the incidence of intraocular hemorrhage in patients with diabetes was only 0.05%. We conclude that diabetic retinopathy should not be considered a contraindication to thrombolysis in patients with an acute myocardial infarction.     

Usefulness of ST-segment depression in non-infarct-related electrocardiographic leads in predicting prognosis after thrombolytic therapy for acute myocardial infarction

This study investigated both the in-hospital and long-term prognostic significance of ST-segment depression in non-infarct-related leads in patients who received thrombolytic therapy after acute myocardial infarction (AMI). We evaluated 221 consecutive patients who were admitted with their first AMI and underwent thrombolysis. Patients were followed for an average of 31 months and were classified into 3 groups: group 1 included 51 patients with persistent ST-segment depression, group 2 had 97 patients with transient ST-segment depression, and group 3 consisted of 73 patients without ST-segment depression (absent). Group 1 had significantly worse long-term survival during follow up by Kaplan-Meier analysis (55%) versus group 2 (81%) and group 3 (94%) (p = 0.0004) and higher event rates. This prognostic significance seemed to be maintained in both the anterior and inferior wall AMI groups. Multivariate analysis, using the Cox model, showed that Killip class, in-hospital left ventricular ejection fraction, and the persistence of ST-segment depression on the predischarge electrocardiogram (group 1) were independent predictors of survival. ST-segment depression in non-infarct-related leads on the predischarge electrocardiogram is an independent risk factor for worse long-term survival after anterior as well as inferior AMI treated with thrombolytic therapy.     

Beta-thromboglobulin plasma levels in the first week after myocardial infarction: influence of thrombolytic therapy

In vitro and in vivo studies have shown both an inhibition and an activation of platelets after thrombolysis in acute myocardial infarction. Plasma beta-thromboglobulin, a marker of platelet activity, was evaluated daily during the first week after myocardial infarction in 24 patients who received intravenous streptokinase (group 1) and 26 who did not (group 2). On admission, levels of beta-thromboglobulin, as compared to those in healthy subjects (35 +/- 9 IU/ml), were similarly augmented in group 1 (105 +/- 27 IU/ml) and in group 2 (115 +/- 30 IU/ml); 3 hours later, values averaged 191 +/- 58 IU/ml in group 1 (p < 0.001 vs baseline) and 95 +/- 28 IU/ml in group 2 (not significant vs baseline; p < 0.001 between the two groups). From the second to the seventh day, beta-thromboglobulin augmented in those patients in both groups with postinfarction angina. From day 5 to day 7, patients of group 1 without angina had lower beta-thromboglobulin levels than patients of group 2 who had no symptoms. The lowest levels of platelet activity were observed in group 1 reperfused patients. These data indicate that in myocardial infarction an early platelet activation takes place that is enhanced by thrombolytic treatment; recurrence of angina is associated with persistent activation; in the absence of recurrent angina, thrombolysis can limit late platelet activation.     

Prognostic significance of ST segment shift early after resolution of ST elevation in patients with myocardial infarction treated with thrombolytic therapy: the GUSTO-I ST Segment Monitoring Substudy

OBJECTIVES: We sought to study the relation between recurrent ST segment shift within 6 to 24 h of initial resolution of ST elevation after thrombolytic therapy and 30-day and 1-year mortality. BACKGROUND: Rapid and stable resolution of ST segment elevation in relation to thrombolytic therapy in patients with an acute myocardial infarction is an indicator of culprit artery patency. Whether recurrence of ST segment shift during continuous ST monitoring after initial resolution is related to poor prognosis has not been studied. METHODS: ST segment monitoring was performed within 30 min after thrombolytic therapy for acute myocardial infarction. The predictive value of a new ST segment shift (assessed as > or = 0.1-mV deviation from the baseline) 6 to 24 h after thrombolytic therapy was studied with respect to 30-day and 1-year mortality. RESULTS: Of 734 patients, 243 had a new ST segment shift (33%). The 30-day mortality rate in patients with an ST shift (7.8%) was significantly higher than that in patients without an ST shift (2.25%, p = 0.001), as was the 1-year mortality rate (10.3% vs. 5.7%, respectively, p = 0.025). Multivariable analysis revealed an independent predictive value of ST shift with respect to 30-day mortality (p = 0.008), even after consideration of multiple clinical risk factors in the overall Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO)-I mortality model (p = 0.0001). Moreover, the duration of the ST shift bore a direct relation with 1-year mortality (p = 0.008). CONCLUSIONS: Detection of ST segment shift early after thrombolytic therapy for acute myocardial infarction is a simple, noninvasive means of identifying patients at high risk and is superior to other commonly assessed clinical risk factors. Thus, patients with a new ST shift after the first 6 h, but within 24 h, represent a high risk group that may benefit from more aggressive intervention, whereas patients without evidence of an ST shift represent a low risk subgroup.     

