1
Falls represent the leading cause of traumatic brain injury in adults older than 65, with nearly one third experiencing a fall each year 1 . Evidence suggests that up to 0.5% of anticoagulated patients suffer from ICH annually 3 . Although DOACs have become an increasingly popular alternative to warfarin for anticoagulation, research regarding their safety, speciIically on the outcomes of traumatic ICH is sparse. Moreover, the literature presents conIlicting data comparing outcomes of patients on DOACs or warfarin with ICH. 1,2 Several retrospective studies and a few meta-analyses have examined the incidence of ICH and DOAC use, 3-7 but only a few directly compare the outcomes of ICH coincident with DOAC or warfarin use. 3-6 Furthermore, these studies are mostly cohort trials, containing limited samples of ICH patients; many of these articles contain fewer than ten ICH patients, and most do not consider traumatic ICH separately. 2-7 This study is a retrospective review, considering outcomes of traumatic ICH in DOAC patients, querying Saint Francis Hospital’s Trauma Quality Improvement Program (TQIP) database to bring to light any associations between DOAC use (as compared with warfarin) and mortality, operative intervention, hospital and intensive care unit lengths of stay (HLOS and ICU LOS respectively), transfusion requirements, and discharge to skilled nursing facility (SNF). Compared with warfarin, direct oral anticoagulants are associated with improved patient outcomes in blunt traumatic ICH Acknowledgments The authors, Monica DiFiori, Lilla Kis, and Dr. James Feeney would like to thank Dr. Vijay Jayaraman and Dr. Stephanie Montgomery of Saint Francis Hospital—Trinity Health New England’s Surgery Service Line for their contributions, as well as Elizabeth Santone of University of Connecticut School of Medicine. The authors would also like to thank Dr. Sarah Raskin of Trinity College’s Department of Psychology and Neuroscience Program for her guidance and support. Monica DiFiori ‘16, Lilla Kis ‘18, James Feeney, MD, FACS Trinity College and Saint Francis Hospital—Trinity Health New England, Surgery Service Line, Hartford CT References 1. Centers for Disease Control and Prevention: home and Recreational Safety: Data & Statistics Website http://www.cdc.gov/HomelanfdRecreationalSafety/Falls?adultfalls.html . Accessed February 19, 2016. 2. Alonso A, Bengtson LG, MacLehose RF, Lutsey PL, Chen LY, Lakshminarayan K. Intracranial hemorrhage mortality in atrial fibrillation patients treated with dabigatran or warfarin. Stroke. 2014;45(8):2286-91. 3. Hagii J, Tomita H, Metoki N, Saito S, Shiroto H, Hitomi H, Kamada T, Seino S, Takahashi K, Baba Y, Sasaki S, Uchizawa T, Iwata M, Matsumoto S, Osanai T, Yasujima M, Okumura K. Characteristics of intracerebral hemorrhage during rivaroxaban treatment: comparison with those during warfarin. Stroke. 2014;45(9):2805-7. For a complete list of references, contact Monica DiFiori ([email protected] ) or Lilla Kis ([email protected] ). INTRODUCTION METHODS RESULTS (SD= Standard Deviation, ISS= Injury Severity Score, GCS= Glasgow Coma Score, AIS= Abbreviated Injury Score, MOI= Mechanism of Injury, MVC= Motor Vehicle Crash, CI= Confidence Interval) Table 1: Patient Characteristics, DOACs vs. Warfarin in Traumatic ICH CONCLUSIONS Table 2: Primary and Secondary Outcomes, DOACs vs. Warfarin in Traumatic ICH Compared with warfarin, DOACs are associated with: Improved mortality Decrease in progression to operative intervention Decreased rate of SNF discharge Compared with warfarin, DOACs were not associated with a different ICU LOS nor HLOS Further directions: Although this study has the largest sample size of traumatic ICH associated with DOAC use to date, a large, multicenter trial would result in a more comprehensive patient cohort Randomized controlled trial to better compare the effects of warfarin and