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Therapie mit CSE-Hemmern — mehr als Lipidsenkung?

Treatment with HMG-CoA reductase inhibitors — More than lipid lowering?

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Zusammenfassung

Die epidemiologisch gesicherten Beziehungen zwischen der Höhe der Cholesterinkonzentration im Plasma und dem Auftreten einer koronaren Herzkrankheit haben zu vielfältigen therapeutischen Anstrengungen geführt, um den Ablauf dieses Geschehens zu beeinflussen. Diätetische Maßnahmen und medikamentöse Eingriffe mit Fibraten, Nikotinsäure und Colestyramin zeigten einen Rückgang der koronaren Ereignisse, aber keinen Einfluß auf die Mortalität. Die Möglichkeit, mit den sehr viel stärker wirksamen CSE-Hemmern massive Senkungen des Gesamtcholesterins und LDL-Cholesterins herbeizuführen, hat zu neuen Erkenntnissen geführt. Studien zur primären Prävention (WOSCOPS, AFCAPS/TexCAPS) sowie zur sekundären Prävention (4S, CARE, LIPID) zeigten übereinstimmend Risikoreduktionen für koronare Ereignisse (tödlicher/nichttödlicher Myokardinfarkt, Notwendigkeit für interventionelle Eingriffe und teilweise auch Angina pectoris). Bei Hochrisikopatienten konnte eine Senkung der Gesamtmortalität nachgewiesen werden. Es gelang erstmals, diese Effekte auch bei Frauen, alten Menschen und Diabetikern nachzuweisen.

Lipidsenkungen wirken sich günstig aus nach Herztransplantation und könnten eine Alternative zur PTCA darstellen. Überraschenderweise war durch die Cholesterinsenkung in vielen Studien auch eine Risikoreduktion für den Schlaganfall zu konstatieren.

Das rasche Eintreten der Wirkung auf die klinischen Ereignisse schon innerhalb des ersten Therapiejahres hat dazu geführt, daß neue Mechanismen diskutiert werden, die mit der Therapie verbunden sind. In-vitro-und In-vivo-Ergebnisse sprechen dafür, daß die Verbesserung der klinischen Parameter durch eine Festigung von Plaques erreicht wird. Beein-flussungen sind denkbar bei den Entzündungsprozessen im Plaque, bei den glatten Muskelzellen, im Bereich der Gerinnung und bei der Beeinflussung des Gefäßtonus. Inwieweit diese Vorgänge durch die Cholesterinsenkung oder durch direkte Wirkung der Medikamente verursacht werden, ist Gegenstand der Forschung.

Abstract

An elevated plasma cholesterol concentration is an established risk factor for coronary heart disease. Dietary and drug interventions with fibrate, nicotinic acid and colestyramine have resulted in a decreased rate of major coronary events but failed to decrease mortality. Studies using the more potent lipid lowering statins have shown remarkable results in primary (WOSCOPS, AFCAPS, TexCAPS) and secondary prevention (4S, CARE, LIPID). The use of these drugs reduced the risk for coronary events as well as the need for interventions. Furthermore, improvement of angina has been shown in several studies. In high-risk patients coronary heart disease associated mortality and overall mortality was reduced. Lowering of cholesterol was shown to be effective in women, older people and diabetics. Lipid lowering improves prognosis after heart transplant and could be an alternative to PTCA. Furthermore it was also shown that cholesterol lowering reduces the incidence of stroke.

New mechanisms are discussed to explain the rapid onset of clinical improvement. Among these are: influences on inflammatory processes in the plaque, on vascular smooth muscle activity, on coagulation and on endothelial dysfunction.

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  1. Medizinische Klinik, Heurich-Lanz-Krankenhaus, Feldbergstraße 68-70, D-68163, Manrtheim

    Achim Weizel

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Weizel, A. Therapie mit CSE-Hemmern — mehr als Lipidsenkung?. Herz 24, 42–50 (1999). https://doi.org/10.1007/BF03043817

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