The safety and efficacy of several low molecular weight heparins (LMWHs) in the treatment of deep... more The safety and efficacy of several low molecular weight heparins (LMWHs) in the treatment of deep vein thrombosis have recently been established. The available LMWHs differ in physicochemical properties, in vitro activity and pharmacodynamics, but it is not yet known what if any effect these differences exert on clinical efficacy. Clinical trials have compared individual LMWHs with unfractionated heparin or different dose regimens of the same LMWH, but no comparisons between individual LMWHs have been performed. Variations in dosing regimens and patient populations among the trials make meaningful comparisons between individual LMWH efficacy and safety profiles problematic. Thus, while it is likely there are clinical safety and efficacy differences between the LMWH treatment regimens, it will not be possible to characterize one agent as superior to another until head-to-head trials are reported.
Portal vein thrombosis is a rare disorder. The prognosis of both the acute and the chronic forms ... more Portal vein thrombosis is a rare disorder. The prognosis of both the acute and the chronic forms is determined by the resulting acute or chronic portal hypertension. The therapeutic approach of choice is controversial. A case of etiologically unclear thrombosis of the portal vein system in a young man is reported, which was treated successfully by means of portal vein thrombectomy combined with intraoperative and postoperative thrombolysis with recombinant tissue plasminogen activator (rTPA). Initial thrombectomy established sufficient venous return. However, rethrombosis of the portal vein occurred 2 days later. In a second operation rethrombectomy was followed by intraoperative regional application of rTPA, which was continued after operation during a period of 48 hours through a catheter inserted in a mesenteric vein. Patency of the portal system was confirmed 1 week after the procedure. The 1-year follow-up reconfirmed this result (through indirect portography and Doppler sonogr...
The acute coronary syndrome (ACS) remains a major cause of mortality and morbidity in the western... more The acute coronary syndrome (ACS) remains a major cause of mortality and morbidity in the western world. The Global Registry of Acute Coronary Events (GRACE) documents inpatients with all types of ACS and a follow-up at three months in Germany and worldwide. The data of the German Cluster Detmold were compared with data from the worldwide GRACE registry (31,070 patients). Data from 849 patients with ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI) and unstable angina (UA) were collected from October 2001 to September 2005 in eight participating hospitals in the GRACE2 Cluster Detmold. Compared with the worldwide GRACE data the patients in the Cluster Detmold had longer pre-hospital admission times (STEMI patients < 1 h: 13.9 % vs. 17.0 %; p < 0.05); more frequent interventions (PCI 60.1 % vs. 48.7%; p < 0.001) and less thrombolysis (17.9 vs. 42.5%; p < 0.001) in STEMI patients; more frequent use of platelet inhibitors (clopidogrel and ticlopidine, 93.4 % vs. 89.4%; p < 0.001) and unfractionated heparin (69.8 % vs. 36.5; p < 0.001), and less frequent use of low molecular weight heparin (31.1 % vs. 51.2%; p < 0.001); more frequent use of RAS blocking agents (80.2 vs. 66.6, p < 0.001) and beta blockers (87.4 vs. 78.8, p < 0.001) and less frequent use of lipid lowering agents (23.5 vs. 72.5%; p < 0.001). Current management of ACS in Germany closely follows the recommendations of the German society of Cardiology. Differences in practice may account for the observed substantially lower event rates in Germany during hospitalization, but there is still room for improvement in the pre-hospital phase und in the degree to which pharmacotherapy is used for secondary prevention.
... Loren F. Hiratzka, George L. Bakris, Joshua A. Beckman, Robert M. Bersin, Vincent F. Carr, Do... more ... Loren F. Hiratzka, George L. Bakris, Joshua A. Beckman, Robert M. Bersin, Vincent F. Carr, Donald E. Casey Jr, Kim A. Eagle, Luke K ... Geoffrey A. Donnan, Stephen M. Davis, Elizabeth F. Jones, Pierre Amarenco. ... T. Pasierski, S. Jasek, B. Firek, A. Przbylski, H. Szwed, Z. Sadowski ...
