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

Journal Article

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 endpoint 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 ischemic 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 ischemic 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.

Full Text

Duke Authors

Cited Authors

  • Alexander, JH; Yang, H; Becker, RC; Kodama, K; Goodman, S; Dyke, CK; Kleiman, NS; Hochman, JS; Berger, PB; Cohen, EA; Lincoff, AM; Burton, JR; Bovill, EG; Kawai, C; Armstrong, PW; Harrington, RA; XaNADU-ACS INVESTIGATORS,

Published Date

  • March 2005

Published In

Volume / Issue

  • 3 / 3

Start / End Page

  • 439 - 447

PubMed ID

  • 15748230

International Standard Serial Number (ISSN)

  • 1538-7933

Digital Object Identifier (DOI)

  • 10.1111/j.1538-7836.2004.01081.x

Language

  • eng

Conference Location

  • England