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Thromb Haemost 2022; 122(03): 386-393
DOI: 10.1055/a-1508-8187
Stroke, Systemic or Venous Thromboembolism

Using a Simple Prescription Gap to Determine Warfarin Discontinuation Can Lead to Substantial Misclassification

Kueiyu Joshua Lin
1   Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
2   Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States
,
Sebastian Schneeweiss
1   Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
,
Ajinkya Pawar 
1   Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
,
Daniel E. Singer
2   Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States
,
Jun Liu
1   Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
,
Joshua J. Gagne
1   Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States
› Author Affiliations Funding This project was supported by NIH Grant 1RF1AG063381-01.
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Abstract

Background Warfarin remains widely used and a key comparator in studies of other direct oral anticoagulants. As longer-than-needed warfarin prescriptions are often provided to allow for dosing adjustments according to international normalized ratios (INRs), the common practice of using a short allowable gap between dispensings to define warfarin discontinuation may lead to substantial misclassification of warfarin exposure. We aimed to quantify such misclassification and determine the optimal algorithm to define warfarin discontinuation.

Methods We linked Medicare claims data from 2007 to 2014 with a multicenter electronic health records system. The study cohort comprised patients ≥65 years with atrial fibrillation and venous thromboembolism initiating warfarin. We compared results when defining warfarin discontinuation by (1) different gaps (3, 7, 14, 30, and 60 days) between dispensings and (2) having a gap ≤60 days or bridging larger gaps if there was INR ordering at least every 42 days (60_INR). Discontinuation was considered misclassified if there was an INR ≥2 within 7 days after the discontinuation date.

Results Among 3,229 patients, a shorter gap resulted in a shorter mean follow-up time (82, 95, 117, 159, 196, and 259 days for gaps of 3, 7, 14, 30, 60, and 60_INR, respectively; p < 0.001). Incorporating INR (60_INR) can reduce misclassification of warfarin discontinuation from 68 to 4% (p < 0.001). The on-treatment risk estimation of clinical endpoints varied significantly by discontinuation definitions.

Conclusion Using a short gap between warfarin dispensings to define discontinuation may lead to substantial misclassification, which can be improved by incorporating intervening INR codes.

Keywords

warfarin discontinuation - stroke prevention - exposure misclassification

Supplementary Material



Publication History

Received: 10 August 2020

Accepted: 12 May 2021

Accepted Manuscript online:
13 May 2021

Article published online:
02 July 2021

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