Intravenous versus intracoronary streptokinase for acute transmural myocardial infarction

In order to compare the thrombolytic efficacy of selective versus systemic administration of streptokinase, we gave this drug by either the intracoronary or intravenous routes to 25 patients during the first 6 hours of acute myocardial infarction. All patients had total occlusion of the infarct-related vessel, unresponsive to intracoronary nitroglycerin. Twelve patients received intravenous streptokinase and 13 received intracoronary administration of the drug. Angiograms were taken prior to and during streptokinase administration. Reopening was achieved in 11 of 13 intracoronary patients and 8 of 12 intravenous patients (P = Ns). Time to reopening was longer (54 minutes) in the intravenous patients than in the intracoronary patients (26 minutes) (P < 0.05). In this study, intravenous streptokinase reopened infarct-related vessels nearly as often as intracoronary streptokinase, but it took longer. Given the limited access and time to prepare for intracoronary infusion and the ease of intravenous administration, further study of intravenous streptokinase is justified.     

Intravenous streptokinase in acute myocardial infarction

Intravenous (IV) fibrinolytic therapy, a recent area of research, has a great deal of applicability in emergency medicine. We report our experience with 30 patients treated with this method. Thirty consecutive patients in the early stages of acute evolving myocardial infarction (AMI) were assigned to receive high-dose IV streptokinase, 1.5 million units over a 30-minute period. Patients presented to the treating hospital at a mean time of 1.21 +/- 1.08 hours, and treatment commenced at a mean time of 2.77 +/- 1.31 hours after the onset of symptoms. Using standard clinical criteria, 86.7% (n = 26) of the patients reperfused initially. Two, however, reoccluded within the first 48 hours, and their clinical symptoms of myocardial infarction reappeared. By clinical observation 80% (n = 24) of the patients reperfused, and myocardial salvage was observed. Twenty-four patients with clinical reperfusion and one additional patient had patency of the affected artery, yielding a reperfusion rate of 83.3% (n = 25) as judged by angiography within one week of AMI. Both patients who had reoccluded clinically also were found to be occluded on angiography. Clinical and angiographic methods yield very similar results for the judgment of reperfusion (80% vs 83%, respectively, with no significant difference, P not significant). The results of our study tend to confirm the efficacy of IV streptokinase as a valuable management tool for early myocardial infarction.     

Dose of urokinase for intracoronary thrombolysis in patients with acute myocardial infarction

Intracoronary thrombolysis is a logical therapeutic method and one of the challenging new treatments of acute myocardial infarction. However, a wide dose range of urokinase has been reported, and the optimal dose has not yet been established. In this study the fibrinolytic activity in patients with recanalized coronary arteries was compared with that in those with nonrecanalized arteries. The mean doses of urokinase in the recanalized and non-recanalized groups were 910,700 +/- 161,730 international units (IU) and 1,008,000 +/- 151,800 IU, respectively. The fibrinolytic activity was measured with alpha 2-plasmin inhibitor, alpha 2-macroglobulin, fibrinogen, plasminogen, and fibrin degradation products. No significant difference was observed in the fibrinolytic activity between the recanalized and nonrecanalized groups. Because the fibrinolytic activity in the two groups was thought to be activated sufficiently and to a similar degree, it appears that 1,000,000 IU of urokinase is adequate for intracoronary thrombolysis and larger doses cannot be expected to result in a higher rate of recanalization.     

