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K L Neuhaus

Publications and source records attributed to K L Neuhaus.

At least 55 records · Page 3Linked to original sources
PubMed1996

Thrombolysis and mechanical intervention following myocardial infarction.

In concept, mechanical interventions are attractive options for treating acute myocardial infarction with or without preceding thrombolysis: rapid reperfusion of the infarct-related artery can be achieved in the vast majority of cases, and the underlying coronary lesion is treated at the same time. Various strategies have been extensively investigated. When performed in specialized centres, direct percutaneous transluminal coronary angioplasty (PTCA) without prior thrombolysis appears to improve the outcome more than conventional thrombolysis. Whether this also holds true for the diverse range of hospitals remains unknown. Routine PTCA after thrombolysis did not show any benefit over thrombolysis alone. Rescue PTCA after failed thrombolysis is probably beneficial. Currently, only limited experience exists with other mechanical interventions, including intra-aortic balloon pumping, thrombectomy with special new devices, or stent insertion, which need further investigation before they can be recommended for routine use in acute myocardial infarction.

Angioplasty, Balloon, Coronary↗
PubMed1996

Recombinant hirudin (HBW 023) produces stable anticoagulation unaffected by circadian variation in patients with thrombolysis for acute myocardial infarction.

BACKGROUND: Circadian variations have been described for a number of haemostatic and physiological factors, all of which might predispose towards clotting in the late morning. The anticoagulation effect of heparin has been shown to respond in a circadian manner, resulting in minimal prolongation of the activated partial thromboplastin time (aPTT) in the morning. METHODS: Recombinant hirudin (HBW 023) given as a bolus of 0.07, 0.1, 0.2 or 0.4 mg.kg-1 followed by an infusion of 0.05, 0.06, 0.1 or 0.15 mg.kg-1 over 48 h was used as conjunctive therapy to thrombolysis with front-loaded recombinant tissue-type plasminogen activator (100 mg.90 min-1) in 40 patients with acute myocardial infarction. APTT, activated clotting time and free hirudin plasma levels were determined at baseline and at 8, 12, 16, 20, 24, 32, 40 and 48 h. RESULTS: The prolongation of aPTT and activated clotting time was dose-dependent and stable. In 82.5% of the patients, aPTT values were ranged between the highest and the lowest aPTT of < 30 s. When the results were divided into four time intervals (0000-0600, 0600-1200, 1200-1800, 1800-2400) neither in the individual patients nor in the mean values of the four different dose groups was any significant circadian variation in aPTT or activated clotting time prolongation observed. The pharmacokinetic studies of free hirudin plasma levels revealed no circadian rhythm either. All but one patient (97.5%) had a patent vessel (TIMI grade 2/3) at the end of the hirudin infusion. CONCLUSIONS: Recombinant hirudin, in contrast to heparin, does not show any circadian variation in its anticoagulation effect. This might, in part, explain the more stable and predictable anticoagulation achieved by hirudin, which is associated with a reduced rate of reocclusions after thrombolysis.

Adult↗
PubMed1995

[Cardioversion in atrial fibrillation. Results and complications in 1,152 prospective patients. Study Group of the Working Society of Leading Cardiologic Hospital Physicians].

