Konservative Therapieansätze bei terminaler koronarer Herzkrankheit
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Zusammenfassung
Trotz Fortschritten in der invasiven Revaskularisation und des unbestrittenen Erfolges der konventionellen antianginösen Therapie nimmt die Zahl von Patienten mit schwerer koronarer Herzkrankheit und einer therapierefraktären Beschwerdesymptomatik zu. Für die „therapierefraktären” Patienten wurde als eine antithrombotische Weiterentwicklung die chronisch-intermittierende Urokinasetherapie als ein neuartiges, mikrozirkulatorisch wirksames Therapieprinzip entwickelt, deren Wirkung auf einer Kombination aus rheologischen und fibrinolytischen Mechanismen sowie möglicherwiese auf einer Plaqueregression beruht.
Das Koronarsyndrom der „therapierefraktären” Angina pectoris ist durch eine schwere, nicht revaskularisierbare koronare Herzkrankheit mit einer vergleichsweise nur gering eingeschränkten linksventrikulären Funktion gekennzeichnet. Vor der Indikationsstellung zur chronisch-intermittierenden Urokinasetherapie muß eine konsequente Ausschöpfung der konservativen Therapiemaßnahmen einschließlich zusätzlicher Therapiemaßnahmen wie der LDL-Cholesterinsenkung erfolgen, die nach aktuellen Daten eine antiischämische und somit potentiell antianginöse Wirksamkeit infolge einer Verbesserung der Endothelfunktion der epikardialen Leitungsgefäße aufweist.
Neben einer in systematischen Untersuchungen objektivierbaren antiischämischen Wirksamkeit der chronisch-intermittiierenden Urokinasetherapie zeigen sich bei Patienten mit ischämischer Herzinsuffizienz darüber hinaus vielversprechende hämodynamische Therapieeffekte auf die diastolische und systolische Funktion unter Belastung. So konnten Ergebnisse der Radionuklidventrikulographie eine signifikante Steigerung der linksventrikulären Ejektionsfraktion unter Belastung aufzeigen. Eine Normalisierung diastolischer Funktionsparameter konnte ebeso nach zwölf Wochen chronisch-intermittierender Urokinasetherapie nachgewiesen werden. Diese antiischämischen und hämodynamischen Therapieeffekte führen zu einer eindrucksvollen Besserung der Lebensqualität dieser Patienten, so daß sich dieses aufwendige Therapieprinzip auch vor dem Hintergrund der in der Regel über zwölf Monate anhaltenden Wirkung rechtfertigt.
Schlüsselwörter
LDL-Cholesterinsenkung Endothelfunktion Thrombotische Progression Chronische Thrombolyse Endstadium der KHKLong-Term Urokinase Treatment in End-Stage Coronary Artery Disease
Summary
Despite progress in the invasive revascularization procedures and even though conventional antianginal treatment has improved the quality of life in patients with symptomatic coronary artery disease considerably, an increasing number of patients suffers from end-stage coronary artery disease and refractory angina pectoris. For these refractory patients longterm intermittent urokinase therapy was developed as an antithrombotic intervention, which is based on its capacity to enhance thrombolysis and blood rheology, and may possibly lead to plaque regression.
The coronary syndrome of refractory angina pectoris is characterized by a mismatch of severe coronary insufficiency and a relatively large amount of viable myocardium as indicated by an only moderately impaired left ventricular function. Prior to initiation of long-term intermittent urokinase therapy all potential measures to improve myocardial perfusion have to be considered in each patient. These supportive measures include rigorous reduction of LDL-cholesterol, which has proven antiischemic properties due to an improved endothelial function of epicardial conductance vessels possibly resulting in an antianginal effect.
Apart from the proven antiischemic properties of long-term intermittent urokinase therapy in patients with refractory angina pectoris, objective signs of ischemic myocardial heart failure improve. Follow-up studies demonstrated a significant increase of left ventricular ejection fraction as evaluated with multi-gated blood pool analysis. Furthermore, left ventricular diastolic function normalized after a treatment period of 12 weeks. As the clinical effects last well beyond the actual treatment period and as they are accompanied by a remarkable increase in the quality of life, a complex approach as this one is justified in this highly symptomatic patient group.