DOACs, eliminating any possible correlation between insurance or socioeconomic status and DOAC use and patient outcomes (SD= Standard Deviation, ICU LOS= Intensive Care Unit Length of Stay, HLOS= Hospital Length of Stay, SNF= Skilled Nursing Facility, CI= Confidence Interval) OBJECTIVE The purpose of this study was to elucidate the effects of direct oral anticoagulants (DOACs) in comparison to warfarin in anticoagulated patients sustaining traumatic intracranial hemorrhage (ICH). Patients who presented to the hospital from 6/1/2011-9/1 /2015 with ICH when taking anticoagulants were pulled from the TQIP registry anonymously. Patients were stratiIied based on prescription of DOACs or warfarin. Patient demographics, including age, gender, Glasgow Coma Score (GCS) on arrival, Abbreviated Injury Score (head) (AIS (head)), Mechanism of Injury (MOI) and Injury Severity Score (ISS) were compared between the two groups. Students-t test was used to compare mean age and ISS. Fisher's exact test was used to compare gender and MOI. Mann Whitney U-test was used to compare GCS on admission and AIS (head). Patient outcomes including mortality, need for operative intervention, HLOS, ICU LOS, proportion of patients transfused and discharge to SNF were then compared between the two groups. Fisher's exact test was used to compare mortality, need for operative intervention and SNF discharge. Mann Whitney U-test was used to compare median HLOS and ICU LOS. Fisher’s exact test was used to compare injury characteristics, such as type, location and number of lesions. Direct Oral Anticoagulants Warfarin (p) Age (years) ± SD 77.2 ± 11.2 79.5 ± 13 0.25 Gender (M/ F) ± SD 54.7% Male (95% CI 44.9% to 69.0%) 60.3% Male (95% CI 50.6% to 69.4%) 0.74 Mean ISS ± SD 16.4 ± 8.1 18.2 ± 8.7 0.19 Mean Admission GCS ± SD 14 ± 1.3 13 ± 2.6 0.12 Median AIS (Head) ± SD 3.25 ± 1.2 3.5 ± 1.2 0.07 MOI: Falls 93.4% (95% CI 83.9% to 97.9%) 95.0% (95% CI 88.7% to 98.2%) 1.0 MOI: MVC 6.6% (95% CI 2.1% to 16.1%) 3.0% (95% CI 0.7% to 8.7%) 0.43 MOI: Assault 0.0% (95% CI 0% to 7.1%) 2.0% (95% CI 0.1% to 7.4%) 0.53 Direct Oral Anticoagulants Warfarin (p) Median ICU LOS (days) ± SD 1.4 ± 0.27 1.2 ± 9.2 0.87 Median HLOS (days) ± SD 4 ± 3.5 4 ± 6.9 1.0 Proportion of Patients Transfused ± SD 14.8% (95% CI 7.73% to 26.0%) 21.8% (95% CI 14.8% to 30.9%) 0.31 Number of Units per Patient Transfused ± SD 9 patients/18 units ± 0.88 22 patients/88 Units ± 4.45 0.54 Proportion discharged to SNF ± SD 28.8% (95% CI 3.2% to 18.2%) 39.7% (95% CI 18.8% to 41.5%) 0.03 Operative Intervention 8.2% (95% CI 3.2% to 18.2%) 26.7% (95% CI 19% to 36.1%) 0.02 Mortality 4.9% (95% CI 1.1% to 14.0%) 20.8% (95% CI 15.6% to 31.9%) 0.008 One hundred sixty-two patients met inclusion criteria, 61 in the DOAC group and 101 in the warfarin group. DOAC use was associated with higher mortality (DOAC group 4.9% versus warfarin group 20.8%; p<0.008), a lower rate of operative intervention (DOAC group 8.2% versus warfarin group 26.7%; p=0.02), and a lower observed rate of discharge to SNF (DOAC group 28.8% versus warfarin group 39.7%; p=0.03) (see table 2). Direct Oral Anticoagulants Warfarin (p) SDH (%) 54.1% (95% CI 41.7% to 66.0%) 54.5 % (95% CI 44.8% to 63.8%) 1.0 SAH (%) 41.0% (95% CI 29.5% to 53.5%) 27.7% (95% CI 19.9% to 37.2%) 0.09 IPH (%) 29.5% (95% CI 19.5% to 42.0%) 27.7% (95% CI 19.9% to 37.2%) 0.86 IVH (%) 13.1% (95% CI 7.5% to 21.0%) 12.9% (95% CI 6/5% to 24.1%) 1.0 One lesion (%) 72.1% (95% CI 59.8% to 81.9%) 74.3% (95% CI 64.9% to 81.8%) 0.86 Two lesions (%) 18.0% (95% CI 10.2% to 29.7%) 22.8% (95% CI 15.6% to 31.9%) 0.55 Three or more lesions (%) 9.8% (95% CI 4.3% to 20.2%) 3.0% (95% CI 0.7% to 8.7%) 0.08 Table 3: Injury Characteristics, DOACs vs. Warfarin in Traumatic ICH (SDH= Subdural Hematoma, SAH= Subarachnoid Hemorrhage, IPH= Intraparenchymal Hemorrhage, IVH= Intraventricular Hemorrhage, CI= Confidence Interval)

