Association of INR Stability and Bleeding Outcomes Among Atrial Fibrillation Patients Undergoing PCI
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
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.
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Additional Info
Association of International Normalized Ratio Stability and Bleeding Outcomes Among Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention
Circ Cardiovasc Interv 2019 Feb 01;12(2)e007124, M Kerneis, MK Yee, R Mehran, T Nafee, C Bode, JL Halperin, ED Peterson, FWA Verheugt, P Wildgoose, M van Eickels, GYH Lip, M Cohen, KAA Fox, CM GibsonFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Unknowns and Complexity, but Straightforward Nonetheless
This is an important secondary analysis of the PIONEER AF-PCI trial. It is complex and difficult to follow and fully comprehend in that there are multiple groups being analyzed either as part of main trial primary endpoints or in additional exploratory analyses.
The main three primary trial endpoints are:
Group 1 – rivaroxaban 15 mg qd plus a P22 Y12 inhibitor for 12 months; Group 2 – rivaroxaban 2.5 mg bid plus DAPT for 1, 6, or 12 months; Group 3 – dose-adjusted VKA plus DAPT for 1, 6, or 12 months.
Group 3 then has multiple subgroups, including exploratory analyses, which include the percentage of time for the individual patient with an INR within time in therapeutic range (TTR) defined as an INR between 2.0 and 3.0. After that, there are further analyses of three exploratory higher TTR cutoffs—70%, 80%, and 90% time spent in each of these higher TTR ranges, and then sensitivity analysis of different INR ranges, which overlap. The latter analysis is of particular concern in that there is a low INR target TTR of 1.5–2.5 and a narrow INR target between 2.0 and 2.5 with overlap in part of the low INR target range.
Interpretation of this study is difficult or complex; as the authors state, “the impact of TTR for Groups 1 and 2 according to the mean center or country TTR,” which is difficult to understand in that Group 1 and Group 2 patients were not on VKA. In addition, time spent in TTR was not associated with the occurrence of bleeding, which, as the authors suggest, may mean that it is the addition of DAPT to VKA rather than the VKA itself, which may exacerbate the bleeding.
Irrespective of the unknowns and complexity, the results, I believe, are straightforward as the authors conclude: