Cardiac tamponade early after thrombolysis for acute myocardial infarction: a rare but not reported hemorrhagic complication.

Among 392 consecutive patients admitted for acute myocardial infarction and treated with thrombolytic drugs, 4 patients (1%) developed an early hemorrhagic pericardial effusion (without ventricular wall rupture) evolving within 24 h to cardiogenic shock consequent to cardiac tamponade. They all suffered from a large anterior myocardial infarction treated within 4 h after onset of symptoms with intravenous anisoylated plasminogen streptokinase activator complex (one case), recombinant tissue-type plasminogen activator (rt-PA) (two cases) or streptokinase (one case), anticoagulation with heparin (all cases) and aspirin (three cases). As soon as pericardial effusion was established by echocardiography, emergency percutaneous pericardiocentesis was performed at the bedside 20 +/- 6 h after thrombolytic therapy was started. This corrected immediately the clinical and hemodynamic status of each patient and a catheter was left in the pericardial space for 34 +/- 18 h. Thus, in the presence of unexplained clinical and hemodynamic deterioration occurring during the first 24 h after thrombolytic treatment of a large myocardial infarction, cardiac tamponade should be suspected. Immediate percutaneous pericardiocentesis followed by continuous drainage is a simple and definitive treatment for this complication.

Comparison of front-loaded recombinant tissue-type plasminogen activator, anistreplase and combination thrombolytic therapy for acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) 4 trial.

OBJECTIVES: The aim of our study was to determine a superior thrombolytic regimen from three: anistreplase (APSAC), front-loaded recombinant tissue-type plasminogen activator (rt-PA) or combination thrombolytic therapy. BACKGROUND: Although thrombolytic therapy has been shown to reduce mortality and morbidity after acute myocardial infarction, it has not been clear whether more aggressive thrombolytic-antithrombotic regimens could improve the outcome achieved with standard regimens. METHODS: To address this issue, 382 patients with acute myocardial infarction were randomized to receive in a double-blind fashion (along with intravenous heparin and aspirin) APSAC, front-loaded rt-PA or a combination of both agents. The primary end point "unsatisfactory outcome" was a composite clinical end point assessed through hospital discharge. RESULTS: Patency of the infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) at 60 min after the start of thrombolysis was significantly higher in rt-PA-treated patients (77.8% vs. 59.5% for APSAC-treated patients and 59.3% for combination-treated patients [rt-PA vs. APSAC, p = 0.02; rt-PA vs. combination, p = 0.03]). At 90 min, the incidence of both infarct-related artery patency and TIMI grade 3 flow was significantly higher in rt-PA-treated patients (60.2% had TIMI grade 3 flow vs. 42.9% and 44.8% of APSAC- and combination-treated patients, respectively [rt-PA vs. APSAC, p < 0.01; rt-PA vs. combination, p = 0.02]). The incidence of unsatisfactory outcome was 41.3% for rt-PA compared with 49% for APSAC and 53.6% for the combination (rt-PA vs. APSAC, p = 0.19; rt-PA vs. combination, p = 0.06). The mortality rate at 6 weeks was lowest in the rt-PA-treated patients (2.2% vs. 8.8% for APSAC and 7.2% for combination thrombolytic therapy [rt-PA vs. APSAC, p = 0.02; rt-PA vs. combination, p = 0.06]). CONCLUSIONS: Front-loaded rt-PA achieved significantly higher rates of early reperfusion and was associated with trends toward better overall clinical benefit and survival than those achieved with a standard thrombolytic agent or combination thrombolytic therapy. These findings support the concept that more rapid reperfusion of the infarct-related artery is associated with improved clinical outcome.

Current issues concerning thrombolytic therapy for acute myocardial infarction.

Data are now available from three large-scale randomized trials that directly compare the risks and benefits of thrombolytic agents in acute myocardial infarction. In the interpretation of results from the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) trial and its International Extension, the Third International Study of Infarct Survival (ISIS-3), and the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) trial, there are areas of both agreement and controversy. It is generally agreed that the agents most commonly used in the United States--tissue-type plasminogen activator (t-PA), streptokinase and anisoylated plasminogen streptokinase activator complex (APSAC)--all reduce mortality when given to patients with acute evolving myocardial infarction. Further, it is clear that thrombolytic therapy given to such patients presenting up to 12 h after onset of symptoms reduces the mortality rate by approximately 20%, that aspirin therapy for patients presenting up to 24 h reduces the mortality rate by approximately 23% and that the benefits of thrombolytic therapy and aspirin are additive. Finally, and of most importance, the earlier administration as well as the more widespread use of thrombolytic therapy and aspirin would save many more lives. The totality of evidence clearly indicates that streptokinase produces significantly fewer strokes and cerebral hemorrhages than either t-PA or APSAC. Whether or not accelerated t-PA has a small advantage for mortality is less conclusive.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved thrombolysis in acute myocardial infarction with front-loaded administration of alteplase: results of the rt-PA-APSAC patency study (TAPS)

Thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and anisoylated plasminogen streptokinase activator (APSAC) in myocardial infarction has been proved to reduce mortality. A new front-loaded infusion regimen of 100 mg of rt-PA with an initial bolus dose of 15 mg followed by an infusion of 50 mg over 30 min and 35 mg over 60 min has been reported to yield higher patency rates than those achieved with standard regimens of thrombolytic treatment. The effects of this front-loaded administration of rt-PA versus those obtained with APSAC on early patency and reocclusion of infarct-related coronary arteries were investigated in a randomized multicenter trial in 421 patients with acute myocardial infarction. Coronary angiography 90 min after the start of treatment revealed a patent infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3) in 84.4% of 199 patients given rt-PA versus 70.3% of 202 patients given APSAC (p = 0.0007). Early reocclusion within 24 to 48 h was documented in 10.3% of 174 patients given rt-PA versus 2.5% of 163 patients given APSAC. Late reocclusion within 21 days was observed in 2.6% of 152 patients given rt-PA versus 6.3% of 159 patients given APSAC. There were 5 in-hospital deaths (2.4%) in the rt-PA group and 17 deaths (8.1%) in the APSAC group (p = 0.0095). The reinfarction rate was 3.8% and 4.8%, respectively. Peak serum creatine kinase and left ventricular ejection fraction at follow-up angiography were essentially identical in both treatment groups. There were more bleeding complications after APSAC (45% vs. 31%, p = 0.0019).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical risks of thrombolytic therapy.

Understanding the clinical risks of intravenous thrombolytic therapy is critical to appropriate patient selection. The major risks can be classified into 5 major categories: intracranial hemorrhage, systemic hemorrhage, immunologic complications, hypotension, and myocardial rupture. Although theoretical concern exists about thromboembolic complications, they rarely occur. Although cardiac rhythm disturbances are somewhat more likely to occur at the time of reperfusion, the clinical significance of "reperfusion arrhythmias" is minimal. Intracranial hemorrhage, the most devastating complication, occurs in 0.2-1% of patients treated with thrombolytic therapy. Factors associated with incremental risk are now being identified from large clinical trials. Systemic hemorrhage is uncommon in patients without major vascular punctures and seldom leads to serious adverse outcomes. Immunologic complications--including anaphylaxis, which is rare, and immune complex disease, which is more common--occur only with streptokinase or agents with a streptokinase moiety, including anistreplase (anisoylated plasminogen--streptokinase activator complex, APSAC). Hypotension, which can be managed easily in most patients, is also observed much more frequently with streptokinase and anistreplase. Myocardial rupture is increasingly being recognized as a possible complication of late thrombolysis. A proper perspective on clinical risk can only be gained in the context of potential benefit of therapy. In many cases individual patients considered to be at highest risk for complications also stand to gain the most from treatment. Many of the questions raised by currently available data about bleeding risk are being addressed in the ongoing Global Utilization of t-PA and Streptokinase (GUSTO) Trial. A paradigm for considering this decision making problem is presented.

Angiographically assessed coronary arterial patency and reocclusion in patients with acute myocardial infarction treated with anistreplase: results of the anistreplase reocclusion multicenter study (ARMS).

In this open multicenter study, 156 patients with acute myocardial infarction received 30 U of anistreplase intravenously over 5 minutes within 4 hours of the onset of chest pain. The patency of the infarct-related vessel was determined by coronary angiography 90 minutes after anistreplase treatment, and also 24 hours after treatment, in patients with a patent infarct-related vessel at 90 minutes, to assess the reocclusion rate. The investigators categorized the infarct-related vessel as patent or occluded, and 2 independent cardiologists graded the infarct-related vessel according to the Thrombolysis in Myocardial Infarction (TIMI) perfusion criteria. At the 90-minute assessment, 106 of 145 evaluable patients (73%) had patent infarct-related vessels, and 39 of 145 (27%) had occluded infarct-related vessels. Of the 139 independently assessed patients, 98 (71%) had TIMI grades 2 or 3 and 41 (29%) had TIMI grades 0 or 1. At the 24-hour assessment, 98 of 102 patients (96%) had a patent infarct-related vessel, and reocclusion had occurred in 4 of 102 patients (4%). Of the 94 independently assessed patients 90 (96%) had TIMI grades 2 or 3, and 4 (4%) had TIMI grades 0 or 1. The reliability of noninvasive parameters as indicators of achieved patency of the infarct-related vessel was estimated by means of correlation with patency assessed by coronary angiography. A significant correlation of 0.62 was found. The patency rate of 71 to 73% after use of anistreplase in patients with acute myocardial infarction corresponds with findings in earlier studies. The low reocclusion rate of 4% after use of anistreplase probably reflects the prolonged action of anistreplase.