Key Words
LDL-cholesterol reduction Endothelial function Thrombotic progression Chronic thrombolysis End-stage CADPreview
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Literatur
- 1.Anderson TJ, Meredith JT, Yeung AC, Frei B, Selwyn AP, Ganz P. The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent vasomotion. N Engl J Med 1995;332: 488–93.PubMedCrossRefGoogle Scholar
- 2.Andrews TC, Raby K, Barry J, Naimi CL, Allred E, Ganz P, Selwyn AP. Effect of the reduction of cholesterol-reduction on myocardial ischemia in patients with coronary disease. Circulation 1997;95:324–8.PubMedGoogle Scholar
- 3.Benson H, Mc Callie DP.: Angina pectoris and the placebo effect. N Engl J Med 1978;300:1424–9.Google Scholar
- 4.Beyer M. Kardiomyopexie — aktueller Stand eines indirekten Revaskularisationsverfahrens. Z Kardiol 1997;86:Suppl 1: 125–32.PubMedGoogle Scholar
- 5.Bini A, Fenoglia JJ, Mesa Tejeda R, Kudryk B, Kaplan KL. Identification and distribution of fibrinogen, fibrin and fibrin(ogen) degradation products in atherosclerosis: use of monoclonal antibody. Atherosclerosis 1989;9:109–21.Google Scholar
- 6.Boven ADJ van, Jukema JW, Zwinderman AH, Crijns HJGM, Lie KL, Bruschke AVG, on behalf of the Regress Study Group. Reduction of transient myocardial ischemia in addition to the conventional treatment in patients with angina pectoris. Circulation 1996;94:1503–5.PubMedGoogle Scholar
- 7.Braunwald E, Jones RH, Mark DB, Brown J, Cheitlin MD, Concannas CA, Cohan M, Edwards C, Fuster V, Goldman L, Green LA, Grihes C, Lytle BW, Mc Cauley KM, Mushlin AI, Rose GC, Smith EE, Swain JA, Topol EJ, Willerson JT. Diagnosing and managing unstable angina. Circulation 1994;90:613–22.PubMedGoogle Scholar
- 8.Broadhurst P, Kellher C, Hughes L. Fibrinogen, factor VII clotting activity and coronary artery disease severity. Atherosclerosis 1990;85:169–73.PubMedCrossRefGoogle Scholar
- 9.Campeau L. Grading of angina pectoris. Circulation 1976; 54:522–3.PubMedGoogle Scholar
- 10.Davies MJ, Thomas AC, Knapman PA, Hangartner JR. Intramyocardial platelet aggregation in patients with unstable angina suffering sudden ischemic cardiac death. Circulation 1986;73:418–27.PubMedGoogle Scholar
- 11.de Jongste ML, Hautvast RWM, Hillege HL, Lie IL. Efficacy of spinal cord stimulation as adjuvant therapy for intractable angina pectoris: A prospective, randomized clinical study. J Am Coll Cardiol 1994;23:1592–7.PubMedGoogle Scholar
- 12.Egashira K, Hirooka Y, Kai H, Sugimachi M, Suzuki S, Inou T, Takeshita A. Reduction in serum cholesterol with pravastatin improves endothelium dependent coronary vasomotion in patients with hypercholesteroleomia. Circulation 1994;89: 2519–24.PubMedGoogle Scholar
- 13.Ehrly AM, Schenk JF. Systemisch niedrig dosierte Langzeit-Urokinasetherapie bei schwerster Angina pectoris. Grundlagen und erste Ergebnisse: In: Strauer BE, Ehrly AM, Leschke M, eds. Fortschritte in der kardiovaskulären Rehologie. München: Münchner Wissenschaftliche Publikationen, 1987:35–8.Google Scholar
- 14.Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 1995;92:657–71.PubMedGoogle Scholar
- 15.Falk E. Unstable angina with fatal outcome: Dynamic coonary thrombosis leading to infarction and/or sudden death: Autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in vascular occlusion. Circulation 1985; 71:699–708.PubMedGoogle Scholar
- 16.Fuster V, Badimon L, Badimon J, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes (first of two parts). N Engl J Med 1992;326:242–50.PubMedGoogle Scholar
- 17.Fuster V, Badimon L, Badimon J, Chesebro J. The pathogenesis of coronary artery disease and the acute coronary syndromes (second of two parts). N Engl J Med 1992;326:310–8.PubMedGoogle Scholar
