Initial experience with factor-Xa inhibition in percutaneous coronary intervention: the XaNADU-PCI Pilot.
BACKGROUND
Direct factor (F)Xa inhibition is an attractive method to limit thrombotic complications during percutaneous coronary intervention (PCI).


OBJECTIVE
To investigate drug levels achieved, effect on coagulation markers, and preliminary efficacy and safety of several doses of DX-9065a, an intravenous, small molecule, direct, reversible FXa inhibitor during PCI.


METHODS
Patients undergoing elective, native-vessel PCI (n = 175) were randomized 4 : 1 to open-label DX-9065a or heparin in one of four sequential stages. DX-9065a regimens in stages I-III were designed to achieve concentrations of > 100 ng mL-1, > 75 ng mL-1, and > 150 ng mL-1. Stage IV used the stage III regimen but included patients recently given heparin.


RESULTS
At 15 min median (minimum) DX-9065a plasma levels were 192 (176), 122 (117), 334 (221), and 429 (231) ng mL-1 in stages I-IV, respectively. Median whole-blood international normalized ratios (INRs) were 2.6 (interquartile range 2.5, 2.7), 1.9 (1.8, 2.0), 3.2 (3.0, 4.1), and 3.8 (3.4, 4.6), and anti-FXa levels were 0.36 (0.32, 0.38), 0.33 (0.26, 0.39), 0.45 (0.41, 0.51), and 0.62 (0.52, 0.65) U mL-1, respectively. Stage II enrollment was stopped (n = 7) after one serious thrombotic event. Ischemic and bleeding events were rare and, in this small population, showed no clear relation to DX-9065a dose.


CONCLUSIONS
Elective PCI is feasible using a direct FXa inhibitor for anticoagulation. Predictable plasma drug levels can be rapidly obtained with double-bolus and infusion DX-9065a dosing. Monitoring of DX-9065a may be possible using whole-blood INR. Direct FXa inhibition is a novel and potentially promising approach to anticoagulation during PCI that deserves further study.
Alexander
J H
JH
Duke University Medical Center and Duke Clinical Research Institute, Durham, NC 27715, USA. alexa017@mc.duke.edu
Dyke
C K
CK
Yang
H
H
Becker
R C
RC
Hasselblad
V
V
Zillman
L A
LA
Kleiman
N S
NS
Hochman
J S
JS
Berger
P B
PB
Cohen
E A
EA
Lincoff
A M
AM
Saint-Jacques
H
H
Chetcuti
S
S
Burton
J R
JR
Buergler
J M
JM
Spence
F P
FP
Shimoto
Y
Y
Robertson
T L
TL
Kunitada
S
S
Bovill
E G
EG
Armstrong
P W
PW
Harrington
R A
RA
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001780:Blood Coagulation Tests; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D065427:Factor Xa Inhibitors; D005240:Feasibility Studies; D005260:Female; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D019934:International Normalized Ratio; D007430:Intraoperative Care; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D010865:Pilot Projects; D011183:Postoperative Complications / Q000517:prevention & control; D011422:Propionates / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*
C086910:(2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid; D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009281:Naphthalenes; D011422:Propionates; D006493:Heparin