尿激酶治疗急性心肌梗塞多中心临床试验1406例总结

为观察尿激酶天普洛欣（ＵＫＴＰ）经静脉溶栓治疗急性心肌梗塞（ＡＭＩ）的临床有效性及安全性。收集协作组１４８家医院１９９４年１１月至１９９６年４月经静脉ＵＫＴＰ溶栓治疗ＡＭＩ患者１４０６例，观察临床疗效、副作用及病死率等。其中１２４例行９０分钟冠状动脉造影评价梗塞血管开通情况。结果：梗塞血管临床再灌注率为７３．５％，９０分钟冠状动脉造影血管开通率为７２．６％，５周总病死率为７．８％（１０９／１４０６），轻度出血１０．２％（１４３／１４０６），中重度出血０．４３％（６／１４０６），脑出血０．５０％（７／１４０６）。老年（＞６５岁）甚至高龄（＞７５岁）患者溶栓及距发病超过６小时者，其用药仍然安全有效，ＵＫＴＰ合适的用药剂量可能为１５０万Ｕ左右。结果提示ＵＫＴＰ治疗ＡＭＩ安全有效。     

Saruplase Is a Safe and Effective Thrombolytic Agent; Observations in 1698 Patients: Results of the PASS Study

Saruplase (unglycosylated human-type high molecular weight single-chain urokinase-type plasminogen activator) was given to 1698 patients in the open-label Practical Applicability of Saruplase Study (PASS), which assessed the safety and efficacy of saruplase in the treatment of acute myocardial infarction. Thirty-seven hospitals in Europe participated in the study. All patients received 20 mg saruplase as a bolus followed by an infusion of 60 mg saruplase over 1 hour. Prior to the infusion of saruplase, 62% of the patients received a bolus of 5000 U of heparin, and after saruplase a 24-hour intravenous infusion of heparin was given to 95% of patients. The mean age of the patients was 59 years and 80.1% were male. The median delay from the onset of chest pain to the start of saruplase infusion was 145 minutes. Acute angiography was performed in 8 of the participating 37 centers in 350 patients (20.6%), on average 85 minutes (median) after the start of the saruplase infusion. TIMI 3 flow was obtained in 186 patients (53.1%) and TIMI 2 flow in 61 patients (17.4%). Patency rates were similar for patients with anterior and inferior infarction. ECG signs suggestive of reperfusion were seen in 63% of the patients. In-hospital mortality was low (92 patients; 5.4%), and nonfatal recurrent myocardial infarction was seen in 60 patients (3.5%). Severe bleeding complications occurred in 92 patients (5.4%), 21 of whom (1.2%) needed a blood transfusion. An intracerebral hemorrhage was observed in eight patients (0.5%), and seven patients (0.4%) suffered from a thromboembolic stroke. At discharge 85.9% of the patients were in NYHA functional class I. One-year mortality was low (142 patients; 8.4%). Mortality was high in patients with TIMI 0 or 1 flow at the acute angiography who did not undergo rescue PTCA (9/39; 23.1%), lower in patients with TIMI 0 or 1 flow followed by successful rescue PTCA (7/64; 10.9%), and low in patients with TIMI 2 flow (1/61; 1.6%) or with TIMI 3 flow (2/186; 1.1%). Patency rates and (bleeding) complications did not differ between patients with a body weight greater than or less than 70 kilograms. No antibodies against saruplase were detected in samples from 455 patients. In conclusion, it can be stated that saruplase, given in combination with aspirin and intravenous heparin, can be given safely and effectively to patients with acute myocardial infarction.     

