Association of International Normalized Ratio Stability and Bleeding Outcomes Among Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention

Circ Cardiovasc Interv. 2019 Feb;12(2):e007124. doi: 10.1161/CIRCINTERVENTIONS.118.007124.

Abstract

Background: Among atrial fibrillation patients undergoing percutaneous coronary intervention enrolled in PIONEER AF-PCI (An Open-Label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention), it is unclear if the observed reduction in bleeding events with rivaroxaban regimens is consistent across a range of the international normalized ratio (INR) among subjects administrated Vitamin K antagonist (VKA)-triple therapy. This analysis compares the occurrence of clinically significant bleeding between rivaroxaban and VKA strategies, according to INR stability of subjects administrated VKA.

Methods and results: A total of 2124 atrial fibrillation patients undergoing percutaneous coronary intervention were randomized to 3 groups: rivaroxaban 15 mg od plus a P2Y12 inhibitor (group 1, n=709); rivaroxaban 2.5 mg bid plus dual antiplatelet therapy (group 2, n=709); and warfarin plus dual antiplatelet therapy (group 3, n=706). Subjects assigned to the VKA group were stratified according to time in therapeutic range and time spent with an INR >3. Kaplan-Meier estimates were calculated for clinically significant bleeding through 1 year and hazard ratios were derived using Cox Proportional Hazards models. Among group 3, 93.4% of the participants had a time in therapeutic range available (mean time in therapeutic range=65.0±24.8%). Both groups 1 and 2 were associated with a reduction in clinically significant bleeding compared with subjects in group 3, regardless of the time in therapeutic range (hazard ratio ranges=0.53-0.71 and 0.57-0.76; respectively, P<0.05 for all). Rivaroxaban strategies were associated with a reduction in clinically significant bleeding compared with VKA regardless of the proportion of time spent with an INR >3 (hazard ratio ranges=0.59-0.67 and 0.42-0.69; P<0.05 for all).

Conclusions: Among atrial fibrillation patients undergoing percutaneous coronary intervention, rivaroxaban-based therapy was superior to warfarin plus dual antiplatelet therapy in lowering bleeding outcomes regardless of the INR stability.

Clinical trial registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01830543.

Keywords: atrial fibrillation; international normalized ratio; percutaneous coronary intervention; rivaroxaban; warfarin.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Atrial Fibrillation / blood
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Blood Coagulation / drug effects*
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / therapy*
  • Factor Xa Inhibitors / administration & dosage*
  • Factor Xa Inhibitors / adverse effects
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • International Normalized Ratio*
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention* / adverse effects
  • Platelet Aggregation Inhibitors / administration & dosage
  • Predictive Value of Tests
  • Risk Factors
  • Rivaroxaban / administration & dosage*
  • Rivaroxaban / adverse effects
  • Time Factors
  • Treatment Outcome
  • Vitamin K / antagonists & inhibitors
  • Warfarin / administration & dosage*
  • Warfarin / adverse effects

Substances

  • Anticoagulants
  • Factor Xa Inhibitors
  • Platelet Aggregation Inhibitors
  • Vitamin K
  • Warfarin
  • Rivaroxaban

Associated data

  • ClinicalTrials.gov/NCT01830543