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


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.
Alexander
J H
JH
Duke University Center and Duke Clinical Research Institute, Durham, NC 27715, USA. alexa017@mc.duke.edu
Yang
H
H
Becker
R C
RC
Kodama
K
K
Goodman
S
S
Dyke
C K
CK
Kleiman
N S
NS
Hochman
J S
JS
Berger
P B
PB
Cohen
E A
EA
Lincoff
A M
AM
Burton
J R
JR
Bovill
E G
EG
Kawai
C
C
Armstrong
P W
PW
Harrington
R A
RA
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D065427:Factor Xa Inhibitors; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000008:administration & dosage / Q000633:toxicity; D006801:Humans; D007511:Ischemia / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D009281:Naphthalenes / Q000008:administration & dosage / Q000633:toxicity; D010314:Partial Thromboplastin Time; D011422:Propionates / Q000008:administration & dosage / Q000633:toxicity; D012697:Serine Endopeptidases / Q000008:administration & dosage* / Q000627:therapeutic use
C086910:(2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid; D065427:Factor Xa Inhibitors; D009281:Naphthalenes; D011422:Propionates; D006493:Heparin; D012697:Serine Endopeptidases