尿激酶溶栓治疗急性心肌梗死的疗效观察

目的探讨应用尿激酶溶栓对急性脑梗死进行治疗所取得的临床效果,并对其治疗作用和意义进行分析总结。方法选择我院曾收治的急性心肌梗死患者62例,将其随机分为数量相等的两组,分别作为观察组和对照组,观察组中患者利用尿激酶溶栓来进行治疗,对照组患者利用常规方法来进行治疗。在完成治疗之后对两组患者的治疗效果进行比较分析,主要包括效果、引发症状以及并发症与血管再通率。结果对照组患者中有10例患者溶栓值趋于正常标准化,其标准率为32.3%,观察组中患者有21例的溶栓值趋于正常标准,其标准率为67.7%,两组患者之间存在显著差异;两组患者中的血管再通率分别为80.6%和38.7%,有显著差异存在;观察组中患者的引发症状以及并发症都较少,两组患者之间存在显著差异。结论对于急性心肌梗死患者来说,利用尿激酶溶栓进行治疗能够取得较好的效果,血管再通率较高,不会引发其它症状,所出现的并发症也比较少,比较安全,在临床医学上具有重要的作用和意义,值得在临床上进行推广。     

Comparison of the pharmacokinetics and effects on the hemostatic system of saruplase and urokinase in patients with acute myocardial infarction

The aim of the study was to compare in a single trial, using identical methodology, the pharmacokinetic properties and the effect on the hemostatic system of saruplase (unglycosylated scu-PA) and urokinase (glycosylated tcu-PA). Twenty-four patients with an acute myocardial infarction were either treated with saruplase (n = 12; 20 mg IV bolus followed by a 60 mg infusion for 60 minutes) or urokinase (n = 12; 1.5 million IU IV bolus followed by 1.5 million IU infusion for 60 minutes). Blood samples from saruplase-treated patients were analyzed for u-PA antigen and total u-PA and tcu-PA activities; those from urokinase-treated patients for u-PA antigen and tcu-PA activity. The effect of treatment on, including recovery of, plasma ₂-antiplasmin, fibrinogen, and plasminogen was examined in both groups. The total clearance of urokinase (179 ± 55 ml/ min) is about half that of saruplase (406 ± 154 ml/min), and the mean residence time of urokinase (59.1 ± 22.5 minutes) is nearly twice that of saruplase (28.3 ± 7.8 minutes), which results in a slower elimination of urokinase from plasma. Whether differences in the pharmacokinetic behavior of the unglycosylated saruplase and the glycosylated urokinase observed in this study are due to the difference in glycosylation or to other factors is not resolved. The systemic effect of saruplase on ₂,-antiplasmin, fibrinogen, and plasminogen is similar to that of urokinase, although retarded.     

尿激酶溶栓治疗急性脑梗死的临床疗效及安全性

目的 评估尿激酶静脉溶栓治疗急性脑梗死的疗效及安全性.方法 1995年3月至1999年6月收治62例急性脑梗死患者,男34例,女28例,平均年龄(66±9)岁.发病时间＜6 h者57例,6～9 h 4例,9～12 h 1例.随机分为溶栓组和对照组(各31例).用溶栓前后神经功能缺损的积分差值变化评估临床疗效并观察急性期并发症,采用Barthel指数及死亡率评估患者3个月时的疗效.结果 溶栓组急性期出现大量脑出血、全身性出血及症状再加重的发生率分别为3%、19%和26%.随访3个月,两组死亡率比较差异无显著性意义.溶栓组Barthel指数显著高于对照组.结论 尿激酶静脉溶栓治疗可使急性脑梗死患者神经功能缺损早期恢复,改善3个月时的预后;溶栓治疗的急性期有一定的并发症,特别是症状再加重的发生率较高.     

