Streptokinase and tissue plasminogen activator in acute myocardial infarction

The use of thrombolytic agents for the treatment of myocardial infarction is increasing. Many community hospitals are infusing SK intravenously and those with cardiac catheterization laboratories often use intracoronary SK and angioplasty. Tissue plasminogen activator is undergoing extensive clinical trials, and reports of this research should add to our knowledge of this new therapy. Recently, benefits from thrombolytic therapy such as increased ejection fraction, improved regional wall motion, and short-term decreases in mortality have been documented. Both the GISSI trial that recruited 11,712 patients in Italy and the Netherlands trial documented significant short-term decreases in mortality after therapy with SK compared with control groups. As this information reaches the medical community, we may see an increase in the use of thrombolytic therapy during acute myocardial infarction. Additionally, community education service organizations should reemphasize the importance of seeking help early after the signs and symptoms of acute myocardial infarction appear to promote early treatment and potential salvage of greater amounts of myocardium. The long-term prognosis of patients who have been successfully reperfused and the best management after thrombolytic therapy is not yet known. Future problems and benefits from this therapy are still to be determined.     

Community hospital experience with recombinant tissue plasminogen activator in acute myocardial infarction

Clinical features, outcomes, and hospital charges of 51 consecutive patients who had had acute myocardial infarction (MI) and who had received intravenous tissue plasminogen activator (TPA) at a community teaching hospital were reviewed retrospectively. The overall mortality rate was 22%, including four patients (8%) who had died of hemorrhagic complications, three of whom (6%) had had intracerebral hemorrhages. Despite similar mean ages and lengths of hospital stay, TPA patients had had significantly higher total hospital charges and ancillary charges than had had concurrent MI patients who had not received TPA (p less than 0.0001). In a community hospital setting, older patients may be at higher risk for intracranial hemorrhage when treated with TPA, especially in the presence of other risk factors.     

Coronary patency after intravenous infusion of recombinant tissue-type plasminogen activator in acute myocardial infarction

The relation between coronary patency after infusion of recombinant tissue-type plasminogen activator (rt-PA) and clinical and laboratory findings was assessed in patients with acute myocardial infarction. This study focused primarily on information available early in the hospitalization phase. Data were available for 243 patients who received the full dose of rt-PA and who had assessable coronary angiograms 90 min after the start of the intravenous infusion. The infarct-related vessel was scored by an independent assessment committee as being patent in 65% of patients. The left anterior descending coronary artery was involved in 53% of patients, and proximal localization of the infarct-related vessel occurred in 65%. In the majority of patients (85%), the infusion was started within 4 h of the acute event. Neither the angiographic location of the infarct-related vessel nor electrocardiographic evidence of infarct severity or location appeared to have a bearing on thrombolysis with rt-PA. Multivariate logistic regression analysis identified three independent predictors of coronary patency: hematocrit 43 to 47%, blood plasminogen level greater than or equal to 90% of normal and serum alkaline phosphatase greater than or equal to 82% of the local upper normal limit. In addition, the use of intravenous nitrates suggests a positive association with patency.     

Use of tissue plasminogen activator in the emergency department for acute myocardial infarction

Tissue plasminogen activator (t-PA) is a new intravenously administered thrombolytic agent currently being tested for emergency treatment of acute myocardial infarction (AMI). This report summarizes our clinical experience using t-PA to treat AMI in the emergency department and describes current protocols for its use in treating AMI. Between September 1985 and August 1986, t-PA was administered to 105 patients with AMI according to clinical research protocols. All were treated within six hours of the onset of pain. Thrombolysis was achieved in 80 patients (76%). Percutaneous transluminal coronary angioplasty was performed acutely for residual stenosis in 58 (55%). Thirty-three patients (31%) exhibited cardiac arrhythmias during treatment, 18 (17%) requiring emergency intervention. Periaccess hematoma developed in 50 patients (48%); transfusion of one or more units of blood was required in 22 of 97 (23%), excluding those undergoing urgent coronary artery bypass grafting. Overall 30-day survival was 94%. Recombinant t-PA appears to be an effective thrombolytic agent that may soon be standard emergency therapy for patients with AMI. Administration begun in the ED can achieve a high rate of reperfusion, but requires careful monitoring and the support of a coordinated acute cardiac care program, including emergency cardiac catheterization and cardiac surgery, to achieve the best results.     

