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  • Intraparenchymal Hemorrhage After Direct Oral Anticoagulant or Vitamin K Antagonist Therapy: A meta-analysis of clinical outcomes

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    Aislyn DiRisio BS; Maya Harary BA; Ivo S Muskens BSc; Ismaeel Yunusa Pharm.D.; William B. Gormley MD; Linda S Aglio MD; Timothy R. Smith MD PhD MPH; Jean M Connors MD; Rania A Mekary PhD; Marike Broekman MD, PhD, JD

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    Meeting: Congress of Neurological Surgeons 2017 Annual Meeting - Late Breaking Science

    Introduction: Direct Oral Anticoagulants (DOAC) are increasingly used as an alternative to vitamin-K antagonists (VKA) such as warfarin for anticoagulation and have shown lower rates of intracranial hemorrhage in several randomized clinical trials. Little is known about the outcomes of the intraparenchymal hemorrhages (IPH) associated with DOACs. Given the lack of standardized reversal strategies and lack of information on outcomes following DOAC-associated IPH, the aim of this meta-analysis was to compare 1) mortality; 2) hematoma volume, and 3) risk of hematoma expansion in patients who developed an IPH on DOACs versus VKA.

    Methods: A meta-analysis of the literature through December 2016 was conducted using PubMed, EMBASE and Cochrane databases in accordance with the PRISMA guidelines. Studies were selected that reported on mortality, hematoma expansion, and hematoma volume in DOAC-associated IPH. Pooled risk ratios (RR) were calculated for mortality and hematoma expansion and pooled mean difference (MD) was calculated for hematoma volume (ml) using random-effect (RE) and fixed-effect (FE) models.

    Results: 15 studies reporting on 2,124 patients were included in the systematic review. Of these studies, eight compared DOAC-IPH to VKA-IPH and were pooled quantitatively in the meta-analysis. DOAC-IPH was not associated with increased mortality (RE and FE: RR: 1.07; 95%-CI: 0.89;1.28, I2=0%, p-heterogeneity=0.29; 7 studies) or hematoma expansion (RE and FE: RR: 0.97; 95%-CI: 0.77;1.21, I2=0%, p-heterogeneity=0.48; 4 studies) compared to VKA-IPH. The hematoma volume of DOAC- IPH was smaller than VKA-IPH (RE: MD: -8.83ml; 95%-CI: -17.00; - 0.67, FE: MD: -6.48ml; 95%-CI: -9.85; -3.10; 5 studies), but with considerable heterogeneity that could not be alleviated (I2=79.1%, p-heterogeneity<0.01). No significant publication bias was identified for all outcomes (all p>0.05).

    Conclusions: DOAC-IPH was not associated with increased mortality or hematoma expansion compared to VKA-IPH and may be associated with a smaller hematoma volume.

    Patient Care: Little is known about DOAC-associated IPH, and this research helps us understand the risks faced by these patients in comparison to VKA-associated IPH patients.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) understand concerns in intraparenchymal hemorrhage in patients on chronic anticoagulation, 2) understand the relative risk of mortality in DOAC-associated IPH versus VKA-associated IPH, 3) understand the relative IPH volume and risk for IPH expansion between patients on DOACs versus VKAs.


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