Karl-Ludwig Neuhaus
Schering-Plough
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Featured researches published by Karl-Ludwig Neuhaus.
Journal of the American College of Cardiology | 1994
R. Schröder; Rüdiger Dissmann; Thomas Brüggemann; Karl Wegscheider; Thomas Linderer; Ulrich Tebbe; Karl-Ludwig Neuhaus
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.
Journal of the American College of Cardiology | 1989
Karl-Ludwig Neuhaus; Werner Feuerer; Susanne Jeep-Tebbe; Walter Niederer; Albrecht Vogt; Ulrich Tebbe
To improve further the patency rate of infarct-related coronary arteries, the following accelerated dosage regimen of recombinant tissue-type plasminogen activator (rt-PA) was administered to 80 patients with acute myocardial infarction of less than or equal to 6 h duration: 15 mg intravenous bolus, 50 mg infusion over 30 min and 35 mg infusion over the following 60 min. After coronary angiography at 90 min coronary angioplasty was performed in 16 patients and additional thrombolysis in 3 patients. Six patients were not included in the final angiographic analysis, mostly because of borderline ST segment elevations, in order to avoid overestimation of the efficacy of this dose regimen. Four of these had a patent infarct artery; no early angiogram was performed on two. Sixty minutes after the start of infusion, 54 (74%) of 73 patients had a patent infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3) as did 67 (91%) of 74 patients at 90 min. At 24 h, 61 (92.4%) of 66 patients showed a patent infarct artery. Recurrent myocardial ischemia was noted in 12 patients, 7 (9.4%) of whom experienced reinfarction during the hospital stay. Minor local bleeding complications were observed in 14 patients (17.5%). There were four in-hospital cardiac deaths; one patient who underwent additional thrombolysis for recurrent ischemia died from bleeding complications. These results show that a rapid infusion of 100 mg of rt-PA over 90 min yields a high early patency rate of the infarct-related artery without an increase in reocclusion rate and adverse reactions.
Journal of the American College of Cardiology | 2001
Uwe Zeymer; Harry Suryapranata; Jean Pierre Monassier; Grzegorz Opolski; John Davies; Gundars Rasmanis; Gerard C.M. Linssen; Ulrich Tebbe; Rolf Schröder; Rolf Tiemann; Thomas Machnig; Karl-Ludwig Neuhaus
OBJECTIVES We conducted an international, prospective, randomized, double-blind, placebo-controlled phase 2 trial in patients undergoing thrombolytic therapy or primary angioplasty for acute ST-elevation myocardial infarction (MI) to investigate the effect of eniporide on infarct size and clinical outcome. BACKGROUND Experimental studies suggest that the activity of the Na(+)/H(+) exchange (NHE) plays an important role in the unfavorable sequels of myocardial ischemia and reperfusion. Eniporide specifically inhibits the NHE-1 isoform and has been shown to limit infarct size in experimental models. METHODS The primary efficacy end point was the infarct size measured by the cumulative release of alpha-hydroxybutyrate dehydrogenase (alpha-HDBH) (area under the curve [AUC] 0 to 72 h). In stage 1, 50, 100, 150 or 200 mg eniporide given as a 10-min infusion before start of reperfusion therapy were compared with placebo in 430 patients, and in stage 2, 100 and 150 mg eniporide were compared with placebo in 959 patients. RESULTS In stage 1, the administration of 100 mg and 150 mg eniporide resulted in smaller infarct sizes (mean alpha-HBDH AUC in U/ml x h, placebo: 44.2, 100 mg eniporide: 40.2, 150 mg eniporide: 33.9), especially in the angioplasty group. In contrast, in stage 2 there was no difference in the enzymatic infarct size between the three groups (placebo: 41.2, 100 mg eniporide: 43.0, 150 mg eniporide: 41.5). Overall there was no effect of eniporide on clinical outcome (death, cardiogenic shock, heart failure, life-threatening arrhythmias). However, there was a significant reduction of the incidence of heart failure in patients reperfused late (>4 h). CONCLUSIONS In this large study administration of the NHE-1 inhibitor eniporide, before reperfusion therapy in patients with acute ST elevation MI, did not limit infarct size or improve clinical outcome.
Journal of the American College of Cardiology | 1993
Albrecht Vogt; Rainer von Essen; Ulrich Tebbe; Werner Feuerer; Karl-Friedrich Appel; Karl-Ludwig Neuhaus
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.
Circulation | 1994
Karl-Ludwig Neuhaus; R von Essen; Ulrich Tebbe; A. Jessel; H Heinrichs; Wolfgang Mäurer; W Döring; D Harmjanz; V Kötter; E Kalhammer
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.