Anaphylactoid reaction during an infusion of recombinant tissue-type plasminogen activator for acute myocardial infarction

Potentially life-threatening immediate hypersensitivity reactions are extremely rare among patients treated with thrombolytic agents for suspected acute myocardial infarction. A patient who developed a severe reaction during an infusion of recombinant tissue-type plasminogen activator is described. Potential causal mechanisms for the reaction could be related either to nonmedicinal additives or complement activation. Implications for treatment in the setting of acute myocardial infarction are discussed.     

Reduced synthesis of tissue plasminogen activator by vascular endothelium during acute myocardial infarction

We management levels of tissue plasminogen activator (t-PA) antigen in 100 patients within six hours of the onset of acute myocardial infarction, in 34 patients with chronic angina but no recent infarction, and in 36 normal subjects. We also assayed von Willebrand factor in the acute patients and in the normal subjects. Measurements were repeated in 40 acute patients at three weeks after myocardial infarction. Although resting levels of t-PA antigen were not significantly different from normal during myocardial infarction, the capacity of the vascular endothelium to release t-PA after five minutes of venous occlusion was impaired ( P <0.01). The acute phase vessel wall release of von Willebrand factor was increased during acute iafarction ( p <0.01). We conclude that impairment of t-PA production is associated with acute coronary thrombosis although it is not possible to differentiate between a causative role or a secondary response due to exhaustion of the t-PA producing mechanism.     

Spinal epidural hematoma following tissue plasminogen activator and heparinization for acute myocardial infarction

The case of a 43-year-old Taiwanese man who presented with spinal epidural hematoma following intravenous administration of recombinant tissue plasminogen activator (rTPA) and heparin therapy for acute myocardial infarction (AMI) is reported. Upper back pain and progressive neurological dysfunction ensued, secondary to spinal epidural hematoma with spinal cord compression. The patient did not recover neurologic function postsurgically, possibly because the operation was delayed. In conclusion, cardiologists should be alert to this rare, severe complication of rTPA and should perform early laminectomy (in < or = 36 hours for those with complete deficit and in < or = 48 hours for those with incomplete deficit) if possible.     

Recombinant tissue plasminogen activator in acute myocardial infarction in the Chinese in Hong Kong.

Eighty-nine consecutive Chinese patients (69 males, 20 females) with acute myocardial infarction treated by 100 mg recombinant tissue plasminogen activator (7 intracoronarily, 82 intravenously) at 3.7 +/- 1.0 h after onset, and intravenous heparin or dipyridamole therapy started at 3 h, were studied prospectively. Their mean age was 59.6 +/- 10.6 yr. Forty-six patients (51.7%) had anterior and 39 patients (43.8%) had inferior infarcts. Clinical evidence of reperfusion were seen in 63 patients (70.8%), while new complications included hypotension (5.6%), heart failure (6.7%), cardiac arrhythmias (76.4%) majority of which are related to reperfusion and self-remitting, haematoma around vascular access sites (23.6%), melaena (3.3%) and cerebral infarction (2.2%). Maximal changes in coagulation profiles were seen at 3 h, including a decrease in fibrinogen by 64.2% and an increase in fibrin degradation products by 47 times. The changes in haemostatic variables were not related to body weight or bleeding complications. Nine patients (10.1%) had recurrence of angina and 6 patients (6.9%) died due to pump failure and reinfarction. Angiogram at 14 days confirmed TIMI 2 or 3 patency of infarct-related arteries in 63 out of 73 (86.3%) patients, with a mean global ejection fraction of 52.5 +/- 12.4%. Nearly all survivors could maintain class I-II functional status after discharge. The safety and promise of recombinant tissue plasminogen activator for acute myocardial infarction in the Chinese were confirmed.     

Comparison of two dose regimens of intravenous tissue plasminogen activator for acute myocardial infarction

Two dosing schedules of intravenous tissue plasminogen activator (t-PA) for acute myocardial infarction were compared in a multicenter trial. At 2.95 +/- 1.1 hours from onset of chest pain, 386 patients received 150 mg of intravenous t-PA. For the first 178 patients (group A), 60 mg were given in the first-hour dose and the remaining 90 mg were infused over 7 hours. In the subsequent 208 patients (group B), the first-hour dose was 1.0 mg/kg and the remaining 150 mg were given over 5 hours. At initial angiography 94 +/- 30 minutes into therapy, the infarct vessel patency was 64% in group A versus 75% in group B (p = 0.02). By final angiography with up to 4 selective contrast injections, patency was 68% versus 77%, respectively (p = 0.06). Repeat angiography at 7 to 10 days demonstrated reocclusion in 17% of group A and 13% of group B patients (p = 0.35). There was no difference in fibrinogen nadir or mean hematocrit drop between the 2 groups: 120 mg/dl and 11 points, respectively, in group A compared with 120 mg/dl and 10 points in group B. However, bleeding was reduced in group B patients as evident by a decrease in requirement for greater than or equal to 2 units of packed red blood cell transfusion (group A 36%, group B 27%, p = 0.05) and lower incidence of gastrointestinal bleeding (group A 12%, group B 4%, p = 0.002). To further study the importance of weight adjustment, patients were divided into 2 groups according to weight (less than or equal to 90 kg versus greater than 90 kg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Spinal epidural hematoma associated with tissue plasminogen activator treatment of acute myocardial infarction.

