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

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.

• Authors: Mathieu Kerneis, Megan K Yee, Roxana Mehran, Tarek Nafee, Christoph Bode, Jonathan L Halperin, Eric D Peterson, Freek W A Verheugt, Peter Wildgoose, Martin van Eickels, Gregory Y H Lip, Marc Cohen, Keith A A Fox, C Michael Gibson
• Journal: Circulation. Cardiovascular interventions (Circ Cardiovasc Interv) Vol. 12 Issue 2 Pg. e007124 (02 2019) ISSN: 1941-7632 [Electronic] United States
• PMID: 30704287 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Aged
• Anticoagulants (administration & dosage, adverse effects)
• Atrial Fibrillation (blood, diagnosis, drug therapy)
• Blood Coagulation (drug effects)
• Coronary Artery Disease (blood, diagnosis, therapy)
• Factor Xa Inhibitors (administration & dosage, 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, adverse effects)
• Time Factors
• Treatment Outcome
• Vitamin K (antagonists & inhibitors)
• Warfarin (administration & dosage, adverse effects)