Journal of the American College of Cardiology | 1992
Karl-Ludwig Neuhaus; Rainer von Essen; Ulrich Tebbe; Albrecht Vogt; Michael Roth; Michael Riess; Walter Niederer; Florian Forycki; Alexander Wirtzfeld; Wolfgang Maeurer; Peter Limbourg; W. Merx; Klaus Haerten
Thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and anisoylated plasminogen streptokinase activator (APSAC) in myocardial infarction has been proved to reduce mortality. A new front-loaded infusion regimen of 100 mg of rt-PA with an initial bolus dose of 15 mg followed by an infusion of 50 mg over 30 min and 35 mg over 60 min has been reported to yield higher patency rates than those achieved with standard regimens of thrombolytic treatment. The effects of this front-loaded administration of rt-PA versus those obtained with APSAC on early patency and reocclusion of infarct-related coronary arteries were investigated in a randomized multicenter trial in 421 patients with acute myocardial infarction. Coronary angiography 90 min after the start of treatment revealed a patent infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3) in 84.4% of 199 patients given rt-PA versus 70.3% of 202 patients given APSAC (p = 0.0007). Early reocclusion within 24 to 48 h was documented in 10.3% of 174 patients given rt-PA versus 2.5% of 163 patients given APSAC. Late reocclusion within 21 days was observed in 2.6% of 152 patients given rt-PA versus 6.3% of 159 patients given APSAC. There were 5 in-hospital deaths (2.4%) in the rt-PA group and 17 deaths (8.1%) in the APSAC group (p = 0.0095). The reinfarction rate was 3.8% and 4.8%, respectively. Peak serum creatine kinase and left ventricular ejection fraction at follow-up angiography were essentially identical in both treatment groups. There were more bleeding complications after APSAC (45% vs. 31%, p = 0.0019).(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of the American College of Cardiology | 1988
Karl-Ludwig Neuhaus; Ulrich Tebbe; Martin Gottwik; Michael A. Weber; Werner Feuerer; Walter Niederer; Winfried Haerer; Frank Praetorius; Klaus-Dieter Grosser; Wolfgang Huhmann; Hans-Wilhelm Hoepp; Guenter Alber; Abdohlhamid Sheikhzadeh; Berthold Schneider
The effects of recombinant tissue plasminogen activator (rt-PA) and urokinase on patency and early reocclusion of infarct-related coronary arteries were investigated in a single blind, randomized multicenter trial in 246 patients with acute myocardial infarction of less than 6 h duration. Both 70 mg of single chain rt-PA with an initial bolus of 10 mg and 3 million units of urokinase with an initial bolus of 1.5 million units were given intravenously over 90 min. The first angiographic study at the end of the infusion revealed a patent infarct-related artery (Thrombolysis in Myocardial Infarction trial [TIMI] grade 2 or 3) in 69.4% of 121 patients given rt-PA versus 65.8% of 117 patients given urokinase (p = NS). Among patients treated within 3 h from symptom onset a patent infarct-related artery was found in 63.9% of 72 patients given rt-PA versus 70% of 70 patients given urokinase (p = NS). There were five cardiac deaths in each group and one fatal intracranial hemorrhage in the rt-PA group. The in-hospital reinfarction rate was 8.9% versus 13.2% for patients treated with rt-PA and urokinase, respectively. There was no difference in left ventricular function at baseline and follow-up catheterization studies. Both drugs were well tolerated and there was no significant difference in cardiovascular or bleeding complications between the two groups. It is concluded that rt-PA and urokinase in the dosages used provide similar efficacy and safety in the treatment of acute myocardial infarction. Reocclusion during the first 24 h may be less frequent after urokinase treatment.
Journal of the American College of Cardiology | 1987
Rolf Schröder; Karl-Ludwig Neuhaus; Alain Leizorovicz; Thomas Linderer; Ulrich Tebbe
Long-term mortality and morbidity of 1,741 patients with acute myocardial infarction, treated with intravenous streptokinase (1.5 million IU/h) or placebo, was assessed in a double-blind placebo-controlled trial (ISAM). At the 7 month follow-up, 94 (10.9%) of the 859 patients in the streptokinase group and 98 (11.1%) of the 882 patients in the placebo group had died; at an average follow-up of 21 months, 14.4% of the streptokinase group and 16.1% of the placebo group had died. The differences were not statistically significant. Long-term mortality was slightly higher in patients with anterior myocardial infarction and streptokinase treatment (20.1 versus 18.4%) and lower in patients with inferior myocardial infarction (10.2 versus 14.2%). Patients with previous myocardial infarction had a higher long-term mortality rate with streptokinase (34.9 versus 21.5% with placebo, p = 0.03). At 7 months, there were significantly more cases of reinfarction in the streptokinase group (7.2 versus 4.5%, p = 0.02). It is concluded that despite a significant limitation of infarct size by intravenous streptokinase, long-term mortality is only slightly reduced and reinfarction is significantly more frequent. Both findings suggest the need for complementary therapy such as revascularization procedures after thrombolysis.
