Yuriko Fischer

Changes of hemostasis, endogenous fibrinolysis, platelet activation and endothelins after percutaneous transluminal coronary angioplasty in patients with stable angina.

OBJECTIVES This study investigated parameters of endogenous fibrinolysis, activation of coagulation and platelets, and endothelin levels before and after elective percutaneous transluminal coronary angioplasty (PTCA) in patients with stable coronary artery disease (CAD). BACKGROUND Abrupt vessel closure is a serious short-term complication after PTCA and is often unforeseeable. Detailed insight into the effect of PTCA on hemostasis, platelets and the release of vasoconstrictive substances, which are among the mainly discussed mechanisms of abrupt vessel closure, is needed to enhance the safety of coronary intervention. METHODS Plasma levels of markers of platelet activity, coagulation, endogenous fibrinolysis and endothelins were determined in 20 patients with stable CAD undergoing elective PTCA. The blood specimens were drawn before, immediately after, 1 h after intervention and on the next morning. RESULTS All patients showed an initially uncomplicated PTCA. Regarding the efficacy of anticoagulation after receiving 15.000 IU heparin during PTCA, two groups were compared. In eight patients with ineffective anticoagulation production of thrombin and platelet activation directly after and 1 h after PTCA was significantly higher compared with 12 patients with effective anticoagulation. Despite the strong activation of coagulation, only a low fibrinolytic response could be observed. Endothelins rose significantly after PTCA in both groups but stayed longer on higher levels in patients with distinct thrombin generation. Three of the eight patients without sufficient heparin treatment suffered abrupt vessel closure. CONCLUSIONS Initially uncomplicated dilation of coronary arteries leads to systemically measurable activation of coagulation and platelets in patients with ineffective doses of heparin and release of endothelins in all patients. Therefore, individual adjustment of anticoagulation and platelet inhibition in combination with effective antivasospastic substances are needed in every patient before, during and after initially uncomplicated PTCA to prevent this serious complication.

Antithrombotic treatment in stable coronary syndromes: long-term intermittent urokinase therapy in end-stage coronary artery disease and refractory angina pectoris.

Interventions that modify lipid metabolism and blood coagulation have been shown to favourably influence the natural course of coronary artery disease in terms of the primary prevention and treatment of acute cardiovascular events. Various findings suggest that such interventions may also preserve and enhance myocardial perfusion in the chronic stage of the disease. Long-term intermittent urokinase therapy was developed for patients with end-stage coronary artery disease and refractory angina pectoris. A dose of 500,000 IU of urokinase given intravenously as a bolus three times a week for of 12 weeks reduced symptoms by 70% and was accompanied by objective improvements in myocardial perfusion and an increase of ergometric exercise capacity. The possible therapeutic mechanisms of long-term intermittent urokinase therapy-improvement of rheological blood properties mediated by fibrinogen reduction, thrombolysis of non-occlusive subclinical thrombi, and regression of atherosclerotic plaques-are discussed in the context of other antithrombotic approaches.

Antithrombotische Therapie bei chronischen Koronarsyndromen – Stellenwert der Thrombozytenaggregationshemmung, Antikoagulation und chronischen Thrombolyse

Die antithrombotische Therapie besitzt in der Behandlung von akuten und chronischen Koronarsyndromen einen elementaren Stellenwert. Die Rationale dafür stellt eine verstärkte Thrombozytenaktivierung mit Aktivierung des plasmatischen Gerinnungssystems und damit prokoagulatorischen Mechanismen bei koronarer Herzkrankheit dar. In dieser Arbeit wird der derzeitige Stellenwert der Thrombozytenaggregationshemmung, Antikoagulation und chronischen Thrombolyse in der Therapie von chronischen Koronarsyndromen diskutiert. Derzeit stellt eine niedrig-dosierte Aspirintherapie die Therapie der Wahl bei chronisch stabiler, koronarer Herzkrankheit dar. Darüberhinaus müssen für bestimmte Risikogruppen von Koronarpatienten modifizierte Therapieempfehlungen gegeben werden. So wird eine orale Antikoagulantientherapie bei Patienten empfohlen, welche ein höheres Risiko von muralen Thromben aufweisen. Für die “chronisch-intermittierende Urokinasetherapie” sind exzellente Effekte auf die Verbesserung der klinischen Symptomatik bei therapierefraktären Formen der terminalen koronaren Herzkrankheit beschrieben. Künftige Fortschritte sind von der Einführung oraler Glykoprotein IIb-IIIa-Rezeptorantagonisten und der klinischen Überprüfung antiischämischer Effekte von niedermolekularen Heparinen zu erwarten. Antithrombotic therapy is a basic part in the treatment of acute as well as chronic coronary syndromes. The rationale is an enhanced platelet activity with predomination of procoagulatory mechanisms in coronary artery disease. The current status of antiplatelet drugs, anticoagulation, and chronic thrombolysis used in the treatment of chronic coronary syndromes is discussed. It is concluded that low-dose aspirin is the current drug of choice for long term oral treatment in patients with stable chronic coronary artery disease. In contrast, oral anticoagulation with coumadin should be considered in patients with higher risk for atrial or ventricular thrombosis. The impact of long-term intermittent urokinase therapy in patients with end-stage coronary artery disease and refractory angina pectoris leads to a marked improvement of clinical symptoms. Oral blockade of platelet membrane glycoprotein IIb/IIIa receptor and clinical trials regarding antiischemic effects of low-molecular weight heparins in chronic coronary syndromes are expected for the future.

Medikamentöse Therapie der chronischen Myokardischämie bei koronarer Herzkrankheit

ZusammenfassungIn Hinblick auf die medikamentöse Therapie der chronischen Myokardischämie lassen sich kurz- und langfristige Ziele definieren. Zu den kurzfristigen zählen die Verbesserung der koronaren Vasomotion epikardialer Leitungs- und koronarer Widerstandsgefäße, die Reduktion der Thrombozytenaktivierung sowie die Verbesserung der Fibrinolyse und der Rheologie. Langfristige Ziele sind die Plaque-Stabilisierung und die Reduktion kardiovaskulärer Ereignisse.Für den betroffenen Patienten mit koronarer Herzkrankheit äußert sich der Therapieerfolg in einer Besserung der pectanginösen Beschwerden und somit der Lebensqualität.Um diese subjektive Einschätzung korrekter bewerten zu können, bedient man sich gern der Kriterien der CCS (Canadian Cardiovascular Society)-Klassifikation mit 4 Schweregraden der Angina pectoris.Die vorliegende Arbeit gibt einen gedrängten Überblick über die derzeitigen therapeutischen Strategien der chronischen Myokardischämie. Nicht zuletzt wegen der ungeheuren Bedeutung hinsichtlich Morbidität und Mortalität sowie den gravierenden ökonomischen Folgen der koronaren Herzkrankheit kommt der mdedikamentösen Therapie besonderer Stellenwert zu.