Outcomes associated with warfarin time in therapeutic range among US veterans with nonvalvular atrial fibrillation

Abstract

Background: Poor quality of warfarin control (time in therapeutic range [TTR] < 65%) can lead to increased risk of adverse events. The objective of this study was to examine the overall quality of international normalized ratio (INR) control and the association of TTR with clinical outcomes including stroke, major bleeding, and all-cause mortality among US warfarin users.

Methods and results: This retrospective observational cohort study utilized the US Veterans Affairs electronic medical records database (VA EMR). Patients with NVAF who newly initiated warfarin from 1 January 2005 to 31 December 2015 were grouped into two cohorts based on TTR <65% or ≥65%. TTR was computed from INR test results. Clinical outcomes assessed were stroke/systemic embolism (SE), hemorrhagic stroke, ischemic stroke, and major bleeding, defined based on hospitalization with those conditions as primary diagnosis, as well as all-cause mortality. Patients were followed from warfarin initiation to the first occurrence of an outcome or censoring. Propensity score weighted time-varying Cox regression was used to evaluate the risk of the clinical events. A total of 127,385 NVAF patients with mean TTR of 51% were included. TTR <65% was observed in 65% of patients. Mean CHA₂DS₂-VAS_C score (SD) was 2.9 (1.5) in the low TTR cohort and 2.7 (1.4) in the high TTR cohort. Patients with TTR <65% had a higher risk for any stroke/SE (HR: 1.57; 95% CI: 1.41–1.75), major bleeding (HR: 2.78; 95% CI: 2.55–3.03) and all-cause mortality (HR: 1.73; 95% CI: 1.67–1.79).

Conclusions: The observed quality of warfarin control in VA EMR suggests room for improvement given the association with elevated risk of adverse clinical outcomes.

Keywords:

• Atrial fibrillation
• hemorrhage
• international normalized ratio
• stroke
• veterans

Transparency

Declaration of funding

This study was sponsored by Bristol-Myers Squibb and Pfizer.

Declaration of financial/other relationships

S.L., Q.S. and L.S. have disclosed that they are employees of Tulane University School of Public Health and Tropical Medicine, and received a research grant in connection with conducting this study. X.L., M.H., K.F. and S.H. have disclosed that they are employees of Bristol-Myers Squibb Company with ownership of stocks in Bristol-Myers Squibb Company. Y.Z. has disclosed that he is an employee of Xavier University of Louisiana. R.H. has disclosed that he is a former employee of Pfizer Inc., with ownership of stocks in Pfizer Inc.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgements

Allison Keshishian, Neel Vaidya, and Michael Moriarty of STATinMED research provided medical writing and editorial support which was funded by Bristol-Myers Squibb and Pfizer.