Not just since the results of ACCORD, ADVANCE and VADT were published, it is clear that lowering ... more Not just since the results of ACCORD, ADVANCE and VADT were published, it is clear that lowering blood glucose alone does not reduce the cardiovascular risk of patients with type 2 diabetes. In fact, many studies also indicate that some treatment strategies may even have adverse effects. To treat type 2 diabetes appropriately, the co-morbidities such as diabetic dyslipidaemia, hypertension or nephropathy must also be taken into account. Thiazolidinediones reduce insulin resistance thus allowing to direct the treatment of type 2 diabetes towards its pathophysiologic origin. Due to their mechanism of action, thiazolidinediones not only lower blood glucose but have also beneficial effects on inflammatory and atherogenic parameters, blood pressure and microalbuminuria. Furthermore pioglitazone improves dyslipidaemia and reduces mortality, myocardial infarction and stroke in high risk patients. Effects of rosiglitazone on the cardiovascular risk are yet unclear. Numerous studies document...
Zusammenfassung Bei ST-Hebungs-Infarkt ist das Ziel, die Zeit bis zur Reperfusion zu verringern. ... more Zusammenfassung Bei ST-Hebungs-Infarkt ist das Ziel, die Zeit bis zur Reperfusion zu verringern. Neben verspäteter Alarmierung des Notarztes gibt es auch häufig Zeitverluste, weil die vom Notarzt gestellte Diagnose im Krankenhaus in Zweifel gezogen wird und daher Befunde neu erhoben werden. Vertrauensbildende Maßnahmen wie gemeinsame Workshops von Kardiologen und Notärzten können zu einer besseren Kooperation beitragen. Ein weiteres Problem ist
Medizinische Klinik (Munich, Germany : 1983), Jan 15, 2007
Recombinant factor VIIa (rFVIIa) is increasingly used outside the labeled indications for treatme... more Recombinant factor VIIa (rFVIIa) is increasingly used outside the labeled indications for treatment of life-threatening bleeding episodes after failure of the respective standard therapy. An interdisciplinary group of experts summarizes the state of knowledge of the use of rFVIIa in gastroenterology and hepatology, thrombocytopenia and -pathia, coagulation factor deficiencies, von Willebrand's disease, periinterventional bleeding without specific bleeding diathesis, drug-induced bleeding, disseminated intravascular coagulation, and neonatology. The most commonly used dose is 90 microg/kg body weight rFVIIa as bolus, if necessary followed by additional injections at intervals of 2-3 h. In factor VII deficiency lower dosages of 15-30 microg/kg body weight of rFVIIa are given every 4-6 h, whereas higher doses of 150-200 microg/kg body weight are used in neonates.
Thrombin is present at sites of vascular injury and elicits many effects which may contribute to ... more Thrombin is present at sites of vascular injury and elicits many effects which may contribute to neointimal growth. Further studies are needed to order to determine steps involved in thrombin-induced effects and to identify potential sites to regulate these effects. The failure of the Helvetica trial to demonstrate an effect of treatment with hirudin on restenosis may relate more to our inability to safely inhibit thrombin than to a lack of a role for thrombin in restenosis. A therapy which enables safe and effective control of thrombin-induced responses following vascular injury may yet prove effective at reducing restenosis following percutaneous coronary revascularization.
Large efforts have been undertaken to develop more effective and safer thrombolytic agents than t... more Large efforts have been undertaken to develop more effective and safer thrombolytic agents than those currently used in clinical practice. In addition, the value of adjunctive agents influencing thrombotic and thrombolytic processes could be shown and newer agents are under active investigation. This review focuses on theoretical and practical aspects of optimizing thrombolytic therapy and mainly on genetically engineered, third generation plasminogen activators. Optimized thrombolytic therapy may make this form of therapy available to patients that are currently considered ineligible and it may lead to earlier, more complete reperfusion of infarct related coronary arteries. The benefits and risks of optimized thrombolytic regimens relative to mechanical reperfusion strategies will have to be constantly reassessed as both forms of treatment develop.
