Initial experience with factor-Xa inhibition in percutaneous coronary intervention: the XaNADU-PCI Pilot.

Abstract

BACKGROUND:

Direct factor (F)Xa inhibition is an attractive method to limit thrombotic complications during percutaneous coronary intervention (PCI).

OBJECTIVES:

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.

PATIENTS AND 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.

• Authors: J H Alexander, C K Dyke, H Yang, R C Becker, V Hasselblad, L A Zillman, N S Kleiman, J S Hochman, P B Berger, E A Cohen, A M Lincoff, H Saint-Jacques, S Chetcuti, J R Burton, J M Buergler, F P Spence, Y Shimoto, T L Robertson, S Kunitada, E G Bovill, P W Armstrong, R A Harrington, XaNADU-PCI PILOT Investigators
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 2 Issue 2 Pg. 234-41 (Feb 2004) ISSN: 1538-7933 [Print] England
• PMID: 14995984 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• (2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid
• Anticoagulants
• Factor Xa Inhibitors
• Naphthalenes
• Propionates
• Heparin

Topics

• Aged
• Anticoagulants (administration & dosage, blood, pharmacokinetics)
• Blood Coagulation Tests
• Cardiac Surgical Procedures (adverse effects)
• Dose-Response Relationship, Drug
• Drug Monitoring (methods)
• Factor Xa Inhibitors
• Feasibility Studies
• Female
• Heparin (administration & dosage)
• Humans
• International Normalized Ratio
• Intraoperative Care
• Male
• Middle Aged
• Naphthalenes (administration & dosage, blood, pharmacokinetics)
• Pilot Projects
• Postoperative Complications (prevention & control)
• Propionates (administration & dosage, blood, pharmacokinetics)
• Thrombosis (etiology, prevention & control)