不同溶栓药物和剂量治疗急性心肌梗塞239例对比分析

２３９例急性心肌梗塞（ＡＭＩ）患者接受溶栓治疗，其中采用日本尿激酶（ＵＫ）９６万Ｕ３５例，１５０万Ｕ５５例；国产ＵＫ９６万Ｕ１５例，１５０万Ｕ５３例；德国链激酶（ＳＫ）１５０万Ｕ６６例；国产重组链激酶（ｒＳＫ）１５０万Ｕ１５例。对不同剂量及不同溶栓剂的疗效与安全性进行对比分析发现：１９９２年前国产ＵＫ９６万Ｕ比日本进口ＵＫ９６万Ｕ血管再通率低（２０．０％ｖｓ５１．４％Ｐ＜０．０１）。１９９２年后国产ＵＫ剂量增至１５０万Ｕ，血管再通率显著提高（５６．６％ｖｓ２０．０％Ｐ＜０．０１），与进口ＵＫ１５０万Ｕ的疗效与安全性相近（Ｐ＞０．０５）；国产ｒＳＫ１５０万Ｕ与进口ＳＫ１５０万Ｕ的血管再通率相似（７３．３％ｖｓ６５．２％Ｐ＞０．０５）；且比国产ＵＫ１５０万Ｕ的血管再通率明显提高（７３．３％ｖｓ５６．６％Ｐ＜０．０５），虽然ｒＳＫ轻度出血高于ＵＫ（２６．７％ｖｓ９．４％Ｐ＜０．０１），偶有低血压发生，但不影响疗效。国产ｒＳＫ与ＵＫ比进口ＳＫ和ＵＫ价格低２～４倍。因此认为，国产ｒＳＫ和ＵＫ是较为有效、安全、价廉且适合我国国情的溶栓药物。     

Randomized factorial trial of high-dose intravenous streptokinase, of oral aspirin and of intravenous heparin in acute myocardial infarction

619 patients with suspected acute myocardial infarction (MI)were randomized to receive either a high-dose short-term intravenousinfusion of streptokinase (1.5 MU over one hour) or placebo.Using a '2 x 2 x 2 factorial' design, patients were also randomizedto receive either oral aspirin (325 mg on alternate days for28 days) or placebo and separately randomized to receive eitherintravenous heparin (1000 1U h-1 for 48 hours) or no heparin.Streptokinase (SK) was associated with a nonsignificant (NS)increase in non-fatal reinfarc–tion (3.9% SKvs 2.9% placebo)and decrease in mortality (7.5%vs9.7% in hospital plus 6.1%vs8.7% after discharge). After SK, there were significantly fewerstrokes (0.5% vs 2.4%; 2P<0.05), but significantly more minoradverse events (e.g. hypotension and bradycardial, allergies,bruises or minor bleeds, nausea). Aspirin was associated withfewer non-fatal reinfarctions (3.2% aspirin vs 39% placebo;NS), deaths (in hospital: 61% vs 10.5%; 2P<0.05, and afterdischarge: 7.0% vs 6.9%; NS), and strokes (0.3% vs 2.0%; NS).Heparin was associated with a decrease in reinfarction (2.2%heparin vs 4.9% no heparin; NS), though not in mortality (inhospital: 8.0% vs 8.5%; NS, and after discharge: 7.0% vs 6.9%;NS), and with a trend towards more strokes (1.6% vs 0.7%; NS)and more bruising and bleeding (14% vs 12%; NS). To assess morereliability the effects of aspirin and of this SK regimen onmortality, about 400 hospitals worldwide are now collaboratingin a large (about 20 000 patients planned ) randomized trial( ISIS-2). for which the present study was a pilot.     

急诊介入与溶栓治疗急性心肌梗死患者疗效对比分析

目的比较经皮冠状动脉介入治疗与静脉溶栓治疗急性心肌梗死的疗效。方法将60例急性心肌梗死患者随机分为介入组（30例）和静脉组（30例）,介入组采用对梗死相关动脉行经皮冠状动脉腔内成形术（PTCA）＋支架术治疗,静脉组按照中华心血管病杂志编辑委员会制定的溶栓方案进行治疗,比较两组患者ST回落情况、再通率、病死率、心血管事件发生率和心功能情况。结果介入组与静脉组比较,ST回落明显迅速,病死率、再通率、心血管事件发生率及心功能改善均明显优于静脉组。结论采取经皮冠状动脉介入治疗急性心肌梗死,能及时有效地开通梗死相关动脉,挽救濒死的心肌,改善心功能,降低病死率,可作为急性心肌梗死的首选治疗方法。     

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。     

Randomized comparison of enoxaparin with unfractionated heparin following fibrinolytic therapy for acute myocardial infarction.