Comparison of results of intravenous infusion of anistreplase versus streptokinase in acute myocardial infarction.

This randomized study compares the coronary perfusion rate in patients with acute myocardial infarction (AMI) treated with 2 different intravenous thrombolytic agents: streptokinase 1.5 million U given over 60 minutes and anisoylated human plasminogen streptokinase activator complex (anistreplase) administrated as a bolus of 30 U over 5 minutes. One hundred seventy-five patients (149 men and 26 women, mean age 54 years) have been included in this study. Eighty-nine patients were treated with anistreplase and 86 patients with streptokinase. AMI was inferior in 54 patients (61%) in the anistreplase group and in 54 patients (63%) in the streptokinase group. It was anterior in 35 (40%) and 32 (37%) patients, respectively. Coronary angiography and ventriculography were performed at a mean time (+/- SEM) of 207 +/- 11 minutes after the beginning of thrombolysis in 170 patients. A perfusion score grade of 2 or 3 according to the Thrombolysis in Myocardial Infarction trial was found in 63 patients (72%) in the anistreplase group and in 56 patients (68%) in the streptokinase group (p = NS). Severe bleeding occurred in 7 patients (8%) after anistreplase and in 6 patients (7%) after streptokinase. No cerebral hemorrhage occurred. Nine patients (5%) died during their hospital stay: 6 after anistreplase and 3 after streptokinase. It is concluded that intravenous administration of anistreplase or streptokinase is efficient and safe. Coronary patency 207 minutes after fibrinolysis, incidence of adverse events and mortality are similar in both groups.

Anistreplase in early acute myocardial infarction and the one-year follow-up.

Of consecutive patients seen with first myocardial infarction (88 of whom were treated out-of-hospital by mobile coronary care staff), 139 received 30 units of intravenous anistreplase at a mean of 101 minutes (range 35-180) from onset of symptoms. Thrombolysis in myocardial infarction patency grade 2 or 3 was found in 76/91 (83.5%) patients. At 3-4 months after hospital discharge, the mean global left ventricular ejection fraction and mean infarct-related regional third ejection fraction declined with increasing delay to anistreplase. For the first, second and third hour administrations, global ejection fraction was 54%, 50% and 45% (P = 0.002) and for regional third ejection fractions 49%, 43% and 41% (P = 0.02) respectively. Of the patients, 130 were reviewed at approximately 1 year: reinfarction had occurred in 9, 6 had undergone coronary angioplasty and 1 had coronary arterial bypass grafting performed since discharge. Mean global left ventricular ejection fraction was 52% and mean infarct-related regional third ejection fraction was 51%. Thus, intravenous anistreplase induces high rates of arterial patency. Global and regional third ejection fractions decline with increasing delay in the time of administration of anistreplase. Mortality and morbidity is low in the first year.

The European Myocardial Infarction Project: an assessment of pre-hospital thrombolysis.

The use of thrombolytic agents in patients with suspected myocardial infarction has been shown to reduce early and long-term mortality by about 20%, and it has been suggested that since time is an important factor, pre-hospital treatment would give better results. However, health deciders need reliable data on which to base future policies concerning this. The European Myocardial Infarction Project was a European Economic Community-supported double-blind study designed to evaluate the efficacy and safety of pre-hospital early thrombolytic treatment in patients with suspected myocardial infarction compared with the same treatment given later in a hospital setting. A total of 5469 patients in 16 countries were randomised by 198 mobile emergency units to receive either pre-hospital treatment with anistreplase, the thrombolytic agent used, followed by placebo after hospital admission (pre-hospital group; 2750 patients), or placebo followed by anistreplase (hospital group; 2719 patients). The median time delay between the injections was 55 min. A non-significant decrease in 30-day mortality was observed in favour of the pre-hospital group (13%: P = 0.08), whereas the decrease in cardiac death observed, also in favour of the pre-hospital group, was on the borderline of significance (16%; P = 0.049). Although some complications occurred more frequently in the pre-hospital group in the pre-hospital period, the overall incidence for serious complications was similar for both groups. These results show that the pre-hospital thrombolytic strategy in patients with suspected myocardial infarction is both effective and safe when performed by well-equipped well-staffed mobile emergency units.

