Editor’s Note: Commentary based on Albrecht JS, Liu X, Baumgarten M, et al. Benefits and risks of anticoagulation resumption following traumatic brain injury. JAMA Intern Med 2014; 174:1244-51.

Background

Anticoagulant therapy can reduce the risk of thrombotic events including venous thromboembolism and stroke after traumatic brain injury (TBI), but it carries a higher risk of bleeding.¹ Balancing the risk-benefit in elderly patients with TBI is particularly challenging, as older patients have both increased bleeding risk and benefit with anticoagulant therapy. Current clinical guidelines do not provide clear guidelines regarding the decision to resume long-term anticoagulant therapy in older patients after TBI.^2,3

Methods

A retrospective analysis from administrative data for Medicare beneficiaries who were aged at least 65 years, hospitalized for TBI, and were prescribed warfarin in the month prior to TBI was conducted by Albrecht JS et al.⁴ to evaluate the risk of thrombotic and hemorrhagic events associated with warfarin therapy resumption after TBI.

The primary exposure was warfarin use in each 30-day period following discharge after hospitalization. The primary endpoints were hemorrhagic and thrombotic events. Hemorrhagic events included hemorrhagic stroke, upper gastrointestinal bleeding, adrenal hemorrhage, and other hemorrhage. Thrombotic events included ischemic stroke, pulmonary embolism, deep venous thrombosis, and myocardial infarction.⁴

Results

The 10,782 patients with TBI were more frequently female (64%) and white (92%), with a mean (SD) age of 81.3 (7.3) years, and a high prevalence of comorbidity (82% had atrial fibrillation).⁴

Following hospital discharge, 55% had used warfarin during at least one or more 30-day period over the subsequent 12 months. Warfarin use in the prior period was associated with decreased risk of thrombotic events (relative risk [RR], 0.77; 95% confidence interval [CI], 0.67-0.88) and increased risk of hemorrhagic events (RR, 1.51; 95% CI, 1.29-1.78). Warfarin use in the prior period reduced the risk of the composite outcome of hemorrhagic or ischemic stroke (RR, 0.83; 95% CI, 0.72-0.96) in the following period. The interaction between period and lagged warfarin use was not statistically significant.⁴

Conclusion

Despite an increased risk of hemorrhage, there is a net benefit for most patients receiving anticoagulation therapy, in terms of a reduction in risk of stroke, from warfarin therapy resumption following discharge after hospitalization for TBI.⁴

Commentary/Perspective

Anticoagulation therapy in patients with atrial fibrillation is underutilized in clinical practice,⁵ primarily due to concerns about the risk of bleeding – a risk that has even greater consequences in patients with recent TBI. In this study, 82% of the participants taking warfarin prior to TBI had atrial fibrillation, but only 55% of participants resumed warfarin use for at least one month in the year following TBI.⁴ The most common barriers were fear of bleeding risk in older patients, the presence of Alzheimer disease, and a perceived contraindication to resume anticoagulation in patients with more severe injury.

The key finding of this study is that warfarin use after TBI decreased the risk of thrombotic events, although the risk of hemorrhage was increased. Interestingly, this study did not demonstrate an increase in hemorrhagic stroke, the most feared type of bleeding, after resumption of warfarin therapy following TBI. The findings did not change significantly over time, suggesting that most patients without absolute contraindications would benefit from resuming warfarin therapy immediately following discharge after hospitalization for TBI to reduce the risk of stroke.⁴

These findings should help guide clinicians and patients in making treatment decisions regarding the benefit and risk of anticoagulant therapy after traumatic injury.

There are several limitations worth noting. This study did not directly assess TBI severity, which could strongly affect the risk of hemorrhage events and physician’s decision on anticoagulant resumption. Further analysis stratified by the severity of TBI would be helpful. The data were from an observational cohort and treatment was neither randomized nor blinded. In the future, a double-blind, randomized controlled trial would be helpful, as well as a study evaluating the timing of resumption of anticoagulation therapy (early vs. late resumption) after TBI.

References

1. Levy  AS, Salottolo  K, Bar-Or  R,  et al. Pharmacologic thromboprophylaxis is a risk factor for hemorrhage progression in a subset of patients with traumatic brain injury. J Trauma 2010;68:886-94.
2. Rogers  FB, Cipolle  MD, Velmahos  G, Rozycki  G, Luchette  FA. Practice management guidelines for the prevention of venous thromboembolism in trauma patients: the EAST practice management guidelines work group. J Trauma 2002;53:142-64.
3. Brain Trauma Foundation; American Association of Neurological Surgeons; Congress of Neurological Surgeons; Joint Section on Neurotrauma and Critical Care, AANS/CNS; et al. Guidelines for the management of severe traumatic brain injury. V. deep vein thrombosis prophylaxis. J Neurotrauma 2007;24 Suppl 1:S32-6.
4. Albrecht JS, Liu X, Baumgarten M, et al. Benefits and risks of anticoagulation resumption following traumatic brain injury. JAMA Intern Med 2014; 174:1244-51.
5. Agarwal S, Bennett D, Smith DJ. Predictors of warfarin use in atrial fibrillation patients in the inpatient setting. Am J Cardiovasc Drugs 2010;10:37-48.

Keywords: Aged, Alzheimer Disease, Anticoagulants, Atrial Fibrillation, Brain Injuries, Comorbidity, Confidence Intervals, Double-Blind Method, Fear, Female, Hemorrhage, Hospitalization, Medicare, Myocardial Infarction, Prevalence, Pulmonary Embolism, Retrospective Studies, Risk, Stroke, Venous Thromboembolism, Venous Thrombosis, Warfarin

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