AIMS: To compare the efficacy and safety of low molecular weight heparin with unfractionated heparin following fibrinolytic therapy for acute myocardial infarction. METHODS AND RESULTS: Three-hundred patients receiving fibrinolytic therapy following acute myocardial infarction were randomly assigned to low molecular weight heparin as enoxaparin (40 mg intravenous bolus, then 40 mg subcutaneously every 8 h, n=149) or unfractionated heparin (5000 U intravenous bolus, then 30 000 U. 24 h(-1), adjusted to an activated partial thromboplastin time 2-2.5x normal, n=151) for 4 days in conjunction with routine therapy. Clinical and therapeutic variables were analysed, in addition to use of enoxaparin or unfractionated heparin, to determine independent predictors of the 90-day composite triple end-point (death, non-fatal reinfarction, or readmission with unstable angina). The triple end-point occurred more frequently in patients receiving unfractionated heparin rather than enoxaparin (36% vs. 26%; P=0.04). Logistic regression modelling of baseline and clinical variables identified the only independent risk factors for recurrent events as left ventricular failure, hypertension, and use of unfractionated heparin rather than enoxaparin. There was no difference in major haemorrhage between those receiving enoxaparin (3%) and unfractionated heparin (4%). CONCLUSION: Use of enoxaparin compared with unfractionated heparin in patients receiving fibrinolytic therapy for acute myocardial infarction was associated with fewer recurrent cardiac events at 90 days. This benefit was independent of other important clinical and therapeutic factors.     

Anti-thrombotic, anti-platelet and fibrinolytic therapy: current management of acute myocardial infarction

Significant advances in the treatment of patients with acute myocardial infarction (MI) have been obtained in recent times. In particular, thrombolytic therapy has been shown to preserve ventricular function and improve survival in patients with acute MI. Therapies now include third-generation thrombolytic agents, percutaneous transluminal coronary angioplasty (PTCA) and intracoronary stenting, and new anti-thrombotic therapies including anti-platelet treatment with glycoprotein (GP) IIb/IIIa inhibition and direct anti-thrombin agents. This review will focus on the use of GP IIb/IIIa antagonists and thrombin inhibitors as adjunctive therapies to thrombolytic treatment of patients with acute MI.     

链激酶,尿激酶静脉溶栓对凝血和纤溶系统的影响

尿激酶（ＵＫ）和链激酶（ＳＫ）同属第一代溶栓剂，二者均无“纤维蛋白选择性”，本研究目的在于比较ＳＫ和ＵＫ对凝血和纤溶系统的影响及其与临床的关系。静脉溶栓治疗急性心肌梗塞１１１例，其中５５例使用ＳＫ（１５０万单位／例），５６例使用ＵＫ（１．７－２．３万单位／ｋｇ体重，平均１５３．２５万单位／例），于溶栓前、溶栓后２、６、１２、２４小时、第３天、第７天分别测定血浆纤溶酶原激活物（ＰＡ）、纤溶酶原激活物抑制物（ＰＡＩ）、及纤溶酶原（ＰＬＧ）活性，并测定纤维蛋白原（ＦＧ）浓度、激活的试管法凝血时间（ＡＣＴ）。结果显示：ＳＫ引起的凝血和纤溶系统变化均比ＵＫ明显，特征为：在溶栓后２～６小时有较高的ＰＡ活性和较低的ＰＡＩ活性；溶栓后２小时较长的凝血时间；较低的纤维蛋白原浓度从２小时持续到第７天，上述差异均有极显著意义。本文结果提示ＳＫ对凝血和纤溶系统的影响比ＵＫ强烈而持久，二者在血液学特征上的差异与临床疗效及使用抗凝剂等问题可能有一定的关系。     