- 18.Gotto A. Lipid lowering, regression and coronary events. A review of the Interdisciplinary Council on Lipids and Cardiovascular Risk Intervention. 7th council meeting. Circulation 1995; 92:646–56.PubMedGoogle Scholar
- 19.Gould KL, Martucci JP, Goldberg DI, Hess MJ, Edens RP, Latifi R, Dudrick SJ. Short-term cholesterol lowering decreases size and severity of perfusion abnormalities by positron emission tomography after dipyridamole in patients with coronary artery disease. Circulation 1994;89:1530–8.PubMedGoogle Scholar
- 20.Horvath KA, Cohn LH, Cooley DA, Crew JR, Frazier OH, Griffith BP, Kadipasoglu K, Lansing A, Mannting F, March R, Mirhoseini MR, Smith C. Transmyocardial laser revascularization: results of a multi-center trial using TLR as a sole therapy for endstage coronary artery disease. J Thorac Cardiovasc Surg 1997;113:645–53.PubMedCrossRefGoogle Scholar
- 21.Kaiser GC, Davis KB, Fisher LD, Myers WO, Foster ED, Passamani ER, Gillespie MJ. Survival following coronary bypass grafting in patients with severe angina pectoris (CASS). J Thorac Cardiovasc Surg 1985;89:513–24.PubMedGoogle Scholar
- 22.Kaski JC, Chester MR, Chen L, Katritsis D. Rapid angiographic progression of coronary artery disease in patients with angina pectoris — The role of complex lesion morphology. Circulation 1995;92:2058–65.PubMedGoogle Scholar
- 23.Kurz T, Rauch B, Kübler W. Antianginöse Therapie der koronaren Herzerkrankung. Mono- oder Kombinationsbehandlung. Z Kardiol 1991;80:305–16.PubMedGoogle Scholar
- 24.Leschke M, Blanke H, Stellwaag M, Motz W, Strauer BE. Hyperfibrinogenämie und pathologische Plasmaviskosität. Dtsch Med Wochenschr 1988;113:1175–81.PubMedCrossRefGoogle Scholar
- 25.Leschke M, Höffken H, Motz W, Blanke H, Schoebel FC, Strauer BE. Chronisch intermittierende Urokinasetherapie bei therapierefraktäter Angina pectoris. Dtsch Med Wochenschr. 1992; 117:81–7.PubMedCrossRefGoogle Scholar
- 26.Leschke M, Schoebel FC, Strauer BE. Symptomatische therapierefraktäre Myokardischämie bei koronarer Herzkrankheit. Internist (Berlin) 1996;37:597–606.Google Scholar
- 27.Leschke M, Schoebel FC, Mecklenbeck W, Stein D, Jax TW, Müller-Gärtner HW, Strauer BE. Long-term intermittent urokinase therapy in patients with end-stage coronary artery disease and refractory angina pectoris: A randomized dose-response trial. J Am Coll Cardiol 1996;27:575–84.PubMedCrossRefGoogle Scholar
- 28.Leschke M, Schoebel FC, Heins M, Strauer BE. Antithrombotic treatment for the preservation and enhancement of myocardial perfusion in chronic coronary artery disease. Fibrinolysis and Proteolyis 1997;11:Suppl 1:119–23.CrossRefGoogle Scholar
- 29.Leschke M, Schoebel FC, Schannwell CM, Peters AJ, Jax TW, Mecklenbeck W, Strauer BE. Chronisch intermittierende Urokinasetherapie: antiischämische und hämodynamische Effekte. Z Kardiol 1997;86:Suppl 1:85–94.PubMedGoogle Scholar
- 30.Leung WH, Lau CP, Wong CK. Beneficial effect of cholesterol-lowering therapy on coronary endothelium-dependent relaxation in hypercholesterolemic patients. Lancet 1993;341:1496–500.PubMedCrossRefGoogle Scholar
- 31.Maisch B, Funck R, Schönian U, Moosdorf R. Indikation zur transmyokardialen Lasertherapie. Z Kardiol 1996;85:Suppl 6 269–79.PubMedGoogle Scholar
- 32.Mannheimer C, Augustinsson LE, Carlsson CA, Manhem K, Wilhelmsson C. Epiduralspinal electrical stimulation in severe angina pectoris. Br Heart J 1988;59:56–61.PubMedCrossRefGoogle Scholar
- 33.Maseri A, Chierchia S, Kaski JC. Mixed angina pectoris. Am J Cardiol 1985;56:30E-3E.PubMedCrossRefGoogle Scholar
- 34.Moosdorf R, Schoebel FC, Hort W. Transmyokardiale Laserrevaskularisation — morphologische, pathomorphologische und histologische Grundlagen der indirekten Revaskularisation des Herzmuskels. Z Kardiol 1997;86:149–64.PubMedCrossRefGoogle Scholar
- 35.Nägele H, Kalmar P, Labeck M, Marcsek P, Nienhaber CA, Rödiger W, Stiel GM, Stubbe HM. Transmyokardiale Laserrevaskularisation — Behandlungsoption bei der koronaren Herzerkrankung? Z Kardiol 1997;86:171–8.PubMedCrossRefGoogle Scholar