In 10 patients with coronary artery disease coronary angiograms were performed in identical proje... more In 10 patients with coronary artery disease coronary angiograms were performed in identical projections before and 5, 10 and 15 min after sublingual administration of two chewing capsules with 5 mg of isosorbide dinitrate (ISDN) each. Simultaneously, blood samples were taken for gas-chromatographical determination of nitrate plasma levels. The average ISDN plasma levels amounted to 138 +/- 73 ng/ml, 102 +/- 76 ng/ml and 62 +/- 34 ng/ml in the fifth, tenth and fifteenth min, resp. In the fifteenth min significant isosorbide mononitrate plasma levels (greater than 70 ng/ml) were found only in three patients. Mean diameters of angiographically normal coronary segments were measured with the automatic edge detection system CAAS; they increased by an average of 20 +/- 10%, 26 +/- 11%, and 27 +/- 13% (p less than 0.001) in the fifth, tenth and fifteenth min, resp. Due to hysteresis of the coronary dilation in relation to ISDN plasma levels no significant correlation was found between thes...
During recent years it has become increasingly recognized that the plasmin activation system is i... more During recent years it has become increasingly recognized that the plasmin activation system is involved in the development of atherosclerosis and restenosis. Responsible pathophysiologic mechanisms, however, remain elusive. This review focuses primarily on the clinicians, point of view, suggesting that increases in plasminogen activator inhibitor type-1 (PAI-1) plasma levels after balloon angioplasty or permanently elevated lipoprotein (a) (Lp(a)) plasma levels might be helpful in the prediction of restenosis after coronary angioplasty. In contrast, tissue-type plasminogen activator (tPA) plasma levels appear unrelated to restenosis, and data regarding a possible role of urokinase-type plasminogen activator (uPA) in circulation are not available at present. Furthermore, a new hypothesis on the pathophysiological role of local PAI-1 overexpression as a beneficial negative feedback mechanism to limit excess cellular proliferation in atherogenesis and restenosis is presented.
The monoclonal antibody c7E3 (ReoPro) is a highly selective inhibitor of platelet aggregation tha... more The monoclonal antibody c7E3 (ReoPro) is a highly selective inhibitor of platelet aggregation that binds to the fibrinogen receptor (GP IIb/IIIa) on the surface of platelets and leads to a dose-dependent, nearly complete inhibition of platelet aggregation. The clinical value of c7E3 to reduce ischemic events after PTCA in addition to heparin and aspirin has been demonstrated in the EPIC-, EPILOG-, and CAPTURE-trial. In these studies, c7E3 was associated with an increased bleeding risk after the coronary intervention. The DTREO-Trial (German trial with c7E3) was designed as a prospective study to investigate the clinical safety of c7E3 in the daily routine of a cath lab. From April 1995 through September 1996 520 patients were enrolled at 30 German sites. c7E3 was mainly used in patients with acute coronary syndromes (55% unstable angina Braunwald Class I-III and C; 28% in acute myocardial infarction) and in patients with complex coronary lesions (AHA/ACC classification type B and C ...
In quantitative coronary angiographic studies, unintentional changes of coronary vasomotor tone m... more In quantitative coronary angiographic studies, unintentional changes of coronary vasomotor tone may have a significant influence on the coronary artery diameters, thereby increasing the variability in the measurements. To obtain objective data on these measurement variabilities, two protocols were designed to assess the influences of ionic and nonionic radiographic contrast media on the mean diameters of angiographically normal coronary arteries. The vessel sizes were determined with the CAAS using automated edge detection techniques. In 21 patients (study no. I), coronary angiograms were taken in identical angiographic projections before (control), and immediately following several (at average 7) subsequent diagnostic dye injections administered over a period of about 7 min. The ionic contrast agent diatrizoate 76% induced a coronary dilation of 19 +/- 7% (mean +/- s.d., p less than 0.001; n = 10); the nonionic agent iopromide 370 increased the coronary artery diameters by only 6 +...