BACKGROUND: Pharmacological and direct-current cardioversion of atrial fibrillation are often performed interventions. Little is known about results and complications of cardioversion in daily practise. PATIENTS AND METHODS: Demographic, procedural and outcome data from patients with cardioversion of atrial fibrillation were collected in a prospective, multicenter registry of 61 hospitals. RESULTS: Between July 1994 and December 1994 1152 patients with a mean age of 64 +/- 11 years were registered on an intention-to-treat basis. 62% were male. The most prevalent underlying disorders were coronary artery disease (34.7%), valvular heart disease (18.1%), and cardiomyopathy (6.9%). 16.4% of patients had lone atrial fibrillation. New onset atrial fibrillation was reported in 21%, paroxysmal in 32% and chronic in 47% of patients. The mean duration of atrial fibrillation was 7 +/- 26 weeks (range 1 day to 7 years, median 5 days). In 3.8% of patients no cardioversion attempt was made and follow-up was not possible in another 5.5%. 19.2% of patients cardioverted spontaneously. Direct current cardioversion was attempted in 39.7% and pharmacological cardioversion in 31.8% of patients. Cardioversion was successful (sinus rhythm at discharge) in 96.4% of spontaneous cardioversion, in 73.1% of direct current cardioversion and in 84.4% of pharmacological cardioversion. Success of cardioversion was significantly related to duration of atrial fibrillation, NYHA functional class and left atrial diameter (p < 0.001). In 55 (4.8%) cases complications were reported of which 14 were fatal. Five cases of sudden death occurred, all of which were related to quinidine therapy for pharmacological cardioversion. Five cases of embolism were reported. Two were not associated with cardioversion attempts and 3 occurred within 24 hours after successful direct current cardioversion. Two of these patients were effectively anticoagulated at the time of cardioversion. A total of only 62% of patients with atrial fibrillation of more than 48 hours duration were anticoagulated for cardioversion with coumadine or i.v. heparin. CONCLUSIONS: The main risks of cardioversion are fatal proarrhythmic events in pharmacological attempts to restore sinus rhythm. The risk of embolism is despite low rates of effective anticoagulation low.

Aged↗
PubMed1995

Frequency of "optimal anticoagulation" for acute myocardial infarction after thrombolysis with front-loaded recombinant tissue-type plasminogen activator and conjunctive therapy with recombinant hirudin (HBW 023). ALKK Study Group.

This retrospective analysis reviewed 183 patients with acute myocardial infarction who were given front-loaded recombinant tissue-type plasminogen activator (rt-PA) and r-hirudin (HBW 023) in 1 of 4 dose groups (bolus dose of 0.07, 0.1, 0.2, or 0.4 mg/kg, followed by an infusion of 0.05, 0.06, 0.1, or 0.15 mg/kg/hour over 48 hours). Activated partial thromboplastin time (aPTT) levels were determined at baseline and at 4, 8, 12, 16, 20, 24, 32, 40, and 48 hours. Of the 178 patients with r-hirudin treatment for > or = 12 hours, anticoagulation was optimal in 55.1% (all aPTTs > 2 x baseline), suboptimal in 33.7% (lowest aPTT > 1.5 but < 2 x baseline), and inadequate in 11.2% (> or = 1 aPTT but < 1.5 x baseline). Optimal anticoagulation was observed more frequently in the higher dose groups (dose 1, 15%; dose 2, 44.4%; dose 3, 63.4%; dose 4, 73.4%; p for trend < 0.0001). Patency (according to Thrombolysis in Myocardial Infarction trial grade 2 or 3) of the infarct artery after 36 to 48 hours was higher in the group with optimal anticoagulation compared with those with suboptimal or inadequate anticoagulation: 97.9%, 88.4%, and 85%, respectively (p = 0.03 optimal vs suboptimal or inadequate anticoagulation). In conclusion, r-hirudin in a dose of 0.1 or 0.15 mg/kg/hour achieves an optimal anticoagulation in about 63% or 74% of patients, which is associated with an enhanced patency 24 to 48 hours after rt-PA. A subsequent study revealed that this effective anticoagulation may be accompanied by an increased risk of severe bleeding complications after thrombolysis.

Adult↗
PubMed1995

[Percutaneous extracorporeal circulation in cardiogenic shock caused by combined poisoning with methyldigoxin, nifedipine and indapamide].

HISTORY AND FINDINGS: A 38-year-old man with endogenous depression was found comatose and with gasping respiration. Empty packets of tablets pointed to poisoning with methyldigoxin, nifedipine and indapamide. Pupils reacted slowly to light and no peripheral blood pressure could be measured. TREATMENT AND COURSE: Routine resuscitation measures (intubation, mechanical ventilation, external cardiac massage and drugs) were undertaken during transport to hospital where, in addition to further symptomatic treatment, digoxin antibodies were administered, but without noticeable effect. Percutaneous cardiopulmonary bypass was therefore undertaken. It achieved a cardiac output of 3.2l and a systolic pressure of 80 mm Hg: a stable rhythm and circulation were obtained within 15 hours indicating that electromechanical uncoupling had for the time being been overcome. The EEG suggested a midbrain syndrome. After another 18 hours of mechanical ventilation and symptomatic treatment asystole suddenly occurred. Renewed resuscitation procedures were not undertaken because of the very poor neurological state and prognosis. CONCLUSION: Although haemodynamic stabilization was only temporarily achieved and the patient's death could not be prevented because of adverse pretreatment conditions, the application of percutaneously implantable, transportable heart-lung machine appears to be justified in cases of intoxication with cardio- and vasodepressive substances.

