First experience with direct, selective factor Xa inhibition in patients with non-ST-elevation acute coronary syndromes: Results of the XaNADU-ACS Trial

J. H. Alexander, H. Yang, R. C. Becker, K. Kodama, S. Goodman, C. K. Dyke, N. S. Kleiman, J. S. Hochan, P. B. Berger, E. A. Cohen, A. M. Lincoff, J. R. Burton, E. G. Bovill, C. Kawai, P. W. Armstrong, R. A. Harrington

Research output: Contribution to journalReview article

52 Scopus citations

Abstract

Background: Unfractionated heparin is widely used in patients with non-ST-elevation acute coronary syndromes but has important limitations. Anticoagulants with predictable kinetics and anticoagulant effects, better efficacy, and greater safety are needed. Objective: To investigate the efficacy and safety of a direct, selective factor Xa inhibitor, DX-9065a (Daiichi Pharmaceuticals LTD, Inc.) compared with heparin, in patients with non-ST-elevation acute coronary syndromes. Patients and methods: Patients (n = 402) from the USA, Canada, and Japan were randomized to blinded, weight-adjusted heparin, low-dose DX-9065a, or high-dose DX-9065a. Results The primary efficacy end-point of death, myocardial infarction, urgent revascularization, or ischemia on continuous ST-segment monitoring occurred in 33.6%, 34.3%, and 31.3% of patients assigned to heparin, low-dose DX-9065a, and high-dose DX-9065a (P = 0.91 for heparin vs. combined DX-9065a). The composite of death, myocardial infarction, or urgent revascularization occurred in 19.5%, 19.3%, and 11.9% (P = 0.125 for heparin vs. high-dose DX-9065a) of patients; major or minor bleeding occurred in 7.7%, 4.2%, and 7.0% of patients; and major bleeding in 3.3%, 0.8%, and 0.9% of patients. Higher concentrations of DX-9065a were associated with a lower likelihood of ischenonscientificmie events (P = 0.03) and a non-significant tendency toward a higher likelihood of major bleeding (P = 0.32). Conclusions: In this small phase II trial, there was a non-significant tendency toward a reduction in ischemie events and bleeding with DX-9065a compared with heparin in patients with acute coronary syndromes. The absence of an effect on ST-monitor ischemia warrants further investigation. These data provide the rationale for adequately powered studies of DX-9065a in acute coronary syndromes or percutaneous intervention.

Original languageEnglish (US)
Pages (from-to)439-447
Number of pages9
JournalJournal of Thrombosis and Haemostasis
Volume3
Issue number3
DOIs
StatePublished - Mar 2005

Keywords

  • Acute coronary syndromes
  • Anticoagulant
  • Clinical trial
  • Factor Xa inhibitor

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'First experience with direct, selective factor Xa inhibition in patients with non-ST-elevation acute coronary syndromes: Results of the XaNADU-ACS Trial'. Together they form a unique fingerprint.

Cite this