The safety and efficacy of several low molecular weight heparins (LMWHs) in the treatment of deep... more The safety and efficacy of several low molecular weight heparins (LMWHs) in the treatment of deep vein thrombosis have recently been established. The available LMWHs differ in physicochemical properties, in vitro activity and pharmacodynamics, but it is not yet known what if any effect these differences exert on clinical efficacy. Clinical trials have compared individual LMWHs with unfractionated heparin or different dose regimens of the same LMWH, but no comparisons between individual LMWHs have been performed. Variations in dosing regimens and patient populations among the trials make meaningful comparisons between individual LMWH efficacy and safety profiles problematic. Thus, while it is likely there are clinical safety and efficacy differences between the LMWH treatment regimens, it will not be possible to characterize one agent as superior to another until head-to-head trials are reported.
Portal vein thrombosis is a rare disorder. The prognosis of both the acute and the chronic forms ... more Portal vein thrombosis is a rare disorder. The prognosis of both the acute and the chronic forms is determined by the resulting acute or chronic portal hypertension. The therapeutic approach of choice is controversial. A case of etiologically unclear thrombosis of the portal vein system in a young man is reported, which was treated successfully by means of portal vein thrombectomy combined with intraoperative and postoperative thrombolysis with recombinant tissue plasminogen activator (rTPA). Initial thrombectomy established sufficient venous return. However, rethrombosis of the portal vein occurred 2 days later. In a second operation rethrombectomy was followed by intraoperative regional application of rTPA, which was continued after operation during a period of 48 hours through a catheter inserted in a mesenteric vein. Patency of the portal system was confirmed 1 week after the procedure. The 1-year follow-up reconfirmed this result (through indirect portography and Doppler sonogr...
The acute coronary syndrome (ACS) remains a major cause of mortality and morbidity in the western... more The acute coronary syndrome (ACS) remains a major cause of mortality and morbidity in the western world. The Global Registry of Acute Coronary Events (GRACE) documents inpatients with all types of ACS and a follow-up at three months in Germany and worldwide. The data of the German Cluster Detmold were compared with data from the worldwide GRACE registry (31,070 patients). Data from 849 patients with ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI) and unstable angina (UA) were collected from October 2001 to September 2005 in eight participating hospitals in the GRACE2 Cluster Detmold. Compared with the worldwide GRACE data the patients in the Cluster Detmold had longer pre-hospital admission times (STEMI patients < 1 h: 13.9 % vs. 17.0 %; p < 0.05); more frequent interventions (PCI 60.1 % vs. 48.7%; p < 0.001) and less thrombolysis (17.9 vs. 42.5%; p < 0.001) in STEMI patients; more frequent use of platelet inhibitors (clopidogrel and ticlopidine, 93.4 % vs. 89.4%; p < 0.001) and unfractionated heparin (69.8 % vs. 36.5; p < 0.001), and less frequent use of low molecular weight heparin (31.1 % vs. 51.2%; p < 0.001); more frequent use of RAS blocking agents (80.2 vs. 66.6, p < 0.001) and beta blockers (87.4 vs. 78.8, p < 0.001) and less frequent use of lipid lowering agents (23.5 vs. 72.5%; p < 0.001). Current management of ACS in Germany closely follows the recommendations of the German society of Cardiology. Differences in practice may account for the observed substantially lower event rates in Germany during hospitalization, but there is still room for improvement in the pre-hospital phase und in the degree to which pharmacotherapy is used for secondary prevention.
... Loren F. Hiratzka, George L. Bakris, Joshua A. Beckman, Robert M. Bersin, Vincent F. Carr, Do... more ... Loren F. Hiratzka, George L. Bakris, Joshua A. Beckman, Robert M. Bersin, Vincent F. Carr, Donald E. Casey Jr, Kim A. Eagle, Luke K ... Geoffrey A. Donnan, Stephen M. Davis, Elizabeth F. Jones, Pierre Amarenco. ... T. Pasierski, S. Jasek, B. Firek, A. Przbylski, H. Szwed, Z. Sadowski ...
