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Oral glycoprotein IIb/IIa antagonists for unstable angina--is there still a chance for the oral substances?

Abstract
The intravenous glycoprotein IIb/IIIa antagonists abciximab, tirofiban and eptifibatide are well accepted for the therapy of patients with unstable angina and/or as concomitant medication during coronary interventions. Despite the fact that these drugs are not used in all patients presenting with unstable angina during coronary interventions, the scientific evidence is overwhelming including the substantial reduction in mortality 3 years after utilisation of abciximab for coronary interventions in patients with unstable angina. In addition to these two indications, intravenous glycoprotein IIb/IIIa antagonists are currently being investigated for use in patients undergoing carotid artery interventions, peripheral arterial interventions and stroke, as well as adjunct therapy in patients undergoing fibrinolytic therapy during acute myocardial infarction. In contrast, the large trials being performed in patients with unstable angina and following coronary interventions using oral glycoprotein IIb/IIIa antagonists have been very disappointing. There were only minor therapeutic effects detectable, resulting in a slight reduction in ischemic cardiac events in some investigations, however, in all studies, there was a slight trend towards an increased mortality in the glycoprotein IIb/IIIa receptor-antagonist-treated group of patients. In meta-analysis, an approximately 35% relative increase in mortality has been calculated for patients being treated long term with the oral glycoprotein antagonists. The reason for this therapeutic failure is still unknown, however, the limited bioavailability of these drugs, together with our still very limited knowledge about the regulation of the platelet fibrinogen receptor, may be partially responsible for this therapeutic failure. Other compounds with improved pharmacokinetic properties are currently in clinical development.
AuthorsH Darius
JournalThrombosis research (Thromb Res) Vol. 103 Suppl 1 Pg. S117-24 (Sep 30 2001) ISSN: 0049-3848 [Print] United States
PMID11567679 (Publication Type: Journal Article, Review)
Chemical References
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
Topics
  • Administration, Oral
  • Angina, Unstable (complications, drug therapy, mortality)
  • Clinical Trials as Topic
  • Humans
  • Platelet Aggregation Inhibitors (administration & dosage, adverse effects, standards)
  • Platelet Glycoprotein GPIIb-IIIa Complex (antagonists & inhibitors)

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