Dipyridamole thallium-201 imaging very early after uncomplicated acute myocardial infarction in patients treated with thrombolytic therapy

The aim of this study was to assess the safety and prognostic value of dipyridamole 201T1 imaging very early after acute myocardial infarction in patients treated with thrombolytic therapy. Fifty-two consecutive patients with an uncomplicated clinical course underwent quantitative planar dipyridamole 201T1 imaging 2 5 days after acute myocardial infarction. The patients were followed for 14 +/- 7 months after discharge. No major complications occurred during the test. Of the 30 patients with redistribution, five (16.6%) developed in-hospital unstable angina as against none of the 22 patients without redistribution. During follow-up, a total of live late cardiac events were observed: two deaths and two cases of unstable angina in the group with reversible defects and one reinfarction in the group with fixed defects. The 1-year actuarial probability of being free of cardiac events was, respectively, 66 +/- 10% and 94 +/- 5% in the patients with and without redistribution (P < 0.01). In conclusion, in patients treated with thrombolysis, dipyridamole-201T1 imaging very early after uncomplicated acute myocardial infarction is a feasible and safe test. Patients with fixed defects appear to be at low risk and may be candidates for early discharge; the presence of redistribution identifies a subgroup of patients who may benefit from further careful clinical evaluation.     

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.     

ISIS 4: clinical controversy regarding magnesium infusion, thrombolytic therapy, and acute myocardial infarction

Magnesium (Mg) infusions over 24 hours were given to patients with suspected acute myocardial infarction (AMI) at least 2 hours after thrombolysis. Patients showed no benefit and even some increased risk in contrast to reduction in mortality obtained by Mg therapy in smaller trials. Results of all of the studies were pooled and statistically analyzed, according to a fixed-effects model that is inappropriate for studies of different protocols. The panel concluded that further study of Mg in AMI is not needed. This conclusion has been questioned.     

Diffuse pulmonary hemorrhage after fibrinolytic therapy for acute myocardial infarction

Occurrence of Non Hodgkin's lymphoma (NHL) in pregnancy is very rare. A 24-year-old woman with NHL stage IVB complicating pregnancy is presented. The diagnosis was made by biopsy at 27 weeks. The patient received combination chemotherapy which led to remission of the disease. The baby was delivered by an emergency caesarean section, due to fetal distress at 31 weeks. Unfortunately after a short period of remission a relapse occurred and magnetic resonance imaging (MRI) showed cerebral involvement, indicating a poor prognosis. She died seven months later from disseminated disease.     

Thrombolytic therapy for acute myocardial infarction

Numerous factors must be considered when determining the formulary status of thrombolytic agents for the treatment of acute myocardial infarction. Defined treatment options, predicted outcomes, and the economic consequences of this disorder continue to evolve from clinical trials. Pharmacists have a major role in delivering patient care, with responsibility for evaluating, procuring, and monitoring thrombolytic agents and drug therapy in general. By participating in the development and implementation of treatment guidelines, evaluating economic and therapeutic outcomes, providing timely optimal drug therapy, and educating health care providers and the public, they contribute significantly to the health care team.     

Myoglobin concentration in serum as an early marker of reperfusion in patients with acute myocardial infarction after thrombolytic therapy

Detection of coronary artery reperfusion in patients after thrombolytic therapy because of acute myocardial infarction includes, except angiography, disappearance of anginal pain, regression of electrocardiographic and echocardiographic myocardial ischaemia symptoms, increased activity of creatine kinase (CPK) and its isoenzyme CK-MB. The aim of the study was to check whether changes in myoglobin serum concentration could be an early marker of coronary artery reperfusion after thrombolysis in patients with acute myocardial infarction. The studies comprised 50 patients treated by thrombolysis due to threatening myocardial infarction, including 29 men and 21 women aged 43-84 years. The patients were divided into 2 groups: the first (i)-patients without symptoms of coronary artery reperfusion and the second (ii)-those with symptoms of coronary artery reperfusion. It was assumed that the basis for successful reperfusion would be the reduction of total elevations of the ST segment 70% or more in electrocardiographic recording performed 3 hours after the start of thrombolytic treatment. Reperfusion was considered completely unsuccessful when reduction of total elevations was less than 30%. In patients with reperfusion after thrombolysis the concentrations of myoglobin were much higher and the activity of CPK and CK-MB significantly more intensive in comparison with patients without reperfusion symptoms in electrocardiographic assay. The evaluation of myoglobin concentration, CPK and CK-MB activity in the 3rd hour after the start of thrombolytic treatment in relation to maximum values is characterised by high sensitivity and specificity in the prediction of reperfusion onset Maximum myoglobin concentration in serum appears significantly earlier than maximum CPK and CK-MB activity and this marker is characterised by higher sensitivity and specificity in the evaluation of coronary artery reperfusion than the activity of CPK and CK-MB.