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DOI: 10.1055/s-2003-39973
Einfluss von Molsidomin auf rheologische Parameter und die Inzidenz kardiovaskulärer Ereignisse
Effect of molsidomine on rheological parameters and the incidence of cardiovascular eventsPublikationsverlauf
eingereicht: 18.11.2002
akzeptiert: 3.4.2003
Publikationsdatum:
12. Juni 2003 (online)

Hintergrund und Fragestellung: In-vitro-Untersuchungen haben gezeigt, dass Stickstoffmonooxid (NO) das Potenzial hat, rheologische Parameter zu beeinflussen. Wir untersuchten den Effekt einer hochdosierten Therapie mit dem NO-Donor Molsidomin auf Parameter der Blutrheologie und die Wertigkeit rheologischer Parameter hinsichtlich des Auftretens schwerer kardiovaskulärer Ereignisse.
Patienten und Methodik: In dieser randomisierten, placebokontrollierten und doppelblinden Studie erhielten 166 Patienten (60 ± 10 Jahre) mit stabiler Angina pectoris und Koronarangioplastie täglich retardiertes Molsidomin 3 × 8 mg oder Placebo über 6 Monate. Patienten mit neoplastischen/entzündlichen Erkrankungen oder initial erhöhten Werten für das C-reaktive Protein wurden von der Analyse ausgeschlossen. Ein rheologisches Profil (Plasmaviskosität, Vollblutviskosität, Erythrozytenaggregation, Erythrozytenflexibilität, Leukozytenfiltrabilität, Fibrinogen) wurde initial und nach 6 Monaten erhoben. Innerhalb von 12 Monaten wurden unerwünschte kardiovaskuläre Ereignisse (Tod, Myokardinfarkt, Schlaganfall, koronare/periphere Revaskularisation) dokumentiert. Weiterhin wurde nach im Median 38 Monaten die Wertigkeit der rheologischen Parameter hinsichtlich des Auftretens schwerwiegender Ereignisse (Tod, Myokardinfarkt, Schlaganfall) untersucht.
Ergebnisse: Die Daten von 137 Patienten (n = 71 Placebo, n = 66 Molsidomin) wurden analysiert. Die beiden Gruppen unterschieden sich nicht hinsichtlich der Änderung der rheologischen Parameter zwischen beiden Messpunkten. Die Kaplan-Meier-Analyse des ereignisfreien Überlebens war zwischen den beiden Gruppen sehr ähnlich. In einer multivariaten Cox-Regressionsanalyse, unter Berücksichtigung von Diabetes mellitus, Nikotinkonsum und Statintherapie, waren die Parameter Fibrinogen und Plasmaviskosität signifikant mit dem Auftreten schwerwiegender unerwünschter Ereignisse assoziiert.
Folgerung: Eine Therapie mit täglich 3 × 8 mg retardiertem Molsidomin über 6 Monate führte zu keiner Beeinflussung der rheologischen Parameter und der Inzidenz kardiovaskulärer Ereignisse. Erhöhte Werte für Fibrinogen sowie Plasmaviskosität korrelierten mit dem Auftreten schwerer kardiovaskulärer Ereignisse.
Background and objective: In-vitro studies revealed that nitrit oxide (NO) may affect rheological parameters. We studied the effect of highly-dosed NO-donor molsidomine on blood rheology and the impact of rheological parameters on the incidence of severe cardiovascular events.
Patients and methods: In this randomized, placebo-controlled and double-blind trial 166 patients (60 ± 10 years) with stable angina pectoris and coronary intervention received molsidomine 3 × 8 mg t. i. d. (controlled release tablets) or placebo for 6 months. Patients with inflammatory/neoplastic disorders or elevated values of C-reactive protein were excluded from analysis. A rheological profile (plasma viscosity, blood viscosity, aggregation and flexibility of erythrocytes, filtrability of leukocytes, fibrinogen levels) was done initially and after 6 months. Adverse cardiovascular events (death, myocardial infarction, stroke, coronary/peripheral revascularization) were recorded during 12 months. Furthermore, the impact of rheological parameters regarding the occurrence of severe cardiovascular events (death, myocardial infarction, stroke) was evaluated during a follow-up of median 38 months.
Results: The data of 137 patients (n = 71 placebo, n = 66 molsidomine) were analysed. The difference of rheological parameters between the two measurements did not vary between the two groups. Analysis of event-free survival with Kaplan-Meier technique revealed no difference between the two groups. Multivariate Cox regression analysis with adjustment for diabetes mellitus, smoking and therapy with statine showed a significant association of fibrinogen and plasma viscosity with the occurrence of severe cardiovascular events.
Conclusion: Treatment with molsidomine 3 × 8 mg/day for 6 months does not improve blood rheology or reduce cardiovascular events. But elevated levels of fibrinogen and plasma viscosity were associated with the occurrence of severe cardiovascular events.
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Dr. Jochen Wöhrle
Innere Medizin II, Universitätsklinikum Ulm
Robert-Koch-Straße 8
89081 Ulm
Telefon: +49/0731/50024441
Fax: +49/0731/50024442
eMail: jochen.woehrle@medizin.uni-ulm.de