Effects of combined therapy of clopidogrel and aspirin in preventing thrombus formation on mechanical heart valves in an ex vivo rabbit model

Thromb Res. 2002 Jul 15;107(1-2):39-43. doi: 10.1016/s0049-3848(02)00185-8.

Abstract

Background: The aim of our study was to investigate the efficacy of the combination of clopidogrel and aspirin in the prevention of thrombus formation on artificial heart valves in an experimental rabbit model as compared to anticoagulation with warfarin.

Methods: Studies were performed after oral administration of clopidogrel and aspirin in group I (n=9) for 5 days, after 5+/-2 days treatment with warfarin in group II (n=9) and without medication in group III (n=9). Leaflets from Sulzer Carbomedics bileaflet valves were placed in a flow chamber. The flow chamber was filled with blood in a continuous circulation between the carotid artery and the jugular vein.

Results: In group III, the flow chamber was clotted after a median of 15 min of circulation. Weight analysis before and after 1 h of perfusion showed that the median thrombus weight was 9.1 mg in group I, 14.4 mg in group II and 33.7 mg in group III. Further analysis by electron microscopy showed fewer platelets and erythrocytes on leaflets in group I than on leaflet surfaces in group II.

Conclusion: Clopidogrel and aspirin were more effective than warfarin in preventing thrombus formation on artificial heart valve leaflets in our investigation. This rabbit model with a high dosage of clopidogrel and aspirin, and a short-time exposure of the heart valve leaflets to rabbit blood under laminar flow, should be further evaluated with respect to whether it can give information about antithrombotic regimens in patients after mechanical heart valve replacement.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspirin / administration & dosage
  • Aspirin / pharmacology*
  • Clopidogrel
  • Drug Evaluation, Preclinical
  • Drug Therapy, Combination
  • Heart Valve Prosthesis / adverse effects*
  • In Vitro Techniques
  • Male
  • Microscopy, Electron
  • Rabbits
  • Thrombosis / drug therapy
  • Thrombosis / pathology
  • Thrombosis / prevention & control*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / pharmacology*
  • Warfarin / pharmacology

Substances

  • Warfarin
  • Clopidogrel
  • Ticlopidine
  • Aspirin