Risk of recurrent venous thromboembolism among deep vein thrombosis and pulmonary embolism patients treated with warfarin

Abstract

Objective:

Guidelines for warfarin treatment of venous thromboembolism (VTE) recommend targeting an international normalized ratio (INR) level of 2–3. This study examines the association between INR levels and VTE recurrence among warfarin-treated patients.

Methods:

A retrospective cohort study in the MedMining electronic health record database included adults treated with warfarin for VTE in 2004–2011. INR levels during warfarin use were categorized as below therapeutic range (<2), in range (2–3), or above range (>3), with time in each category estimated using the Rosendaal method. Recurrent VTE was noted from 30 days after the initial VTE to end of follow-up, which ranged up to 8 years. The incidence of recurrent VTE was calculated, and association with time-varying INR levels estimated using Cox models.

Results:

Of 1753 qualifying patients, 867 had deep vein thrombosis, and 886 had pulmonary embolism. Mean age was 58 years, and 50.7% were female. Across all follow-up time, VTE recurrences were observed in 134 (7.6%) patients, at a rate of 3.2 (95% confidence interval [CI]: 0.7–9.1) events per 100 person-years. The risk of VTE recurrence was greater during time spent with INR <2 than with INR in the therapeutic range (hazard ratio [HR]: 3.37; 95% CI: 2.16–5.27). Low platelet counts also predicted greater risk of VTE recurrence (HR: 2.13; 95% CI: 1.24–3.67).

Limitations:

Exposure to warfarin and other anticoagulants was estimated based on prescription data and may be inaccurate. The study data include care within a single health system; thus, care received outside of the health system may be missing, and results may not be generalizable to the broader US population.

Conclusions:

Approximately 8% of patients experienced a recurrent VTE during follow-up. Subtherapeutic INR levels were associated with a more than three-fold increased risk of VTE recurrence.

Keywords: :

• Deep vein thrombosis
• International normalized ratio
• Pulmonary embolism
• Venous thromboembolism
• Warfarin

Transparency

Declaration of funding

Janssen Scientific Affairs LLC, Raritan, NJ, USA provided the funding for this study.

Declaration of financial/other relationships

M.A.E. has disclosed that he has served on speakers bureaus for Janssen Scientific Affairs LLC and Roche Pharmaceuticals. E.A.N. has disclosed that she was a consultant to, received grant support from, and served on a speaker forum for Janssen Scientific Affairs LLC. J.R.S. and B.K.B. have disclosed that they are employees of Janssen Scientific Affairs LLC and shareholders of Johnson & Johnson. B.L.N. and B.R.M. have disclosed that they are employees of Evidera, a consultancy that received funding from Janssen Scientific Affairs LLC for the study on which this manuscript is based.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors acknowledge Chameleon Communications International for editorial review, with funding from Janssen Scientific Affairs LLC.