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Literature Review

By Currents Editor posted 02-08-2019 11:50


Kyle_Hobbs_Headshot.jpgSara_Stern-Nezer.jpgBy Kyle Hobbs, MD, and Sara Stern-Nezer, MD

Due to their efficacy and favorable rates of complications when compared to vitamin K antagonist therapy, direct or novel oral anticoagulant (NOAC/DOAC) use is now widespread, and reversal agents exist for many of these medications. The studies reviewed below analyzed how different disease outcomes (traumatic brain injury and subdural hematoma) were affected by the use of DOAC therapy.

The novel oral anticoagulants have worse outcomes compared with warfarin in patients with intracranial hemorrhage after TBI.

J Trauma Acute Care Surg 2018; 85: 915-20.

Summary: NOAC use in trauma patients is becoming increasingly prevalent, but with limited understanding of effect on outcomes in the TBI population. This single-center observational analysis of prospectively collected data included all adult trauma patients admitted with a diagnosis of traumatic brain injury (TBI) who had intracerebral hemorrhage (ICH) on initial head CT and were taking preinjury oral anticoagulants (warfarin, direct thrombin inhibitors, or Xa inhibitors). Patients were stratified by type of preinjury oral anticoagulant (warfarin vs NOAC) and by severity of TBI. Propensity score matching was performed for the two cohorts in a 1:2 ratio (NOAC:warfarin). NOAC patients had a higher Injury Severity Score (ISS) on admission. After propensity score matching (70 NOACs, 140 warfarin), mean age was 58.7 + 15.2 years, 67.6% male, median GCS 14 (IQR, 8-15), with falls being the most common mechanism of injury. In the NOAC group, 54% were taking oral Xa inhibitors and 46% were taking dabigatran (direct thrombin inhibitor). There were no differences in demographic characteristics, comorbidities, mechanism of injury, GCS on admission, or rate of epidural, subdural, or subarachnoid hemorrhage. 58% of patients were taking antiplatelet agents in addition to their anticoagulant, evenly matched between the two groups. NOAC patients had higher rates of progression of ICH on repeat CT scan (p=0.03), neurosurgical intervention (p=0.04), longer ICU length of stay (p=0.04), and higher mortality (p=0.04). There were no differences in hospital length of stay or discharge GOS-E. Subanalysis showed that mild and moderate TBI patients were significantly more likely to be discharged to rehab/SNF, and had higher mortality and need for neurosurgical intervention, while these differences were not significant for patients with severe TBI.

Commentary: This study showed worse outcomes in TBI patients who were being treated with NOAC therapy when compared to patients taking warfarin. This analysis has limited generalizability as it was a single center study, and the reason for anticoagulation was not included; however, the propensity score matching did attempt to account for confounding variables between groups. Data was lacking on the reversal agents used in both the NOAC and warfarin groups, which likely had an impact on progression of hemorrhage, as did the relatively high rate of concomitant antiplatelet use. Further study in this population is needed, particularly with the approval of adexanet alfa.

Improved outcomes in patients taking DOACs over VKA in acute subdural hemorrhage.

Neurocrit Care 2018; epub ahead of print.

Summary: While therapy with vitamin K antagonists (VKA) has been shown to worsen outcomes in acute SDH, there is little data on the effect of DOAC therapy in this population. This single-center retrospective analysis included all patients treated for acute SDH who were on DOAC or VKA therapy on admission. Patients with purely chronic SDH were excluded, but acute on chronic SDH was allowed. The neurosurgical consultant determined whether to administer pro-hemostatic substances and/or perform operative intervention. Prothrombin complex concentrate (PCC) was administered in the majority of cases, as well as IV phytomenadione if patients were on VKA therapy. 128 patients were included (65 DOAC, 63 VKA). PCC was administered more frequently in the VKA group and at higher mean dose. Patients with VKA had a lower GCS score on admission, fewer VKA patients had GCS 13-15, and more VKA patients were intubated prior to hospital arrival. Recent trauma was reported more often in the DOAC group (89% vs 60%, p<0.001). There were no significant differences in the rate of rehemorrhage in the DOAC group, and overall 30-day mortality was the same for DOAC vs VKA (26% vs 27%, p=1.00). Rate of neurosurgical procedures was not significantly different between groups. DOAC patients had significantly higher Glasgow Outcome Scores (GOS) at hospital discharge, and mean hospital length of stay was shorter (5.9 vs 7.2 days, p=0.024). Only 7 DOAC patients were taking dabigatran, of which 4 (57%) received idarucizumab, with no deaths at 30 days. One patient on apixaban who received PCC on admission died of an ST-elevation MI 5 days later.

Commentary: This study suggests that patients on preinjury DOAC therapy may have improved outcomes compared to those taking VKAs in the event of acute subdural hemorrhage. While mortality was the same between groups, the DOAC group had shorter hospital LOS and better 30-day outcomes, as well as similar rates of neurosurgical intervention and rehemorrhage compared to warfarin. This study is limited in its small size and that it was conducted at a single center. In addition, there was imbalance between groups on admission, with higher mean admission GCS scores in the DOAC group and lower rates of prehospital intubation. It is possible, however, that the benefit seen from being on DOAC therapy would have been higher with andexanet alfa for Xa inhibitor reversal, as only 58% DOAC patients received PCC in this study. Whether andexanet alfa use translates to better clinical outcomes remains to be seen.

#LiteratureWatch #KyleHobbs #SaraStern-Nezer #December2018

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