Prehospital thrombolysis in rural emergency room and subsequent transport to a coronary care unit: Ravenna Myocardial Infarction (RaMI) trial.

OBJECTIVE: To assess the feasibility, safety and efficacy of thrombolysis in the Emergency Room of a Rural Hospital with no Coronary Care Unit, and subsequent transfer to the Coronary Care Unit of a City Hospital. DESIGN: Prospective study, controlled with two parallel groups of consecutive patients (Group 1: Rural Hospital, Group 2: CCU Ravenna) and administration of Anistreplase 30 intravenous unit. SETTING: Rural Emergency Rooms which transmitted the electrocardiogram by cardiotelephone to the Ravenna Coronary Care Unit (average distance 35 km; range: 17-50 km). PATIENTS: 280 (Group 1: 102 patients, Group 2: 178 patients) with suspected acute myocardial infarction and with no contra-indications to fibrinolysis, within 6 h of onset of symptoms. MAIN OUTCOME MEASURES: time saving, accuracy of diagnosis, adverse events, left ventricular function and survival. RESULTS: the median pain to needle time was 90' in Group 1 and 165' in Group 2 (P < 0.001). Accuracy of diagnosis for acute myocardial infarction was 91% and 100%, respectively. Complications were rare and none occurred during transfer. The creatine phosphokinase peak of Group 1 was lower than Group 2 (1389 vs. 2186 IU/l; P < 0.001). The echocardiographic Wall Motion Abnormality Score Index of Group 1 was lower than Group 2 (3.571 vs. 5.589; P < 0.001). Mortality at 35 days in Group 1 was 7.5% vs. 10.7% in Group 2 (-30%; P = n.s.). CONCLUSIONS: The Emergency Room physician, in close collaboration with the cardiologist, supplied a very high standard of pre-Coronary Care Unit diagnosis and therapy. Administration of Anistreplase in the rural Emergency Room brought about a significant reduction of pain to needle time, a significant improvement in left ventricular function and a reduction in mortality.

Assessment of the practicality and safety of thrombolysis with anistreplase given by general practitioners.

BACKGROUND: Recent guidelines recommend that patients with obvious acute myocardial infarction receive thrombolysis, unless contraindicated, within 60-90 minutes of summoning assistance. If this target is to be achieved, an increasing number of general practitioners are likely to be involved in the administration of thrombolytic agents. AIM: This study aimed to assess the practicality and safety of thrombolysis with anistreplase when given by general practitioners. METHOD: An observational study was conducted in 805 general practices throughout the United Kingdom. Between March 1991 and September 1992, a total of 3383 patients with a clinical diagnosis of myocardial infarction were recruited--888 by 344 general practitioners who wished to include anistreplase in their management of myocardial infarction ('user' group) and 2495 by 776 general practitioners who did not wish to use anistreplase but who were willing to provide information about their cases ('comparison' group). RESULTS: More than half the patients were seen within two hours of onset of symptoms. A high frequency of contra-indications to thrombolysis, diagnostic uncertainty, and other, mainly practical, reasons limited the number of occasions on which anistreplase was administered. Thus, only 310 patients were given anistreplase in the community. The general practitioners in the study used anistreplase safely. Their diagnostic accuracy was high (of the 310 patients given anistreplase 69% had a definite, possible or probably myocardial infarction, 4% a definite non-cardiac diagnosis), the number of patients given anistreplase in spite of a documented contraindication was small (seven patients), and the doctors appeared to be aware of potential bleeding problems associated with thrombolysis. In all cases, the complications of acute myocardial infarction appeared to be managed appropriately. CONCLUSION: General practitioners can use anistreplase both appropriately and safely in the early management of acute myocardial infarction. Recognized contraindications to thrombolysis and practicalities of diagnosis and drug administration may, however, limit the number of occasions on which anistreplase is used.

Short- and long-term comparative study of anistreplase versus streptokinase in acute myocardial infarction.

