title: [Effect of molsidomine on rheological parameters and the incidence of cardiovascular events].
abstract: OBJECTIVE
  In-vitro studies revealed that nitric 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.
  
  
  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 x 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 statin showed a significant association of fibrinogen and plasma viscosity with the occurrence of severe cardiovascular events.
  
  
  CONCLUSIONS
  Treatment with molsidomine 3 x 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.
authors.affiliation: Abteilung Innere Medizin II, Universität Ulm. jochen.woehrle@medizin.uni-ulm.de
authors.forename: J
authors.initials: J
authors.lastname: Wöhrle
authors.forename: T
authors.initials: T
authors.lastname: Nusser
authors.forename: A
authors.initials: A
authors.lastname: Hoffmeister
authors.forename: H A
authors.initials: HA
authors.lastname: Kestler
authors.forename: O C
authors.initials: OC
authors.lastname: Grebe
authors.forename: M
authors.initials: M
authors.lastname: Höher
authors.forename: V
authors.initials: V
authors.lastname: Hombach
authors.forename: W
authors.initials: W
authors.lastname: Koenig
authors.forename: M
authors.initials: M
authors.lastname: Kochs
mesh_terms: D001809:Blood Viscosity / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004903:Erythrocyte Aggregation / Q000187:drug effects; D004907:Erythrocyte Deformability / Q000187:drug effects; D005260:Female; D005340:Fibrinogen / Q000032:analysis* / Q000187:drug effects; D006801:Humans; D015994:Incidence; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008981:Molsidomine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012212:Rheology / Q000187:drug effects; D016019:Survival Analysis; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; D005340:Fibrinogen; D008981:Molsidomine