Open AccessImpact of Global Geographic Region on Time in Therapeutic Range on Warfarin Anticoagulant Therapy: Data From the ROCKET AF Clinical Trial
Author(s) -
Singer Daniel E.,
Hellkamp Anne S.,
Piccini Jonathan P.,
Mahaffey Kenneth W.,
Lokhnygina Yuliya,
Pan Guohua,
Halperin Jonathan L.,
Becker Richard C.,
Breithardt Günter,
Hankey Graeme J.,
Hacke Werner,
Nessel Christopher C.,
Patel Manesh R.,
Califf Robert M.,
Fox Keith A. A.
Publication year - 2013
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.112.000067
Subject(s) - medicine , warfarin , interquartile range , atrial fibrillation , vitamin k antagonist , transthyretin , cardiology
Background Vitamin K antagonist ( VKA ) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range ( TTR ) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial. Methods and Results TTR (international normalized ratio [ INR ] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i‐ TTR ) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i‐ TTR was 55.2% (SD 21.3%) and the median i‐ TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR <2 was 29.1% and the mean time with an INR >3 was 15.7%. While multiple clinical features were associated with i‐ TTR , dominant determinants were previous warfarin use (mean i‐ TTR of 61.1% for warfarin‐experienced versus 47.4% in VKA ‐naïve patients) and geographic region where patients were managed (mean i‐ TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i‐ TTR s had INR distributions shifted toward lower INR values and had longer inter‐ INR test intervals. Conclusions Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i‐ TTR in global studies of warfarin. Regional differences in mean i‐ TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing. Clinical Trial Registration URL: ClinicalTrials.gov . Unique identifier: NCT 00403767.