We report a case of tissue plasminogen activator-associated spinal epidural hematoma in a patient who underwent treatment for myocardial infarction. Diagnostic magnetic resonance imaging was used within 24 hr of coronary artery stent implantation. We review the literature on thrombolytic-associated epidural spinal hematoma and discuss its management. Cathet. Cardiovasc. Intervent. 48:390-396, 1999.     

Intravenous recombinant tissue-type plasminogen activator in acute myocardial infarction]

The efficacy and safety of intravenous administration of recombinant tissue-type plasminogen activator (rt-PA, made by Boehringer Ingelheim Corp.) was investigated in 10 patients with acute myocardial infarction (AMI). The rt-PA was given as a bolus dose of 10 mg followed by an infusion of 50 mg, 20 mg and 20 mg in successive hours. Heparin and aspirin were given to all the patients. The time interval from the onset of chest pain to thrombolysis was from 2.3 to 6.1 h with mean of 3.9 h. Coronary angiography, performed before administration of rt-PA and every 30 minutes thereafter, demonstrated total coronary occlusion (grade O) in 9 patients and grade 1 in 1 at baseline study. The infarct-related coronary artery were LAD in 5, RCA in 3 and LCX in 2. At 90 minutes after infusion of rt-PA reperfusion of the infarct-related artery was observed in 7 patients, the success rate was 70%. In one case the infarct-related LCX was not opened at 90 minutes, but it was reperfused at 170 minutes, after intracoronary administration of 10 mg of rt-PA. The total dose in this case was 130 mg. During 30 days of hospitalization death occurred in only one case with cardiogenic shock, in whom the infarct-related RCA was not reperfused by rt-PA but was successfully recanalized by PTCA. The patient died from rupture of the left ventricle on the 4th day. No patient had clinical evidence of reinfarction. Follow-up angiography in 2 patients showed that the arteries reperfused initially were patent.(ABSTRACT TRUNCATED AT 250 WORDS)     

One-year follow-up after recombinant tissue plasminogen activator administered to patients with acute myocardial infarction

Of 106 patients seen within 4 h of chest pain with 107 episodes of acute myocardial infarction, nine died before or during hospitalization mainly from cardiogenic shock, and four died during the next year, three were sudden deaths. The 93 survivors were reviewed at a mean of 53 (range 49-70) weeks after infarction. Of these 93, 18 had had attempted angioplasty (successful in 12) and 15 had had coronary artery bypass grafting (including one patient who had coronary artery bypass grafting performed after unsuccessful angioplasty). The remaining 61 patients continued on medical therapy only. During the one-year follow-up two patients suffered reinfarction and a further 22 had one or more cardiac admissions, mostly for chest pain. At review, 22 patients had angina (16 New York Heart Association Grade I or II) and five dyspnoea (all NYHA Grade II). Forty-three patients were taking oral nitrates, 53 were receiving calcium antagonists, 54 were using betablocking agents and 73 used anti-platelet agents. However, many of these patients continued on anti-anginal therapy prophylactically after their myocardial infarction, without continuing chest pain. Thus after recombinant tissue plasminogen activator therapy and following hospital discharge the mortality rate for patients with acute myocardial infarction was four out of 97 (4.1%) and reinfarction rate among survivors was two out of 93 (2.2%). Although the incidence of cardiac symptoms was low this may be partly due to the high incidence of angioplasty and coronary artery grafting, together with the use of anti-anginal agents.     