Not just since the results of ACCORD, ADVANCE and VADT were published, it is clear that lowering ... more Not just since the results of ACCORD, ADVANCE and VADT were published, it is clear that lowering blood glucose alone does not reduce the cardiovascular risk of patients with type 2 diabetes. In fact, many studies also indicate that some treatment strategies may even have adverse effects. To treat type 2 diabetes appropriately, the co-morbidities such as diabetic dyslipidaemia, hypertension or nephropathy must also be taken into account. Thiazolidinediones reduce insulin resistance thus allowing to direct the treatment of type 2 diabetes towards its pathophysiologic origin. Due to their mechanism of action, thiazolidinediones not only lower blood glucose but have also beneficial effects on inflammatory and atherogenic parameters, blood pressure and microalbuminuria. Furthermore pioglitazone improves dyslipidaemia and reduces mortality, myocardial infarction and stroke in high risk patients. Effects of rosiglitazone on the cardiovascular risk are yet unclear. Numerous studies document...
Zusammenfassung Bei ST-Hebungs-Infarkt ist das Ziel, die Zeit bis zur Reperfusion zu verringern. ... more Zusammenfassung Bei ST-Hebungs-Infarkt ist das Ziel, die Zeit bis zur Reperfusion zu verringern. Neben verspäteter Alarmierung des Notarztes gibt es auch häufig Zeitverluste, weil die vom Notarzt gestellte Diagnose im Krankenhaus in Zweifel gezogen wird und daher Befunde neu erhoben werden. Vertrauensbildende Maßnahmen wie gemeinsame Workshops von Kardiologen und Notärzten können zu einer besseren Kooperation beitragen. Ein weiteres Problem ist
Medizinische Klinik (Munich, Germany : 1983), Jan 15, 2007
Recombinant factor VIIa (rFVIIa) is increasingly used outside the labeled indications for treatme... more Recombinant factor VIIa (rFVIIa) is increasingly used outside the labeled indications for treatment of life-threatening bleeding episodes after failure of the respective standard therapy. An interdisciplinary group of experts summarizes the state of knowledge of the use of rFVIIa in gastroenterology and hepatology, thrombocytopenia and -pathia, coagulation factor deficiencies, von Willebrand's disease, periinterventional bleeding without specific bleeding diathesis, drug-induced bleeding, disseminated intravascular coagulation, and neonatology. The most commonly used dose is 90 microg/kg body weight rFVIIa as bolus, if necessary followed by additional injections at intervals of 2-3 h. In factor VII deficiency lower dosages of 15-30 microg/kg body weight of rFVIIa are given every 4-6 h, whereas higher doses of 150-200 microg/kg body weight are used in neonates.
Thrombin is present at sites of vascular injury and elicits many effects which may contribute to ... more Thrombin is present at sites of vascular injury and elicits many effects which may contribute to neointimal growth. Further studies are needed to order to determine steps involved in thrombin-induced effects and to identify potential sites to regulate these effects. The failure of the Helvetica trial to demonstrate an effect of treatment with hirudin on restenosis may relate more to our inability to safely inhibit thrombin than to a lack of a role for thrombin in restenosis. A therapy which enables safe and effective control of thrombin-induced responses following vascular injury may yet prove effective at reducing restenosis following percutaneous coronary revascularization.
Large efforts have been undertaken to develop more effective and safer thrombolytic agents than t... more Large efforts have been undertaken to develop more effective and safer thrombolytic agents than those currently used in clinical practice. In addition, the value of adjunctive agents influencing thrombotic and thrombolytic processes could be shown and newer agents are under active investigation. This review focuses on theoretical and practical aspects of optimizing thrombolytic therapy and mainly on genetically engineered, third generation plasminogen activators. Optimized thrombolytic therapy may make this form of therapy available to patients that are currently considered ineligible and it may lead to earlier, more complete reperfusion of infarct related coronary arteries. The benefits and risks of optimized thrombolytic regimens relative to mechanical reperfusion strategies will have to be constantly reassessed as both forms of treatment develop.