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Page 1: Compared with warfarin, direct oral anticoagulants …...Falls represent the leading cause of traumatic brain injury in adults older than 65, with nearly one third experiencing a fall

Fallsrepresenttheleadingcauseoftraumaticbraininjuryinadultsolderthan65,withnearlyonethirdexperiencingafalleachyear1.Evidencesuggeststhatup to 0.5% of anticoagulated patients suffer from ICH annually3. AlthoughDOACs have become an increasingly popular alternative to warfarin foranticoagulation,researchregardingtheirsafety,speciIicallyontheoutcomesoftraumatic ICH is sparse. Moreover, the literature presents conIlicting datacomparing outcomes of patients on DOACs or warfarin with ICH.1,2 Severalretrospectivestudiesanda fewmeta-analyseshaveexaminedthe incidenceofICH and DOAC use,3-7 but only a few directly compare the outcomes of ICHcoincidentwithDOACorwarfarinuse.3-6Furthermore,thesestudiesaremostlycohorttrials,containinglimitedsamplesofICHpatients;manyofthesearticlescontain fewer than ten ICH patients, andmost do not consider traumatic ICHseparately.2-7 This study is a retrospective review, considering outcomes oftraumatic ICH in DOAC patients, querying Saint Francis Hospital’s TraumaQuality Improvement Program (TQIP) database to bring to light anyassociations between DOAC use (as compared with warfarin) and mortality,operative intervention, hospital and intensive care unit lengths of stay (HLOSand ICU LOS respectively), transfusion requirements, and discharge to skillednursingfacility(SNF).

Compared with warfarin, direct oral anticoagulants are associated with improved patient outcomes in blunt traumatic ICH

Acknowledgments Theauthors,MonicaDiFiori,LillaKis,andDr.JamesFeeneywouldliketothankDr.VijayJayaramanandDr. StephanieMontgomery of Saint Francis Hospital—Trinity Health New England’s Surgery ServiceLine for their contributions, as well as Elizabeth Santone of University of Connecticut School ofMedicine. The authorswould also like to thank Dr. Sarah Raskin of Trinity College’s Department ofPsychologyandNeuroscienceProgramforherguidanceandsupport.

Monica DiFiori ‘16, Lilla Kis ‘18, James Feeney, MD, FACS Trinity College and Saint Francis Hospital—Trinity Health New England, Surgery Service Line, Hartford CT

References 1. Centers for Disease Control and Prevention: home and Recreational Safety: Data & Statistics Website

http://www.cdc.gov/HomelanfdRecreationalSafety/Falls?adultfalls.html. Accessed February 19, 2016.

2. Alonso A, Bengtson LG, MacLehose RF, Lutsey PL, Chen LY, Lakshminarayan K. Intracranial hemorrhage mortality in atrial fibrillation patients treated with dabigatran or warfarin. Stroke. 2014;45(8):2286-91.

3. Hagii J, Tomita H, Metoki N, Saito S, Shiroto H, Hitomi H, Kamada T, Seino S, Takahashi K, Baba Y, Sasaki S, Uchizawa T, Iwata M, Matsumoto S, Osanai T, Yasujima M, Okumura K. Characteristics of intracerebral hemorrhage during rivaroxaban treatment: comparison with those during warfarin. Stroke. 2014;45(9):2805-7.

For a complete list of references, contact Monica DiFiori ([email protected]) or Lilla Kis ([email protected]).

INTRODUCTION

METHODS

RESULTS

(SD= Standard Deviation, ISS= Injury Severity Score, GCS= Glasgow Coma Score, AIS= Abbreviated Injury Score, MOI= Mechanism of Injury, MVC= Motor Vehicle Crash, CI= Confidence Interval)

Table1:PatientCharacteristics,DOACsvs.WarfarininTraumaticICH

CONCLUSIONS

Table2:PrimaryandSecondaryOutcomes,DOACsvs.WarfarininTraumaticICH

•  Comparedwithwarfarin,DOACsareassociatedwith:•  Improvedmortality•  Decreaseinprogressiontooperativeintervention•  DecreasedrateofSNFdischarge

•  Comparedwithwarfarin,DOACswerenotassociatedwithadifferentICULOSnorHLOS

•  Furtherdirections:•  AlthoughthisstudyhasthelargestsamplesizeoftraumaticICHassociatedwithDOACusetodate,alarge,multicentertrialwouldresultinamorecomprehensivepatientcohort

•  RandomizedcontrolledtrialtobettercomparetheeffectsofwarfarinandDOACs,eliminatinganypossiblecorrelationbetweeninsuranceorsocioeconomicstatusandDOACuseandpatientoutcomes

(SD= Standard Deviation, ICU LOS= Intensive Care Unit Length of Stay, HLOS= Hospital Length of Stay, SNF= Skilled Nursing Facility, CI= Confidence Interval)

OBJECTIVE

The purpose of this study was to elucidate the effects of direct oralanticoagulants (DOACs) in comparison to warfarin in anticoagulated patientssustainingtraumaticintracranialhemorrhage(ICH).