重组组织型纤溶酶原激活剂静脉溶栓治疗急性心肌梗死20例分析

目的 :探讨重组组织型纤溶酶原激活剂 (rt PA)静脉溶栓治疗急性心肌梗死 (AMI)的疗效及安全性。方法 :选择 2 0例AMI患者应用rt PA静脉溶栓治疗 ,观察临床症状、心电图、心肌酶谱的变化 ,判断冠状动脉再通率。结果 :① 2 0例AMI患者 ,冠状动脉再通 12例 ,再通率 6 0 %,其中发病 6h以内溶栓再通率 87.5 %(7/ 8) ,发病 6～ 2 4h溶栓再通率 4 1.7%(5 / 12 ) ,两者相比差异有显著性意义 (P <0 .0 5 )。②≤ 6 5岁患者的血管再通率与不良反应发生率与 >6 5岁组相比差异无显著性意义 (P >0 .0 5 )。结论 :rt PA静脉溶栓治疗AMI是一种安全、有效的方法 ,宜提倡急诊室溶栓。 >6 5岁患者行静脉溶栓治疗是安全可行的 ,但要根据患者的具体情况而定。     

Cardiac morphologic findings in patients with acute myocardial infarction treated with recombinant tissue plasminogen activator

The hearts of 52 patients (aged 61 +/- 11 years, 34 men) who participated in the Thrombolysis in Myocardial Infarction (TIMI) Study and died from 5 hours to 260 days (median 2.7 days) after onset of chest pain were studied. One heart became available at cardiac transplantation. Of the 52 patients, 38 received recombinant tissue plasminogen activator (rt-PA) not followed by percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG). Eight had PTCA, and 6 had CABG. The infarcts were hemorrhagic by gross inspection (with histologic confirmation) in 23 patients, nonhemorrhagic in 20, not visible grossly in 2 and, in 7, there was no myocardial necrosis by either gross or histologic examination.(ABSTRACT TRUNCATED AT 250 WORDS)     

Limitation of myocardial infarction by early infusion of recombinant tissue-type plasminogen activator

In a double-blind randomized trial involving five Sydney hospitals and the city ambulance paramedical service, 145 patients with a first evolving myocardial infarction and with onset of pain less than 2.5 (mean 1.9 +/- 0.5 [SD]) hr previously were allocated to intravenous infusion of 100 mg recombinant tissue-type plasminogen activator (rt-PA) or placebo over 3 hr. The groups at entry were similar. At assessment 21 days later, left ventricular ejection fraction measured both by contrast and radionuclide ventriculography was higher in the rt-PA compared with the placebo group (61 +/- 13%, n = 64, vs 54 +/- 14%, n = 62, contrast, 2p = .006; 52 +/- 13%, n = 66, vs 48 +/- 13%, n = 62 isotope, 2p = .08). This indicates limitation of myocardial infarction by rt-PA.     

Effects of tissue-type plasminogen activator and anisoylated plasminogen streptokinase activator complex on mortality in acute myocardial infarction

An overview of eight randomized controlled trials of tissue-type plasminogen activator (Alteplase or Duteplase) and 10 of anisoylated plasminogen streptokinase activator complex (Anistreplase) showed that the odds of early death were reduced by 29% by tissue-type plasminogen activator and 46% by anisoylated plasminogen streptokinase activator complex, with overlapping 95% confidence intervals. Although the beneficial effects of both agents are consistent and are strengthened when all the trials are considered together, the available data do not permit comparisons of the relative efficacy of these two agents with each other or with streptokinase.     

Potential cost effectiveness of intravenous tissue plasminogen activator versus streptokinase for acute myocardial infarction.

OBJECTIVE: An economic evaluation of the potential incremental benefits of intravenous tissue plasminogen activator (tPA) versus streptokinase (SK) for treatment of acute myocardial infarction. DESIGN: Cost effectiveness analysis from a third-party payer perspective (Ontario Ministry of Health). ECONOMIC INPUTS: Fully allocated costs for cardiovascular procedures and hospitalization for myocardial infarction were obtained anonymously for four Ontario teaching hospitals and converted to 1988 Canadian dollars. Professional charges were taken from the provincial health insurance fee schedule and drug costs obtained from the manufacturers. CLINICAL INPUTS: The baseline analysis was for nonelderly patients with uncomplicated myocardial infarctions; sensitivity analyses allowed extrapolation to higher risk subgroups. Short and longer term mortality and short term invasive procedure rates were estimated using data from clinical trials. MAIN RESULTS: If tPA achieves a 1% short term mortality advantage over SK with no advantages for other survivors, cost per life-year gained can be comparable to other cardiovascular interventions at $58,600. In the absence of immediate survival advantages, but assuming greater left ventricular preservation, the constant annual hazard rate advantage must be about 0.5% per year for competitive cost effectiveness ratios. CONCLUSIONS: A full range of projections is presented to help guide the policy decisions that will arise in the wake of the Global Utilization of SK and tPA for Occluded Coronary Arteries (GUSTO) trial. The analysis also illustrates the general importance of considering longer term effects of in-hospital therapies for acute myocardial infarction.