Adult↗
PubMed1995

Recombinant hirudin and front-loaded alteplase in acute myocardial infarction: final results of a pilot study. HIT-I (hirudin for the improvement of thrombolysis).

Recombinant hirudin, a specific thrombin inhibitor, has been shown to accelerate thrombolysis and reduce reocclusions in experimental models. In a pilot trial recombinant hirudin (HBW 023) was used as an adjunctive therapy to thrombolysis with front-loaded tissue plasminogen activator (t-PA) (100 mg.90 min-1) in 40 patients with acute myocardial infarction whose duration of symptoms was less than 6 h. Patients received a bolus of r-hirudin of 0.07 mg.kg-1 b.w. followed by an infusion of 0.05 mg.kg-1.h-1 over 48 h. Complete patency (TIMI grade 3) of the infarct-related artery at 30, 60 and 90 min after the start of thrombolytic therapy was seen in 38.5%, 64.1% and 71.0% of patients, respectively. After 24-48 h, 80% of patients had a complete patent infarct vessel. A very early, complete and sustained patency (TIMI grade 3 at 60 and 90 min and at 24-48 h) was observed in 55% of patients. Reocclusions during the hirudin therapy appeared in six (16.1%) patients, two of whom had a PTCA at 90 min. The only reinfarction was seen after 6 h; this was successfully treated with additional thrombolysis. Major bleedings, mostly related to the invasive procedure, were observed in three patients. Spontaneous organ bleedings and intracerebral haemorrhages did not occur. There was one in-hospital death due to a late retroperitoneal bleeding. In was concluded that, with regard to safety and efficacy, the general feasibility of r-hirudin as adjunctive therapy to thrombolysis with front-loaded t-PA, has been demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Prevention and management of thrombotic complications during coronary interventions. Combination therapy with antithrombins, antiplatelets, and/or thrombolytics: risks and benefits.

Acute occlusions after percutaneous transluminal coronary intervention occur in about 5% of cases. The incidence of these serious adverse events may be reduced by the identification of risk factors, appropriate indication for the intervention, and by medical therapy with antiplatelets and antithrombins. The medical management of complications during percutaneous transluminal interventions also may include thrombolytics. Aspirin has been shown to significantly reduce the incidence of procedure-related coronary occlusion and ischaemic events. Available data suggest pre-treatment with 250-500 mg followed by 100-300 mg aspirin after the intervention. Ticlopidine seems to be equally effective; however, because of its side effects it should be used only in cases of a contra-indication to aspirin. The second indispensable therapeutic concept in the prevention of acute thrombotic events during PTCA is thrombin inhibition. The level of anticoagulation achieved by heparin seems to be critically important. Therefore the recommendation for heparin dosing is a bolus of 10,000 U followed by an intravenous infusion over 24 h of either 1000 U.h-1 or an infusion adjusted to keep the aPTT above 3 times control, but lower doses of shorter duration may be equally effective in uncomplicated cases. Prolonged pre-treatment with heparin may be useful if the pre-intervention angiogram is suggestive of intracoronary thrombus. Thrombolysis as an adjunct to PTCA did not reduce the rate of periprocedural coronary occlusions, but pre-treatment with thrombolysis may be useful in patients with recanalization of occluded vein grafts or in patients with large amounts of thrombotic material. In acute coronary occlusion, thrombolysis has rarely been used as a sole rescue therapy and results have not been encouraging, although a thrombotic process often is involved. Thrombolysis as an adjunct to rescue angioplasty showed no better clinical outcome than prolonged balloon inflation or stenting. Because of serious bleeding complications, thrombolysis should only be considered as a treatment option if thrombosis is unequivocally the major cause of the acute occlusion.

