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It has long been understood that anticoagulant-related intracerebral hemorrhage (ICH) is associated with worse outcomes than non-anticoagulant-related ICH. Recently, non–vitamin K antagonist oral anticoagulants (NOACs) have become a common alternative to warfarin in patients with atrial fibrillation. While NOACs have lower rates overall of ICH compared with warfarin across multiple trials, it remains unknown whether ICH in the setting of NOACs has an outcome different from warfarin-associated ICH. In a recent study, Inohara and colleagues (2018) aimed to examine this issue using a large retrospective cohort approach.

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The authors used data from the Get With the Guidelines-Stroke registry, a national voluntary registry of hospitals in the United States. All patients who experienced ICH between October 2013 and December 2016 were identified in the registry, and preceding use of warfarin, NOACs, or antiplatelet drugs within 7 days of hospitalization was recorded. Excluded patients were those taking more than one anticoagulant, those with prosthetic heart valves, and those taking three or more antiplatelet medications. The primary outcome examined was in-hospital mortality.

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A total of 141,311 patients from 1662 hospitals with ICH were included in the final analysis with a mean age of 68.3 years and a slight male predominance (51.9%). Of these patients, 15,036 (10.6%) had received warfarin prior to the ICH and 4918 (3.5%) were taking a NOAC. The severity of ICH at admission was not significantly different among the warfarin group, the NOAC group, and a group taking antiplatelet medications.

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Patients taking any form of anticoagulant had a higher risk of in-hospital mortality than those who were not. Patients in the NOAC group had a significantly lower risk of in-hospital mortality than those in the warfarin group (adjusted risk difference, –5.7%; adjusted odds ratio, 0.75; 95% confidence interval, 0.69–0.81). Patients in the NOAC group were also more likely to be discharged home and to have better functional outcomes at discharge compared with patients taking warfarin. These findings persisted when limited to those without previous use of antiplatelet agents and when performing adjustment based on initial stroke scale score.

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The patients in the warfarin group also underwent additional analyses based on their presenting international normalized ratio (INR). Unadjusted mortality was higher in these patients with supratherapeutic INR (37.9%) than in those with therapeutic INR (32.4%) or subtherapeutic INR (25.0%). In-hospital mortality still significantly favored those in the NOAC group when compared with both the supratherapeutic and therapeutic groups, although there was no significant difference found in comparison with the subtherapeutic group.

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This study, likely the largest ever examining anticoagulant-related ICH, demonstrates yet another reason for clinicians to consider NOAC use over warfarin. Not only is there a lower risk of ICH in patients treated with NOACs compared with warfarin, but when ICH occurs, there are fewer consequences with demonstrated decreased rates of mortality and better functional outcomes at discharge. This information is reasonable to discuss with patients who are considering various forms of anticoagulation for atrial fibrillation. It should also be noted that the time frame of these data mainly involved a period in which there were no reversal agents commonly available for NOACs—an advance that in the coming years will presumably lead to even better outcomes for NOAC-associated ICH.

Reference

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Inohara  T  et al: Association of intracerebral hemorrhage among patients taking non–vitamin k antagonist vs vitamin k antagonist oral anticoagulants with in-hospital mortality. JAMA, 2018.
[PubMed: 29372247]