Streptokinase is well established as an effective thrombolytic. Anistreplase, a new thrombolytic drug, is a complex of streptokinase and acylated human plasminogen that can be administered by intravenous bolus and activates plasminogen at the clot site. Although both streptokinase and anistreplase are effected in treating myocardial infarction (MI), they have different pharmacologic properties. This study was designed to identify short- and long-term differences in their clinical effectiveness, safety in use, and survival rates in patients with acute MI. One hundred ten successive patients under seventy years of age admitted within three hours after onset of sustained chest pain suggestive of acute MI were randomized to receive either 30 units of anistreplase intravenously over five minutes or intravenous injection of 750,000 units of streptokinase over thirty to sixty minutes. Reperfusion was achieved in 34 of the 52 (65%) patients treated with anistreplase and in 41 of the 58 (71%) patients treated with streptokinase (p = NS). The two drugs were equally effective in preserving left ventricular ejection fraction, which was found to be significantly better in patients with anterior wall MI who had achieved reperfusion than it was in those who did not (p less than 0.02). One-month, twelve-month, and thirty-six-month survival rates were high (96% to 88%) with no significant difference between the two treatment groups. The authors conclude that the two drugs are equally effective thrombolytic agents but that anistreplase has the advantage that it can be administered as a bolus injection.

[The adult respiratory distress syndrome as a complication of the APSAC treatment of acute myocardial infarct. Apropos a case]. / Síndrome de distrés respiratorio del adulto como complicación del tratamiento del infarto agudo de miocardio con APSAC. A propósito de un caso.

Thrombolytic therapy has shown to be effective in acute myocardial infarction, and its benefits on left ventricular function and later survival are well known. However it is not a therapy free of complications and side effects. Allergic reactions, anafilaxia, hypotension, and several kinds of hemorrhages have been reported. Adult respiratory distress syndrome after streptokinase administration has been also described, and one case, recently communicated, after APSAC therapy. We present the case of a male with acute myocardial infarction who developed adult respiratory distress syndrome after APSAC therapy, with different outcome than the first case published in the literature. Finally, we discussed the mechanisms by means these drugs can produce such a complication.

[Hypersensitivity vasculitis after thrombolytic therapy with APSAC (anisoylated plasminogen streptokinase activator complex). Presentation of a clinical case and review of the literature]. / Vasculite da ipersensibilità post-terapia trombolitica con APSAC (anisoylated plasminogen streptokinase activator complex). Presentazione di un caso clinico e revisione della letteratura.

We describe a rare case of hypersensitivity vasculitis associated with APSAC administration in a 54-year-old man. Fifteen days after receiving thrombolytic therapy (APSAC 30 U) for acute myocardial infarction, the patient was admitted to our department for myalgia, livedo reticularis and erythema of the legs with an ulcerative necrotic lesion of the fifth toe of the right foot. The presence of circulating immune complexes at high titer supported the diagnosis of hypersensitivity vasculitis.

Feasibility, safety, and efficacy of domiciliary thrombolysis by general practitioners: Grampian region early anistreplase trial. GREAT Group.

OBJECTIVE: To assess the feasibility, safety, and efficacy of domiciliary thrombolysis by general practitioners. DESIGN: Randomised double blind parallel group trial of anistreplase 30 units intravenously and placebo given either at home or in hospital. SETTING: 29 rural practices in Grampian admitting patients to teaching hospitals in Aberdeen (average distance 36 (range 16-62) miles). PATIENTS: 311 patients with suspected acute myocardial infarction and no contraindications to thrombolytic therapy seen at home within four hours of onset of symptoms. MAIN OUTCOME MEASURES: Time saving, adverse events, Q wave infarction, left ventricular function. RESULTS: Anistreplase was administered at home 101 minutes after onset of symptoms, while anistreplase was given in hospital 240 minutes after onset of symptoms (median times). Adverse events after thrombolysis were infrequent and, apart from cardiac arrest, not a serious problem when they occurred in the community: seven of 13 patients were resuscitated after cardiac arrest out of hospital. By three months after trial entry the relative reduction of deaths from all causes in patients given thrombolytic therapy at home was 49% (13/163 (8.0%) v 23/148 (15.5%); difference -7.6% (95% confidence interval -14.7% to -0.4%), p = 0.04). Full thickness Q wave infarction was less common in patients with confirmed infarction receiving treatment at home (65/122 (53.3%) v 76/112 (67.9%); difference -14.6% (95% confidence interval -27.0% to -2.2%), p = 0.02). CONCLUSIONS: General practitioners provided rapid pre-hospital coronary care of a high standard. Compared with later administration in hospital, giving anistreplase at home resulted in reduction in mortality, fewer cardiac arrests, fewer Q wave infarcts, and better left ventricular function. Benefits were most marked where thrombolytic therapy was administered within two hours of the onset of symptoms.