Patientswhopresentedtothehospital

from6/1/2011-9/1/2015withICHwhentaking

anticoagulantswerepulledfromtheTQIP

registryanonymously.

PatientswerestratiIiedbasedon

prescriptionofDOACsorwarfarin.

Patientdemographics,includingage,gender,GlasgowComaScore(GCS)onarrival,AbbreviatedInjuryScore(head)(AIS

(head)),MechanismofInjury(MOI)and

InjurySeverityScore(ISS)werecomparedbetweenthetwo

groups.Students-ttestwasusedtocomparemeanageandISS.

Fisher'sexacttestwasusedtocompare

genderandMOI.MannWhitneyU-testwasusedtocompareGCSonadmissionandAIS

(head).

Patientoutcomesincludingmortality,needforoperativeintervention,HLOS,ICULOS,proportion

ofpatientstransfusedanddischargetoSNF

werethencomparedbetweenthetwo

groups.Fisher'sexacttestwasusedto

comparemortality,needforoperativeinterventionandSNFdischarge.Mann

WhitneyU-testwasusedtocomparemedianHLOSand

ICULOS.

Fisher’sexacttestwasusedtocompareinjury

characteristics,suchastype,locationandnumberoflesions.

DirectOralAnticoagulants Warfarin (p)

Age(years)±SD 77.2±11.2 79.5±13 0.25

Gender(M/F)±SD

54.7%Male(95%CI44.9%to69.0%)

60.3%Male(95%CI50.6%to69.4%) 0.74

MeanISS±SD 16.4±8.1 18.2±8.7 0.19

MeanAdmissionGCS±SD

14±1.3 13±2.6 0.12

MedianAIS(Head)±SD 3.25±1.2 3.5±1.2 0.07

MOI:Falls 93.4%(95%CI83.9%to97.9%)

95.0%(95%CI88.7%to98.2%) 1.0

MOI:MVC 6.6%(95%CI2.1%to16.1%)

3.0%(95%CI0.7%to8.7%) 0.43

MOI:Assault 0.0%(95%CI0%to7.1%)

2.0%(95%CI0.1%to7.4%) 0.53

DirectOralAnticoagulants Warfarin (p)

MedianICULOS(days)±SD 1.4±0.27 1.2±9.2 0.87

MedianHLOS(days)±SD 4±3.5 4±6.9 1.0

ProportionofPatients

Transfused±SD

14.8%(95%CI7.73%to26.0%)

21.8%(95%CI14.8%to30.9%) 0.31

NumberofUnitsperPatient

Transfused±SD9patients/18units±0.88 22patients/88Units±4.45 0.54

ProportiondischargedtoSNF

±SD

28.8%(95%CI3.2%to18.2%)

39.7%(95%CI18.8%to41.5%) 0.03

OperativeIntervention

8.2%(95%CI3.2%to18.2%)

26.7%(95%CI19%to36.1%) 0.02

Mortality 4.9%(95%CI1.1%to14.0%)

20.8%(95%CI15.6%to31.9%) 0.008

Onehundredsixty-twopatientsmetinclusioncriteria,61intheDOACgroupand101inthewarfarin group. DOAC usewas associatedwith highermortality (DOAC group 4.9% versuswarfarin group20.8%;p<0.008), a lower rate of operative intervention (DOACgroup8.2%versuswarfaringroup26.7%;p=0.02),andalowerobservedrateofdischargetoSNF(DOACgroup28.8%versuswarfaringroup39.7%;p=0.03)(seetable2).

DirectOralAnticoagulants Warfarin (p)

SDH(%) 54.1%(95%CI41.7%to66.0%)

54.5%(95%CI44.8%to63.8%) 1.0

SAH(%) 41.0%(95%CI29.5%to53.5%)

27.7%(95%CI19.9%to37.2%) 0.09

IPH(%) 29.5%(95%CI19.5%to42.0%)

27.7%(95%CI19.9%to37.2%) 0.86

IVH(%) 13.1%(95%CI7.5%to21.0%)

12.9%(95%CI6/5%to24.1%) 1.0

Onelesion(%)

72.1%(95%CI59.8%to81.9%)

74.3%(95%CI64.9%to81.8%) 0.86

Twolesions(%)

18.0%(95%CI10.2%to29.7%)

22.8%(95%CI15.6%to31.9%) 0.55

Threeormorelesions(%)

9.8%(95%CI4.3%to20.2%)

3.0%(95%CI0.7%to8.7%) 0.08

Table3:InjuryCharacteristics,DOACsvs.WarfarininTraumaticICH

(SDH= Subdural Hematoma, SAH= Subarachnoid Hemorrhage, IPH= Intraparenchymal Hemorrhage, IVH= Intraventricular Hemorrhage, CI= Confidence Interval)