Electrophysiological effects of intravenous sotalol in acute myocardial infarction: a double-blind placebo-controlled study

Controlled studies of the electrophysiological effects of beta-blockade in acute myocardial infarction have not previously been published. In this controlled, double-blind study 20 patients were randomized to treatment with placebo or sotalol administered as a continuous infusion for 12 h. Programmed electrical stimulation was performed from the right atrium. After 60 min of infusion in the sotalol-treated patients (n = 10) there was a significant prolongation of sinus cycle length (+15%) and sinus node recovery time (+28%). The AV nodal effective refractory period was prolonged by 15% after 45 min of infusion. Variables reflecting myocardial repolarization, atrial effective refractory period and QT interval, were increased by 20% and 10%, respectively. In the placebo group, except at 12 h, there was a general pattern of slightly diminishing values for all measured variables. The electrophysiological changes in the sotalol-treated group could be explained by the combined Class II and III activities of this drug. The infusion of sotalol was well tolerated, and the anticipated electrophysiological and Class II and III antiarrhythmic effects were observed, despite the acute myocardial infarction.     

Magnesium infusion reduces the incidence of arrhythmias in acute myocardial infarction. A double-blind placebo-controlled study

In a double-blind placebo-controlled study, 130 patients with verified acute myocardial infarction were given magnesium or placebo treatment intravenously immediately upon admission to hospital. The incidence of arrhythmias requiring treatment during the initial week of hospitalization was registered. Serum magnesium concentrations were increased from 0.7 mmol/l to 1.3 mmol/l as a result of the magnesium infusions. This pharmacologically induced hypermagnesemia resulted in a reduction in the incidence of arrhythmias from 47% in the placebo group to 21% in the magnesium group (p = 0.003). In the magnesium-treated patients, increments in serum concentrations of magnesium and potassium correlated positively (r = 0.47, p less than 0.001). It is concluded that magnesium infusion in the postinfarct period reduces the incidence of supraventricular tachyarrhythmias, and possible pathophysiological mechanisms involved are discussed.     

Secondary prevention after myocardial infarction: Subgroup analysis of patients at risk in the norwegian timolol multicenter study

Timolol treatment after myocardial infarction is generally related to a significant reduction in both morality and reinfarction compared with placebo. Retrospective analyses of the timolol study are performed on subgroups of patients with a high placebo mortality. The present study shows that these patients are target groups for secondary prevention, as they benefit most from timolol treatment after myocardial infarction. In patients 65-75 years of age, the number of cardiac deaths and reinfarctions prevented by timolol treatment is twice as high as that of patients below 65 years of age. Timolol treatment is well tolerated in the older age group and the contraindications for timolol treatment are independent of age up to 75 years. The reduction in mortality and reinfarction is independent of heart size at baseline. However, in patients with cardiomegaly and compensated heart failure on treatment with digitalis and diuretics, timolol treatment may be of special importance because of the very high incidence of cardiac death in this group of patients. In patients with compensated heart failure on treatment with digitalis and diuretics, timolol treatment does not precipitate heart failure. Patients with stable diabetes mellitus basically behave like nondiabetic patients regarding inclusion rate, side effects, and timolol-related reduction in mortality and reinfarction. Decisions concerning secondary prevention with timolol should be independent of preinfarction and postinfarction angina. In conclusion, 70-80% of all the patients below 75 years of age surviving myocardial infarction, without contraindication to betablocker treatment, can be treated with timolol 10 mg twice daily to reduce mortality and reinfarction. In contrast to previous routines, secondary prevention with beta blockers should be especially directed to high-risk patients.     

老年急性心肌梗死患者溶栓疗效及安全性

目的　探讨老年急性心肌梗死 (AMI)患者接受静脉溶栓治疗的疗效及安全性。方法　回顾分析 3年内收治的AMI 643例中 30 2例接受静脉溶栓治疗的临床疗效。结果　 1 94例老年 (≥ 60岁 )组与 1 0 8例非老年组之间比较 ,其梗死相关血管 (IRA)再通率 (67.0 % ,73 .1 % )和出血及并发症率 (7.7% ,5 .65 % )均差异无显著性意义 (P >0 .0 5) ;所有接受溶栓治疗的AMI患者比不溶栓者的病死率 (7 0 % ,1 4 .7% )、中度以上心力衰竭发生率 (1 7.5 % ,30 .5 % )等明显减低 (P <0 .0 1 ) ;高龄 (≥ 80岁 )AMI2 9例中 ,8例溶栓者比不溶栓者的病死率低 1 6 .1 % ,中度以上心力衰竭低 32 .1 %。结论　AMI溶栓治疗在不同年龄组均安全、有效 ,而高龄患者得益更大     