- 36.Nesto RW, Kowalchuk GJ. The ischemic cascade: Temporal sequence of hemodynamic, electrocardiographic and symptomatic expressions of ischemia. Am J Cardiol 1987;57:23C-30C.CrossRefGoogle Scholar
- 37.Parker JD, Parker AB, Farell B, Parker JO. Effects of diuretic therapy on the development of tolerance to nitroglycerin and exercise capacity in patients with chronic stable angina. Circulation 1996;93:691–6.PubMedGoogle Scholar
- 38.Schmid-Schönbein H. Myokardiale Mikrozirkulation. Wechselwirkung zwischen Vasomotorik und Fließeigenschaften des Blutes. Dtsch Med Wochenschr 1981;106:1483.PubMedCrossRefGoogle Scholar
- 39.Schneidau A, Harrison MJG, Hurst C, Wilkers HC, Meade TW. Arterial disease risk factors and angiographic evidence of atheroma of the carotid artery. Stroke 1989;20:1466–71.PubMedGoogle Scholar
- 40.Schoebel FC, Leschke M, Strauer BE. Therapierefraktäre Angina pectoris im Endstadium der koronaren Herzkrankheit — Pathophysiologische Grundlagen und alternative Therapieansätze. Dtsch Med Wochenschr 1995;120:301–307.PubMedCrossRefGoogle Scholar
- 41.Schoebel FC, Leschke M, Heintzen MP, Strauer BE. Konservative Behandlungskonzepte für die stabile Angina pectoris bei koronarer Herzkrankheit. Med Klin 1996;91:458–65.Google Scholar
- 42.Schoebel FC, Gradaus F, Jax TW, Stiegler HM, Stein DA, Borries M, Kelm M, Strauer BE, Leschke M. Die Bedeutung der Koronarthrombose für die chronische Myokardischämie. Z Kardiol 1997;86:Suppl 1:71–83.PubMedGoogle Scholar
- 43.Schoebel FC, Jax TW, Fischer Y, Strauer BE. Antithrombotic treatment in stable coronary syndromes: long-term intermittent urokinase therapy in end-stage coronary artery disease and refractory angina pectoris. Heart 1997;77:13–7.PubMedGoogle Scholar
- 44.Schoebel FC, Frazier OH, Jessurun GAJ, de Jongste MJL, Kadipasaoglu KA, Jax TW, Heintzen MP, Cooley DA, Strauer BE, Leschke M. Refractory angina pectoris in end-stage coronary artery disease — Evolving therapeutic concepts. Am Heart J (in press).Google Scholar
- 45.Schuff-Werner P, Gohlke H, Bartmann U, Baggio G, Corti MC, Dinsenbacher A, Eisenhauer T, Grützmacher P, Keller C, Kettner U, Kleophas W, Köster W, Olbricht CJ, Richter WO, Seidel D & The HELP-Study Group. The HELP-LDL-apharesis multicenter study, an angiographically assessed trial on the role of LDL-apharesis in the secondary prevention of coronary heart disease. II Final evaluation of the effect of regular treatment on LDL-cholesterol plasma concentrations and the course of coronary heart disease. Eur J Clin Invest 1994;24:724–32.PubMedCrossRefGoogle Scholar
- 46.Shub C. Stable angina pectoris: 3. Medical treatment. Mayo Clin Proc 1990;65:256–73.PubMedGoogle Scholar
- 47.Siegrist J, Broer M, Junge A. Profil der Lebensqualität Chronischkranker. Göttingen-Toronto:Hogrefe, 1995.Google Scholar
- 48.Smith EB, Kean A, Grant A, Stirk D. Fate of fibrinogen in human arterial intima. Arteriosclerosis 1990;10:263–75.PubMedGoogle Scholar
- 49.Tolins M, Weir EK, Chesler E, Pierpont GL. “Maximal” drug therapy is not necessarily optimal in chronic angina pectoris. J Amer Coll Cardiol 1984;3:1051–7.CrossRefGoogle Scholar
- 50.Treasure CB, Klein JL, Weintraub WS, Talley J, Stillablower ME, Kosinski AS, Zhang J, Bocuzzi SJ, Cedarholm JC, Alexander W. Beneficial effect of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med 1995;332:481–7.PubMedCrossRefGoogle Scholar
- 51.Yusuf S, Zucker D, Peduzzi P, Fischer LD, Takaro T, Kennedy JD, Davis K, Killip T, Passamani E, Norris E, Morris C, Mathur V, Varanauskas E, Chalmers TC. Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomised trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet 1994;344:563–70.PubMedCrossRefGoogle Scholar