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。     

国产重组链激酶急性心肌梗塞溶栓治疗临床试验

观察国产重组链激酶（ｒ－ＳＫ）在急性心肌梗塞（ＡＭＩ）静脉溶栓治疗中的临床疗效和不良反应，对其安全性和疗效作出评价。试验分为随机单盲对照试验组，即ｒ－ＳＫ（上海医科大学研制）５１例，链激酶（ＳＫ，德国赫斯特药厂产品）５１例和ｒ－ＳＫ开放组７１例。所有病例均符合入选和不入选标准，予ｒ－ＳＫ或ＳＫ各１５０万Ｕ于６０分钟静脉注入，观察血管再通的临床指标，过敏反应及出血并发症等。在随机单盲对照试验组中，５１例ｒ－ＳＫ的血管再通率（８０．４％）与ＳＫ（７４．５％）相近。总的１２２例ｒ－ＳＫ患者的血管再通率为７７．１％。ｒ－ＳＫ的不良反应中，寒颤发生率为４．１％，低血压为５．７％，出血发生率为１６．４％，均表现为皮肤，胃肠道或泌尿道的轻微出血，一般不需处理自行消失。由于ｒ－ＳＫ静脉溶栓治疗血管再通率高，过敏反应及低血压的发生率低，程度轻，出血并发症少，认为国产ｒ－ＳＫ为一安全有效的溶栓剂。     

Serum sickness complicating intravenous streptokinase therapy in acute myocardial infarction

A case of delayed serum sickness with transient renal impairmentis described in a patient who received early high dose intravenousstreptokinase following acute myocardial infarction. Reviewof the literature suggests that serum sickness after streptokinasemay occur independently of the dose or route of administration,and could potentially complicate intracoronary streptokinasetherapy.     

The effect of streptokinase neutralizing antibodies on fibrinolytic activity and reperfusion following streptokinase treatment in acute myocardial infarction

Abstract. Nilsson JB, Nilsson TK, Jansson J‐H, Boman K, Söderberg S, Näslund U (Heart Centre, University Hospital, Umeå; Örebro Medical Centre, Örebro; Skellefteå Hospital, Skellefteå; Sweden). The effect of streptokinase neutralizing antibodies on fibrinolytic activity and reperfusion following streptokinase treatment in acute myocardial infarction. J Intern Med 2002; 252: 405–411. Objectives. To evaluate tissue plasminogen activator (tPA) activity as a measure of fibrinolytic response to treatment with streptokinase (SK) and to relate this to the effect of pretreatment SK antibodies and to successful reperfusion assessed by continuous computerized vectorcardiography (VCG). Setting. Umeå University Hospital. Subjects. A total of 104 patients with acute myocardial infarction (AMI) treated with SK and no history of previous SK treatment were studied. The tPA activity was measured 4 h after the start of treatment. The effect of pre‐existing neutralizing antibodies to SK was analysed with a functional assay in pretreatment samples. Reperfusion was evaluated with VCG. Main outcome measures. Successful reperfusion. Results. Fifty‐five patients (53%) were classified as successfully reperfused. The risk for failed reperfusion was calculated in logistic regression models. In a univariate model, a borderline significant increase in the risk of failed reperfusion was observed in intermediate levels of SK neutralizing antibodies, but not in the highest levels. In a multivariate model, only high tPA activity, >25 U mL^?1, at 4 h (OR 0.17; 95% CI: 0.06–0.51) was associated with a higher rate of reperfusion whilst longer time to treatment (OR 1.17; 95% CI: 1.02–1.35) was associated with a higher risk of failed reperfusion. There was no significant correlation between neutralizing antibodies to SK and tPA activity at 4 h. Conclusion. The SK treatment of AMI induced high levels of tPA activity which were associated with successful reperfusion. The effect of pre‐existing SK antibodies had no significant influence on reperfusion and were not correlated to the fibrinolytic activity obtained.     

我国消化性溃疡防治性研究随机对照试验的现状分析

目的 了解我国消化性溃疡及消化系疾病防治性研究随机对照试验（RCT）的现状,及能否为临床提供可靠的研究依据。方法 对我国可能刊登上述RCT的6种中文杂志进行人工逐篇查阅,并根据国际标准对消化性溃疡RCT进行分析。结果 查阅314期,共含治疗性文章2421篇,检索出RCT395篇,并对消化性溃疡RCT报告106篇进行了分析。结论 我国消化性溃疡及消化系疾病的防治性研究RCT的数量和质量,还不能满足临床实践的需要。     

Mortality, reinfarction, left ventricular ejection fraction and costs following reperfusion therapies for acute mvocardial infarction

