Peri-procedural use of rivaroxaban in elective percutaneous coronary intervention to treat stable coronary artery disease. The X-PLORER trial

Thromb Haemost. 2015 Aug;114(2):258-67. doi: 10.1160/TH15-01-0061. Epub 2015 Apr 30.

Abstract

Patients on rivaroxaban requiring percutaneous coronary intervention (PCI) represent a clinical conundrum. We aimed to investigate whether rivaroxaban, with or without an additional bolus of unfractionated heparin (UFH), effectively inhibits coagulation activation during PCI. Stable patients (n=108) undergoing elective PCI and on stable dual antiplatelet therapy were randomised (2:2:2:1) to a short treatment course of rivaroxaban 10 mg (n=30), rivaroxaban 20 mg (n=32), rivaroxaban 10 mg plus UFH (n=30) or standard peri-procedural UFH (n=16). Blood samples for markers of thrombin generation and coagulation activation were drawn prior to and at 0, 0.5, 2, 6-8 and 48 hours (h) after start of PCI. In patients treated with rivaroxaban (10 or 20 mg) and patients treated with rivaroxaban plus heparin, the levels of prothrombin fragment 1 + 2 at 2 h post-PCI were 0.16 [0.1] nmol/l (median) [interquartile range, IQR] and 0.17 [0.2] nmol/l, respectively. Thrombin-antithrombin complex values at 2 h post-PCI were 3.90 [6.8]µg/l and 3.90 [10.1] µg/l, respectively, remaining below the upper reference limit (URL) after PCI and stenting. This was comparable to the control group of UFH treatment alone. However, median values for thrombin-antithrombin complex passed above the URL with increasing tendency, starting at 2 h post-PCI in the UFH-alone arm but not in rivaroxaban-treated patients. In this exploratory trial, rivaroxaban effectively suppressed coagulation activation after elective PCI and stenting.

Keywords: Anticoagulation; coronary artery disease; rivaroxaban; thrombosis.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anticoagulants / therapeutic use
  • Antithrombin III / analysis
  • Biomarkers / blood
  • Coronary Disease / surgery*
  • Drug Therapy, Combination
  • Elective Surgical Procedures
  • Factor Xa Inhibitors / administration & dosage
  • Factor Xa Inhibitors / therapeutic use*
  • Female
  • Fibrinolytic Agents / therapeutic use
  • Heparin / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / analysis
  • Peptide Hydrolases / analysis
  • Percutaneous Coronary Intervention*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Postoperative Care
  • Postoperative Complications / blood
  • Postoperative Complications / prevention & control*
  • Prothrombin / analysis
  • Risk Factors
  • Rivaroxaban / administration & dosage
  • Rivaroxaban / therapeutic use*
  • Single-Blind Method
  • Stents
  • Thrombin / biosynthesis
  • Thrombosis / blood
  • Thrombosis / prevention & control*

Substances

  • Anticoagulants
  • Biomarkers
  • Factor Xa Inhibitors
  • Fibrinolytic Agents
  • Peptide Fragments
  • Platelet Aggregation Inhibitors
  • antithrombin III-protease complex
  • prothrombin fragment 1.2
  • Antithrombin III
  • Prothrombin
  • Heparin
  • Rivaroxaban
  • Peptide Hydrolases
  • Thrombin

Grant support

Financial support: This study was funded by Bayer.