Efficacy and safety of low-dose streptokinase plus desmopressin in acute myocardial infarction: A pilot study

In this pilot study the combined use of desmopressin, which releases tissue plasminogen activator from vascular endothelium, and a low dose of streptokinase as a new thrombolytic regimen for acute myocardial infarction is proposed. Eighteen patients with acute myocardial infarction were treated intravenously with 150,000 U (4 patients) or 250,000 U (14 patients) of streptokinase infused over 10 minutes, followed by 24 g of desmopressin infused over 5–10 minutes. Aspirin and beta-blockers were administered at admission, and heparin and oral anticoagulants were started at the end of the thrombolytic regimen. Hemostatic parameters were studied before and 30, 60, 120, and 240 minutes after starting thrombolytic therapy. Fifteen patients (83.3%) had evidence of clinical reperfusion. Angiography was performed with a mean delay of 8.8 hours (range 1.5–22 hours) from the start of thrombolytic therapy. Fourteen patients (77.8%) had patency of the infarct-related artery: 10 patients (55.6%) achieved TIMI grade 3, and 4 patients (22%) achieved TIMI grade 2. Two patients (one TIMI grade 1 and one TIMI grade 2) underwent coronary angioplasty. No patient died during the in-hospital period. At 18 months follow-up, all patients are alive. No major or minor bleeding was detected. The significant decline in plasma fibrinogen and in the euglobulin lysis time, and the increase in fibrinogen/fibrin degradation products, indicate a plasma lytic state. Crosslinked fibrin degradation products increased from 310±120 ng/ml to 670 ±310 ng/ml (p=0.009), suggesting that fibrin digestion occurred in vivo. This pilot study provides data supporting the feasibility and efficacy of a new and more economic thrombolytic treatment of acute myocardial infarction without hemorrhagic complications.     

大剂量氯吡格雷联合阿司匹林、尿激酶溶栓治疗急性ST段抬高型心肌梗死的疗效观察

目的:探讨大剂量氯吡格雷联合阿司匹林、尿激酶溶栓治疗急性ST段抬高型心肌梗死(STEMI)的临床疗效。方法:将70例STEMI患者随机等量分为两组,在尿激酶溶栓的基础上,试药组进行大剂量氯吡格雷联合阿司匹林治疗,对照组只进行常规阿司匹林治疗,治疗1周后观察比较两组的疗效和安全性。结果:两组复合终点事件的差异显著,试药组的近期疗效显著优于对照组(P0.05),两组的出血发生率无显著差异。结论:STEMI患者在应用阿司匹林,尿激酶治疗基础上加用大剂量氯吡格雷,可显著降低住院期间的病死率和心血管事件的发生。     

重组链激酶治疗急性心肌梗死的疗效和安全性

目的　探讨老年急性心肌梗死患者接受重组链激酶溶栓治疗的疗效和安全性。方法　 2 5 5例急性心肌梗死患者分为老年组 (15 7例 )和非老年组 (98例 ) ,分别对两组的临床疗效进行比较。结果　非老年组与老年组比较 ,其梗死相关血管再通率 (81.6 %vs79.0 % )、梗死后心绞痛 (8.2 %vs7.6 % )、再梗死 (2 .0 %vs3.2 % )、严重心律失常(11.2 %vs10 .8% )、心源性休克 (5 .1%vs5 .1% )、出血 (2 3.5 %vs2 1.7% )及其他并发症的发生率均无显著性差异(P >0 .0 5 )。结论　老年急性心肌梗死接受重组链激酶溶栓治疗是安全、有效的。     

NC100100, a new echo contrast agent for the assessment of myocardial perfusion--safety and comparison with technetium-99m sestamibi single-photon emission computed tomography in a randomized multicenter study