Journal of the American College of Cardiology | 2002
Sorin J. Brener; Nadine Juran; Stephen G. Ellis; Thomas Ivanc; Eric J. Topol; Uwe Zeymer; A.A.Jennifer Adgey; Thomas R. Vrobel; Karl-Ludwig Neuhaus; E. Magnus Ohman; John Strony; Michael M. Kitt
OBJECTIVES This study was designed to test the hypothesis that eptifibatide and reduced-dose tissue plasminogen activator (t-PA) will enhance infarct artery patency at 60 min in patients with acute myocardial infarction (AMI). BACKGROUND Combination fibrin and platelet lysis improves epicardial and myocardial reperfusion in AMI. METHODS Patients were enrolled in a dose finding (Phase A, n = 344) followed by a dose confirmation (Phase B, n = 305) protocol. All patients received aspirin and weight-adjusted heparin and underwent angiography at 60 and 90 min. In Phase A, eptifibatide in a single or double bolus (30 min apart) of 180, 180/90 or 180/180 microg/kg followed by an infusion of 1.33 or 2.0 microg/kg per min was sequentially added to 25 or 50 mg of t-PA. In Phase B, patients were randomized to: 1) double-bolus eptifibatide 180/90 (30 min apart) and 1.33 microg/kg per min infusion with 50 mg t-PA (Group I); 2) 180/90 (10 min apart) and 2.0 g/kg per min with 50 mg t-PA (Group II); or 3) full-dose, weight-adjusted t-PA (Group III). RESULTS In Phase A, the best rate of Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 was achieved using 180/90/1.33 microg/kg per min eptifibatide with 50 mg t-PA: 65% and 78% at 60 and 90 min, respectively. In Phase B, the incidence of TIMI flow grade 3 at 60 min was 42%, 56% and 40%, for Groups I through III, respectively (p = 0.04, Group II vs. Group III). The median corrected TIMI frame count was 38, 33 and 50, respectively (p = 0.02). TIMI major bleeding was reported in 8%, 11% and 6%, respectively; intracranial hemorrhage occurred in 1%, 3% and 2% of patients (p > 0.5 for both). The incidences of death (4%, 5% and 7%), reinfarction or revascularization at 30 days were similar among the three treatment groups. CONCLUSIONS In comparison with standard t-PA regimen, double-bolus eptifibatide (10 min apart) with a 48-h infusion and half-dose t-PA (Group II) is associated with improved quality and speed of reperfusion. The safety profile of this therapy is similar to that of other combination regimens.
Circulation | 2003
Uwe Zeymer; Rainer Uebis; Albrecht Vogt; Hans-Georg Glunz; Hans-Friedrich Vöhringer; Dietrich Harmjanz; Karl-Ludwig Neuhaus
Background—Percutaneous transluminal coronary angioplasty of the infarct-related artery in stable survivors of acute myocardial infarction is often performed, even in patients without any symptoms or residual ischemia. Despite the lack of randomized studies, it is widely believed that this intervention will improve the clinical outcome of these patients. Methods and Results—Three hundred patients with single vessel disease of the infarct vessel and no or minor angina pectoris in the subacute phase (1 to 6 weeks) after an acute myocardial infarction were randomized to angioplasty (n=149) or medical therapy (n=151). Primary end point was the survival free of reinfarction, (re)intervention, coronary artery bypass surgery, or readmission for severe angina pectoris at 1 year. The event-free survival at 1 year was 82% in the medical group and 90% in the angioplasty group (P =0.06). This difference was mainly driven by the difference in the need for (re)interventions (20 versus 8, P =0.03). At long-term follow-up (mean, 56 months), survival was 89% and 96% (P =0.02). Survival free of reinfarction, (re)intervention, or coronary artery bypass surgery was 66% and 80% in the medically and interventionally treated patients, respectively (P =0.05). The use of nitrates was significantly lower in the angioplasty group, both at 1 year (38% versus 67%, P =0.001) and at long-term follow-up (36% versus 55%, P =0.006). Conclusions—Percutaneous revascularization of the infarct-related coronary artery in stable patients with single vessel disease improves clinical outcome at long-term follow-up and reduces the use of nitrates. The results of our study should be reproduced in a confirmatory study with a larger sample size before percutaneous coronary intervention in this low-risk patient subgroup, after myocardial infarction can be recommended as routine treatment in clinical practice.