Angioplasty, Balloon, Coronary↗
PubMed1994

Frequency of achieving optimal reperfusion with thrombolysis in acute myocardial infarction (analysis of four German multicenter studies).

Patients from 4 German multicenter studies on thrombolysis in acute myocardial infarction (AMI) were retrospectively evaluated to assess the incidence of optimal reperfusion, defined as a completely perfused infarct vessel after 90 minutes, without subsequent death or reinfarction, and without reocclusion or deterioration of flow in control angiograms. Of 907 patients with a 90-minute angiogram, 75% had an open infarct vessel by conventional definition (perfusion grade 2 or 3 according to the criteria of the Thrombolysis in Myocardial Infarction [TIMI] study). However, only 62% had TIMI grade 3 complete perfusion. Of the 561 patients with such primary treatment success, 106 (19%) had secondary treatment failure by death, reinfarction, or subtotal or total reocclusion of the infarct vessel. In a subset of 668 patients with a first angiogram after 60 minutes, conventional patency was 70%, complete perfusion 51%, and an optimal perfusion result was achieved in only 42%. The efficacy of thrombolysis in AMI is substantially overestimated by conventional 90-minute patency rates.

Adult↗
PubMed1994

Extent of early ST segment elevation resolution: a simple but strong predictor of outcome in patients with acute myocardial infarction.

OBJECTIVES: This study proposed to verify the prognostic power of early ST segment elevation resolution in patients with acute myocardial infarction from the Intravenous Streptokinase in Acute Myocardial Infarction study data base. BACKGROUND: Data from a small prospective study suggested that use of two cutoff points for three different levels of ST segment resolution 3 h after the start of thrombolysis may be an efficient way to predict outcome in an individual patient. METHODS: The three groups of ST segment resolution were defined as 1) complete resolution (> or = 70% [552 patients]) or only slight ST segment elevation (127 patients); 2) partial resolution (< 70% to 30% [475 patients]); 3) no resolution (< 30% to > 0% [362 patients]). Infarct size was measured from creatine kinase isoenzyme, MB fraction, release and from the number of Q waves. Left ventricular function was assessed in 818 patients 1 month after infarction. RESULTS: For complete, partial and no ST segment resolution 3 h after the start of streptokinase or placebo infusion, enzyme release was 1.2, 1.8 and 2.1 IU/ml x h; number of Q waves 1.7, 2.5 and 3.0; and ejection fraction 60%, 53% and 49%, respectively (all adjusted p = 0.0000). Mortality rate at 21 days was 2.2%, 3.4% and 8.6%, respectively. No ST segment resolution was the most powerful independent predictor of early mortality (p = 0.0001). Survival rate curves at 6-year follow-up showed significant mortality differences with increasing divergence (p = 0.0003 anterior infarction; p = 0.005 inferior infarction). In subgroups with an overall higher risk of dying, mortality was strongly determined by the extent of early ST segment resolution. CONCLUSIONS: The extent of ST segment elevation resolution conveys useful early information about outcome in an individual patient after acute myocardial infarction.

Aged↗
PubMed1994

Dose finding with a novel recombinant plasminogen activator (BM 06.022) in patients with acute myocardial infarction: results of the German Recombinant Plasminogen Activator Study. A study of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte (ALKK).