BACKGROUND AND HYPOTHESIS: Myocardial contrast echocardiography using second-generation agents has been proposed to study myocardial perfusion. A placebo-controlled, multicenter trial was conducted to evaluate the safety, optimal dose, and imaging mode for NC100100, a novel intravenous second-generation echo contrast agent, and to compare this technique with technetium-99m sestamibi (MIBI) single-photon emission computed tomography (SPECT). METHODS: In a placebo-controlled, multicenter trial, 203 patients with myocardial infarction > 5 days and < 1 year previously underwent rest SPECT and MCE. Fundamental and harmonic imaging modes combined with continuous and electrocardiogram-- (ECG) triggered intermittent imaging were used. Six dose groups (0.030, 0.100, and 0.300 microliter particles/kg body weight for fundamental imaging; and 0.006, 0.030, and 0.150 microliter particles/kg body weight for harmonic imaging) were tested. A saline group was also included. Safety was followed for 72 h after contrast injection. Myocardial perfusion by MCE was compared with myocardial rest perfusion imaging using MIBI as a tracer. RESULTS: NC100100 was well tolerated. No serious adverse events or deaths occurred. No clinically relevant changes in vital signs, laboratory parameters, and ECG recordings were noted. There was no significant difference between adverse events in the NC100100 (25.7%) and in the placebo group (17.9%, p = 0.3). Intermittent harmonic imaging using the intermediate dose was superior to all other modalities, allowing the assessment of perfusion in 76% of all segments. Eighty segments (96%) with normal perfusion by SPECT imaging also showed myocardial perfusion with MCE. However, a substantial percentage of segments (61-80%) with perfusion defects by SPECT imaging also showed opacification by MCE. This resulted in an overall agreement of 66-81% and a high specificity (80-96%), but in low sensitivity (20-39%) of MCE for the detection of perfusion defects. CONCLUSION: NC100100 is safe in patients with myocardial infarction. Intermittent harmonic imaging with a dose of 0.03 microliter particles/kg body weight can be proposed as the best imaging protocol. Myocardial contrast echocardiography with NC 100100 provides perfusion information in approximately 76% of segments and results in myocardial opacification in the vast majority of segments with normal perfusion as assessed by SPECT. Although the discrepancies between MCE and SPECT with regard to the definition of perfusion defects requires further investigation, MCE with NC 100100 is a promising technique for the noninvasive assessment of myocardial perfusion.     

老年急性心肌梗死溶栓治疗的疗效与安全性研究

目的　研究老年人急性心肌梗死 (AMI)溶栓治疗的疗效及安全性。　 方法　溶栓治疗组 15 8例 ,采用尿激酶 (UK) ( 1 5～ 2 0 )× 10 4 U·kg-1,总剂量控制在 15 0× 10 4 U之内加入生理盐水 10 0ml内 ,30min静滴完毕 ,此后低分子肝素 75 0 0U ,皮下注射 ,2次·d-1,连用 5～ 7d ,并按规定时间查心电图和心肌酶谱。对照组 186例 ,仅给对症处理及GIK液等治疗。 2组均给予阿司匹林 0 3g ,1次·d-1,5～ 7d后改 5 0～ 75mg·d-1。　 结果　住院期间的病死率 :溶栓组 6 9% ,对照组 18 8% ,P >0 0 5 ;再通组 3 2 % ,未通组 12 5 % ,P >0 0 5。总的心血管事件及需经皮冠状动脉腔内成形术 (PTCA)治疗的病例 :溶栓组 44 3 % ,对照组 6 2 4% ,P <0 0 5。出血的发生率 :溶栓组 32 3% ,对照组 2 7% ,P <0 0 1,但无 1例发生致命性脑出血。　 结论 　老年人AMI溶栓治疗有一定风险 ,但利大于弊     