The comparative efficacy of thrombolytic drugs and primary angioplastyfor acute myocardial infarction have recently been studied,but long-term follow-up data have not yet been reported. Weconducted a randomized trial involving 301 patients with acutemyocardial infarction; 152 patients were randomized to primaryangioplasty and 149 to intravenous streptokinase. Left ventricularfunction was assessed with a radionuclide technique both athospital discharge and at the end of the follow-up period. Follow-updata were collected after a mean (± SD) of 31 ±9 months. Total medical costs were calculated. At the end ofthe follow-up period, 5% of the angioplasty patients had diedfrom a cardiac cause compared to 11% of the patients randomizedto intravenous streptokinase, P=0·031. Cardiac deathor a non-fatal reinfarction occurred in 7% of angioplasty patientscompared to 28% of streptokinase patients, P0·001. Therewas a sustained benefit of angioplasty compared to streptokinaseon left ventricular function. The total medical costs in thetwo groups were similar. Coronary anatomy (patency and singleor multivessel disease), infarct location and previous myocardialinfarction were important determinants of clinical outcome andcosts. After 31±9 months of follow-up, primary angioplasty comparedto intravenous streptokinase results in a lower rate of cardiacdeath and reinfarction, a better left ventricular ejection fraction,and no increase in total medical costs. (Eur Heart J 1996; 17: 382–387)     

Effect of thrombolytic therapy on exercise response during early recovery from acute myocardial infarction: a placebo controlled study.

Several studies have shown that infarct size is reduced following thrombolytic treatment in patients with acute myocardial infarction. Exercise test variables, such as an impaired heart rate response during exercise, are known to be related to left ventricular function and patient prognosis following acute myocardial infarction. The present study was performed to compare exercise test variables in acute myocardial infarction patients following either intravenous thrombolysis or placebo. Symptom-limited bicycle ergometer tests, carried out 1-2 weeks from the infarction, were performed in 85 patients randomized to intravenous streptokinase (N = 41) or placebo (N = 44) given within 12 h from onset of symptoms. At rest heart rate, systolic blood pressure and rate-pressure product were similar in the two groups. At maximum workload the streptokinase treated patients had a higher median maximal heart rate than controls (136 vs. 126 b.min-1, P less than 0.01) but only a trend towards higher systolic blood pressure was seen (175 vs. 163 mmHg, P = 0.09). Rate-pressure product at maximal exercise was 23,620 vs. 20,100 mmHg.b.min-1 respectively, (P less than 0.01). Total exercise time, ST-segment deviation, occurrence of angina pectoris and left ventricular ejection fraction were similar in the two groups. The trend towards an increased heart rate at maximum workload in streptokinase-treated patients was seen at all levels of left ventricular ejection fraction, and at all levels of exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Streptokinase antibodies inhibit reperfusion during thrombolytic therapy with streptokinase in acute myocardial infarction

OBJECTIVES: To evaluate the influence of pretreatment IgG against streptokinase on the outcome of streptokinase treatment in acute myocardial infarction. SETTING: Coronary care unit. DESIGN: From 88 patients admitted to the coronary care unit due to chest pain, blood samples were taken for determination of the pre-existing titre of antibodies against streptokinase. The patients were treated and monitored according to standard protocols. Fifty of the patients received thrombolytic therapy with streptokinase due to acute myocardial infarction and were monitored with continuous dynamic vectorcardiography, making possible the continuous analysis of ST- and QRS-vector changes and determination of the event of reperfusion. None of these 50 patients had been given streptokinase therapy previously. RESULTS: According to the vectorcardiographic criteria 21(42%) patients had signs of early (within 2 h) reperfusion after streptokinase therapy. These patients had lower pre-existing antibody titres than patients without signs of reperfusion (mean values 0.20 and 0.45 arbitrary units, P = 0.01). None of the patients with a titre higher than 0.50 arbitrary units (nine patients) had signs of early reperfusion. Of the 41 patients with a titre lower than 0.50 arbitrary units 52.5% had signs of early reperfusion. CONCLUSION: The present investigation indicates that pre-existing streptokinase antibodies play an important role in reperfusion failure during thrombolytic therapy with streptokinase in acute myocardial infarction. Therefore, the determination of streptokinase antibodies may differentiate between those patients who may benefit from streptokinase treatment and those who should be treated with some other regime.