OBJECTIVES: The aim of this study was to determine the appropriate dose of a novel recombinant tissue-type plasminogen activator (BM 06.022) for thrombolysis in patients with acute myocardial infarction. BACKGROUND: BM 06.022 is a mutant of tissue-type plasminogen activator expressed in Escherichia coli that can be given as a single bolus because of a prolonged half-life, which might obviate the need for complicated regimens. METHODS: BM 06.022 given as a single bolus was investigated in 142 patients in a multicenter sequential dose-finding study. Efficacy of the drug was assessed from infarct-related artery patency by coronary angiography. RESULTS: With the first dose of 10 MU of BM 06.022, the predefined minimal 90-min patency of 70% was not achieved, as indicated by the sequential probability ratio test after treatment of 42 patients (group A). The second dose of 15 MU of BM 06.022 was given subsequently in the preset maximum of 100 patients (group B). Angiography 30, 60 and 90 min after the bolus injection of BM 06.022 revealed a patent infarct-related artery (Thrombolysis in Myocardial Infarction trial [TIMI] grade 2 or 3) in 65% and 66%, 73% and 74% and 66% and 75% of patients in groups A and B, respectively. Very early reocclusion up to the 90-min angiogram occurred in 17% and 13%, late reocclusion until predischarge angiography occurred in 7% and 5%, and rescue percutaneous transluminal coronary angioplasty after the 90-min angiogram was performed in 6 and 14 patients in groups A and B, respectively. Plasma fibrinogen decreased from 2.79 g/liter (range 0.94 to 4.75) to 1.69 g/liter (range 0.0 to 3.95) in group A and from 2.54 g/liter (range 0.0 to 5.02) to 0.92 g/liter (range 0.0 to 2.68) in group B. Two bleeding complications requiring transfusion or surgical intervention and one nonfatal intracranial hemorrhage were encountered. Eight patients had a reinfarction, and five patients died, all of cardiac causes. CONCLUSIONS: With BM 06.022 given as a single bolus, a high early patency rate of the infarct-related coronary artery can be achieved. The speed of thrombolysis seems to be superior to standard thrombolytic drugs. The compound warrants further evaluation with respect to safety and efficacy by clinical end points.

Adult↗
PubMed1994

Safety observations from the pilot phase of the randomized r-Hirudin for Improvement of Thrombolysis (HIT-III) study. A study of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte (ALKK)

BACKGROUND: Adjunctive therapy for thrombolysis in acute myocardial infarction consists of platelet inhibition with aspirin and thrombin inhibition with heparin. Thrombin inhibition may be improved by the use of hirudin as indicated by experimental and phase II clinical studies. The randomized, double-blind phase III r-Hirudin for Improvement of Thrombolysis study (HIT III) compared a recombinant hirudin (HBW 023) with heparin. The primary end point was the incidence of death or reinfarction. METHODS AND RESULTS: Seven thousand patients with acute myocardial infarction and a duration of symptoms of less than 6 hours were to be randomized to receive intravenous heparin (70 IU/kg body wt bolus and 15 IU.kg-1.h-1) or hirudin (0.4 mg/kg body wt bolus and 0.15 mg.kg-1.h-1) infused over 48 to 72 hours and adjusted to an activated partial thromboplastin time of 2 to 3.5 times baseline values. In a pilot phase, 1000 patients receiving front-loaded alteplase for thrombolysis were to be recruited by 93 German centers. After enrollment of 302 patients, the trial was stopped after an increased rate of intracranial bleeding was observed in the hirudin group (5 of 148, 3.4%) compared with the heparin group (0 of 154). The overall stroke rate was 3.4% in the hirudin group and 1.3% in the heparin group. Other major bleeding occurred in five versus three patients and ventricular rupture occurred in three versus one patient in the hirudin and heparin groups, respectively. There were 19 in-hospital deaths, with 13 of them from the hirudin group. CONCLUSIONS: Although the number of patients was too small for a definite benefit-risk assessment, at the dosage tested, hirudin in combination with front-loaded alteplase and aspirin may be associated with an increased rate of intracranial hemorrhage. Our findings are consistent with the observations of the GUSTO-II and TIMI-9 trials, where higher doses of another recombinant hirudin were used. Therefore, the therapeutic range of hirudin as an adjunct to thrombolysis may be smaller than previously thought, and reappraisal of dose finding should be considered.

Adult↗
PubMed1994

[Development of new thrombolytic substances].