Two-year follow-up data from the STEPP-AMI study: A prospective,observational, multicenter study comparing tenecteplase-facilitated PCI versus primary PCI in Indian patients with STEMI

BackgroundA pharmacoinvasive strategy may alleviate the logistical and geographical barriers in timely reperfusion of ST-segment elevation myocardial infarction (STEMI), especially in a developing country like India.AimTo assess the safety and efficacy of pharmacoinvasive strategy versus primary PCI in STEMI patients at 2 years.MethodsPatients enrolled in STEPP-AMI, an observational, multicenter, prospective study of 200 patients presenting with STEMI, were followed up for 2 years. Group ‘A’ comprised of patients with pharmacoinvasive strategy (n = 45), and patients who underwent primary PCI (n = 155) formed group ‘B’. Primary endpoint was composite of death, cardiogenic shock, reinfarction, repeat revascularization of the culprit artery, or congestive heart failure at 30 days, with follow-up till 2 years.ResultsThe primary endpoint occurred in 11.1% and 17.8% in group A and in 3.9% and 13.6% in group B, at 30 days and 2 years, respectively (p = 0.07, RR = 2.87; 95% CI: 0.92–8.97 at 30 days and p = 0.47, RR = 1.31; 95% CI: 0.62–2.76). There was no difference in bleeding risk between groups, 2.2% in group A and 0.6% in group B (‘p’ = 0.4). The infarct-related artery patency varied at angiogram; it was 82.2% in arm A and 22.6% in arm B (‘p’ < 0.001). In group A, failed fibrinolysis occurred in 12.1%.ConclusionA pharmacoinvasive strategy resulted in outcomes that were comparable with primary PCI at 2 years, suggesting it might be a viable option in India. Larger studies are required to confirm these findings.     

HTUPA as a new thrombolytic agent for acute myocardial infarction: A multicenter,randomized study

Background

It is necessary to develop a new thrombolytic agent which can be used by a single bolus at first aid sites to decrease the time to reperfusion in clinical practice. HTUPA, a genetically engineered new thrombolytic with a longer half-life, is well qualified. We aim to compare the thrombolytic efficacy and safety of human tissue urokinase type plasminogen activator (HTUPA) to recombinant tissue plasminogen activator (rt-PA) in Chinese patients with acute myocardial infarction (AMI).

Methods

AMI patients (n = 221) were randomized to rt-PA (a standard protocol) or HTUPA (25 mg bolus) treatment groups. All patients also received oral aspirin and intravenous heparin. Coronary angiography was performed 90 min after therapy initiation to determine infarct-related coronary artery (IRA) patency. Clinical outcomes and changes of clotting variables, heart rate, blood pressure, left ventricular ejection fraction (LVEF), and electrocardiogram were evaluated.

Results

Patent IRA [thrombolysis in myocardial infarction (TIMI) grade 2 or 3] was observed in 77% of HTUPA-treated patients, compared to 76% of rt-PA-treated patients (P = 0.76). TIMI grade 3 patency rates were 52% and 44% in the HTUPA and rt-PA groups, respectively (P = 0.37). The total patency rate was 77% (86/111 patients) in the HTUPA group and 73% (80/110 patients) in the rt-PA group (P = 0.41). Adverse events were infrequent in both groups, and no significant differences were detected in mortality, re-occlusion rate, revascularization rate, adverse effects, clotting index, LVEF, or electrocardiogram between the two groups.

Conclusions

Intravenous HTUPA had a safe and efficacious profile as good as rt-PA in patients with AMI.     