In 10 patients with coronary artery disease coronary angiograms were performed in identical proje... more In 10 patients with coronary artery disease coronary angiograms were performed in identical projections before and 5, 10 and 15 min after sublingual administration of two chewing capsules with 5 mg of isosorbide dinitrate (ISDN) each. Simultaneously, blood samples were taken for gas-chromatographical determination of nitrate plasma levels. The average ISDN plasma levels amounted to 138 +/- 73 ng/ml, 102 +/- 76 ng/ml and 62 +/- 34 ng/ml in the fifth, tenth and fifteenth min, resp. In the fifteenth min significant isosorbide mononitrate plasma levels (greater than 70 ng/ml) were found only in three patients. Mean diameters of angiographically normal coronary segments were measured with the automatic edge detection system CAAS; they increased by an average of 20 +/- 10%, 26 +/- 11%, and 27 +/- 13% (p less than 0.001) in the fifth, tenth and fifteenth min, resp. Due to hysteresis of the coronary dilation in relation to ISDN plasma levels no significant correlation was found between thes...
During recent years it has become increasingly recognized that the plasmin activation system is i... more During recent years it has become increasingly recognized that the plasmin activation system is involved in the development of atherosclerosis and restenosis. Responsible pathophysiologic mechanisms, however, remain elusive. This review focuses primarily on the clinicians, point of view, suggesting that increases in plasminogen activator inhibitor type-1 (PAI-1) plasma levels after balloon angioplasty or permanently elevated lipoprotein (a) (Lp(a)) plasma levels might be helpful in the prediction of restenosis after coronary angioplasty. In contrast, tissue-type plasminogen activator (tPA) plasma levels appear unrelated to restenosis, and data regarding a possible role of urokinase-type plasminogen activator (uPA) in circulation are not available at present. Furthermore, a new hypothesis on the pathophysiological role of local PAI-1 overexpression as a beneficial negative feedback mechanism to limit excess cellular proliferation in atherogenesis and restenosis is presented.
The monoclonal antibody c7E3 (ReoPro) is a highly selective inhibitor of platelet aggregation tha... more The monoclonal antibody c7E3 (ReoPro) is a highly selective inhibitor of platelet aggregation that binds to the fibrinogen receptor (GP IIb/IIIa) on the surface of platelets and leads to a dose-dependent, nearly complete inhibition of platelet aggregation. The clinical value of c7E3 to reduce ischemic events after PTCA in addition to heparin and aspirin has been demonstrated in the EPIC-, EPILOG-, and CAPTURE-trial. In these studies, c7E3 was associated with an increased bleeding risk after the coronary intervention. The DTREO-Trial (German trial with c7E3) was designed as a prospective study to investigate the clinical safety of c7E3 in the daily routine of a cath lab. From April 1995 through September 1996 520 patients were enrolled at 30 German sites. c7E3 was mainly used in patients with acute coronary syndromes (55% unstable angina Braunwald Class I-III and C; 28% in acute myocardial infarction) and in patients with complex coronary lesions (AHA/ACC classification type B and C ...
In quantitative coronary angiographic studies, unintentional changes of coronary vasomotor tone m... more In quantitative coronary angiographic studies, unintentional changes of coronary vasomotor tone may have a significant influence on the coronary artery diameters, thereby increasing the variability in the measurements. To obtain objective data on these measurement variabilities, two protocols were designed to assess the influences of ionic and nonionic radiographic contrast media on the mean diameters of angiographically normal coronary arteries. The vessel sizes were determined with the CAAS using automated edge detection techniques. In 21 patients (study no. I), coronary angiograms were taken in identical angiographic projections before (control), and immediately following several (at average 7) subsequent diagnostic dye injections administered over a period of about 7 min. The ionic contrast agent diatrizoate 76% induced a coronary dilation of 19 +/- 7% (mean +/- s.d., p less than 0.001; n = 10); the nonionic agent iopromide 370 increased the coronary artery diameters by only 6 +...
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