Early treatment with thrombolytic drugs has been shown to reduce mortality in patients with acute myocardial infarction. Thrombolytic therapy with early, complete and sustained patency of the infarct related artery is associated with a low inhospital mortality of 3 to 4% (Figure 1). Even with the most effective thrombolytic regimens this aim at present is achieved in only about 50% of the patients. The optimal thrombolytic drug should be effective (rapid, complete and sustained recanalization of the infarct related artery), safe (low incidence of severe bleedings), easy to administer (e.g. bolus application) and cost effective. Attempts to improve thrombolytic treatment include the search for better fibrinolytic agents and more effective adjunctive therapies. In the field of adjunctive therapy new more specific thrombininhibitors appear promising and are currently under investigation. In dose-finding studies recombinant hirudin reduced reocclusions and reinfarctions after t-PA thrombolysis. There are several approaches for the improvement of plasminogen activation (Table 1). While new improved dose regimens (e.g. "front-loaded" t-PA) and combination therapies are not subject of this article, it will deal with the recombinant production of naturally occurring plasminogen activators and the development of "designer drugs", which were created in the laboratory by altering the natural occurring molecules t-PA and scu-PA. t-PA contains four domains with different functional properties (Figure 3). Of a variety of mutants and variants of t-PA with altered fibrin-affinity half-life or fibrin specificity one recombinant plasminogen activator (r-PA) is under clinical investigation. r-PA, a deletion mutant of t-PA consisting of the kringle-2 and protease domains, in a dose escalation study (GRECO) showed high early patency rates (Table 2), while there was a trend to a higher incidence of very early reocclusions. In a randomised trial (RAPID), comparing three different r-PA regimens with standard t-PA (100 mg/3 h) a double bolus of 10 MU+ 10 MU r-PA was most effective with regard to early patency (Table 3). Chimeric plasminogen activators (Figure 4) consisting of parts of t-PA and the single-chain urokinase-type plasminogen activator (scu-PA) did not significantly improve at the same time fibrin specificity and thrombolytic potency of the natural occurring molecules. Complexes of plasminogen activators and monoclonal antibodies against platelets or fibrin improve the specificity and thrombolytic activity of the plasminogen activators (Figure 5). However, these molecules are potentially antigenic, costly and not in clinical use yet. Recombinant production of naturally occurring plasminogen activators seems at least as promising as the production of the above mentioned socalled designer drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Designer Drugs↗
PubMed1994

[Different therapeutic regimens in thrombolysis of acute myocardial infarct].

An early, complete, and sustained patency of the infarct related artery achieved by thrombolytic therapy reduces mortality in patients with acute myocardial infarction. In the ISIS-3-study there was no difference in mortality between t-PA, APSAC, and streptokinase. In contrast, in the GUSTO-trial, a "front-loaded" regimen of t-PA (100 mg/90 min) lead to a reduced inhospital mortality compared to streptokinase. This was most likely due to the higher early patency-rate of the infarct-related artery after the front-loaded t-PA. The search for new, more effective, thrombolytic regimens lead to a double-bolus injection of t-PA (2 x 50 mg) which revealed high early patency rates (> 80% TIMI-3 after 90 min). R-PA, a new recombinant plasminogen activator with a prolonged half-life, given as double bolus (2 x 10 MU), also produced high patency rates after 90 min without an increased incidence of reocclusions. Acetylsalicylic acid should be given routinely in every thrombolytic therapy. An anticoagulation with heparin seems to improve the efficacy of the more fibrin-specific thrombolytics t-PA, r-PA, and pro-urokinase. In dose-finding studies the specific thrombin inhibitor hirudin has been shown to significantly reduce reocclusions and reinfarctions compared to heparin. An "optimal thrombolysis" most likely can only be achieved by a thrombolytic agent with a very high early patency combined with an effective adjunctive therapy with platelet aggregation- and thrombin-inhibition.

Fibrinolytic Agents↗
PubMed1993

[The use of a percutaneously connected heart-lung machine during resuscitation in cardiogenic shock after acute myocardial infarct].

A 47-year-old man was referred by an emergency physician to the intensive care unit of a hospital under resuscitation conditions while having recurrent attacks of ventricular fibrillation. Coronary angiography, performed while resuscitation measures had to be maintained, revealed severe three-vessel disease with occlusion of the anterior interventricular branch at its origin. Electrical and haemodynamic instability persisted even after thrombolysis with urokinase and introduction of an intraaortic balloon pump. Percutaneous partial cardiopulmonary bypass (CPB) was, therefore, instituted and a cardiac output of 2.5 1 achieved together with a stable sinus rhythm and a systolic pressure of 60-80 mm Hg. After 9 h on CPB, drug administration could be levelled off and he was mobilised. He showed no neurological deficits and 4 months later he underwent an elective coronary bypass operation. This report demonstrates that even in conditions of resuscitation mechanical circulatory support can be undertaken rapidly and successfully, in the face of electrical instability, to achieve at least temporarily a stable circulation.