Efficacy and safety of tacrolimus for lupus nephritis: a placebo-controlled double-blind multicenter study

We evaluated the efficacy and safety of tacrolimus in patients receiving glucocorticoid therapy for lupus nephritis. Patients with persistent nephritis were randomized to receive 28 weeks of double-blind treatment with tacrolimus (3 mg/day) or placebo. The primary endpoint was the change in the lupus nephritis disease activity index (LNDAI) calculated from scores for daily urinary protein excretion, urinary red cells, serum creatinine, anti-double-stranded DNA antibody, and serum complement. Statistical analysis was performed using the full analysis set. The LNDAI was decreased by 32.9 ± 31.0% (mean ± SD) in the tacrolimus group (n = 28) and was increased by 2.3 ± 38.2% in the placebo group (n = 35) at final evaluation. There was significant improvement in the tacrolimus group. Daily urinary protein excretion showed a significant decrease in the tacrolimus group (p < 0.001). The complement (C3) level showed a significant increase in the tacrolimus group (p = 0.001). Treatment-related adverse events occurred in 92.9% of the tacrolimus group and 80.0% of the placebo group, but the difference was not significant. In patients on glucocorticoid therapy for lupus nephritis, addition of tacrolimus to basal therapy achieved significant improvement compared with placebo. Tacrolimus may therefore be a useful alternative treatment for lupus nephritis.     

Efficacy and safety of tacrolimus for lupus nephritis: a placebo-controlled double-blind multicenter study

Abstract

We evaluated the efficacy and safety of tacrolimus in patients receiving glucocorticoid therapy for lupus nephritis. Patients with persistent nephritis were randomized to receive 28 weeks of double-blind treatment with tacrolimus (3 mg/day) or placebo. The primary endpoint was the change in the lupus nephritis disease activity index (LNDAI) calculated from scores for daily urinary protein excretion, urinary red cells, serum creatinine, anti-double-stranded DNA antibody, and serum complement. Statistical analysis was performed using the full analysis set. The LNDAI was decreased by 32.9 ± 31.0% (mean ± SD) in the tacrolimus group (n = 28) and was increased by 2.3 ± 38.2% in the placebo group (n = 35) at final evaluation. There was significant improvement in the tacrolimus group. Daily urinary protein excretion showed a significant decrease in the tacrolimus group (p < 0.001). The complement (C3) level showed a significant increase in the tacrolimus group (p = 0.001). Treatment-related adverse events occurred in 92.9% of the tacrolimus group and 80.0% of the placebo group, but the difference was not significant. In patients on glucocorticoid therapy for lupus nephritis, addition of tacrolimus to basal therapy achieved significant improvement compared with placebo. Tacrolimus may therefore be a useful alternative treatment for lupus nephritis.     

Dose-ranging study with a new two-chain rt-PA in patients with acute myocardial infarction: A multicenter trial

Tissue-type plasminogen activator (t-PA) derived from a melanoma cell line was first used in patients with acute myocardial infarction in the early 1980s. Recombinant DNA technology then allowed production of large amounts of t-PA. The TIMI-I trial used a two-chain recombinant (rt-PA) product. A predominantly single-chain rt-PA (alteplase) was used in the majority of the TIMI II trial. The present study used a different form of two-chain rt-PA (duteplase) to determine the effective dose for thrombolysis at 60 min, and to evaluate time to reperfusion, reocclusion at 72-96 h, coagulation profiles, and bleeding events. Duteplase was given intravenously to 75 patients a mean of 3.8±1 h after the onset of myocardial infarction. Following angiography demonstrating coronary occlusion, 23 patients received a low dose of duteplase [0.16-0.29 million international units per kilogram (MIU/kg)] over 60 min followed by a 5-h infusion in conjunction with heparin, 25 patients received a middle dose (0.30-0.41 MIU/kg) and 23 patients received a high dose (0.43-0.74 MIU/kg). Angiography was then performed every 15 min × 4. Progressive recanalization occurred over 60 min (median 45 min) with an overall success rate of 59% (mean 60-min dose: 0.37 MIU/kg). No dose-response relationship was observed. The reocclusion rate was 9% at 72-96 h. Reductions in fibrinogen and plasminogen correlated with dose, but clinical events did not. These data are important because this form of rt-PA was employed in the recently reported ISIS-3 trial and the mean dose of duteplase in the present trial is the same as the 60-min dose employed in ISIS-3.