Combined Modality Therapy↗
PubMed1993

Open, noncontrolled dose-finding study with a novel recombinant plasminogen activator (BM 06.022) given as a double bolus in patients with acute myocardial infarction.

The novel recombinant plasminogen activator (r-PA) (BM 06.022) is a mutant of tissue-type plasminogen activator expressed in escherichia coli which can be given as a bolus because of a prolonged half-life. The primary objective of this trial was to determine the efficacy of an intravenous r-PA double bolus (first bolus of 10 MU followed by 5 MU after 30 minutes) in patients with acute myocardial infarction. All patients received heparin intravenously and acetylsalicylic acid orally. Efficacy was assessed from infarct artery patency by coronary angiography (Thrombolysis in Myocardial Infarction trial perfusion grades 2 or 3) in 50 patients. Ninety minutes after administration of the first r-PA bolus, the infarct-related coronary artery was patent in 39 of 50 patients (78%; 95% confidence interval 64 to 88%). An angiographically confirmed reocclusion occurred in 1 patient between 90 minutes and 24 to 48 hours. The reocclusion rate was influenced by 8 interventions and 1 angiogram missing at 24 to 48 hours. Measurements of hemostatic parameters showed a decrease in fibrinogen to 37% of baseline value. There were 3 clinical reinfarctions before discharge and 2 major puncture site hemorrhages. No further serious bleeding and no serious adverse event with lethal outcome occurred. The 10 + 5 MU r-PA double bolus regimen appears to be effective with regard to patency and the success of thrombolysis. The incidence of reocclusion is very low. From the limited number of patients treated in this study, one need not be concerned about the safety profile of r-PA.

Clinical Enzyme Tests↗
PubMed1993

Impact of early perfusion status of the infarct-related artery on short-term mortality after thrombolysis for acute myocardial infarction: retrospective analysis of four German multicenter studies.

OBJECTIVE: This study evaluated the impact of early patency of the infarct-related vessel on short-term mortality after thrombolysis for acute myocardial infarction. BACKGROUND: Different thrombolytic regimens for acute myocardial infarction proved to be equally effective in large scale mortality trials despite significant differences in their efficacy with respect to early infarct-related vessel patency as shown in smaller angiographic trials. METHODS: Patients from four German multicenter studies of thrombolysis in acute myocardial infarction were retrospectively evaluated. Of 939 patients with acute myocardial infarction (duration of symptoms < 6 h) treated with thrombolysis, 907 (96.6%) had an angiogram of the infarct-related artery 90 min after the initiation of thrombolytic therapy. The perfusion status was graded according to the Thrombolysis in Myocardial Infarction (TIMI) study criteria. RESULTS: Complete reperfusion (TIMI grade 3) was found in 561 of 907 patients and partial reperfusion (TIMI grade 2) in 122 of 907. Overall, the in-hospital mortality rate was 4.6% (43 patients). In patients with complete reperfusion of the infarct-related vessel, the mortality rate was only 2.7% versus 7.1% in patients with an occluded vessel at the 90-min angiogram. This difference was highly significant in univariate as well as in multivariate analysis. In patients with partial perfusion of the infarct vessel, the mortality rate was 6.6%. CONCLUSIONS: The early perfusion status of the infarct-related artery is an independent predictor of short-term survival. However, only complete early reperfusion is associated with a reduced in-hospital mortality rate whereas patients with partial perfusion (TIMI grade 2) have a short-term prognosis similar to that of patients with persistently occluded infarct vessels. Therefore, when used as a surrogate end point for mortality, only TIMI grade 3 perfusion of the infarct vessel should be interpreted as a treatment success of thrombolysis in acute myocardial infarction.

Adult↗