title: Relationship Between Anticoagulation Intensity and Thrombotic or Bleeding Outcomes Among Outpatients With Continuous-Flow Left Ventricular Assist Devices.
abstract: We evaluated thrombotic and bleeding outcomes in patients with continuous-flow left ventricular assist devices (CF-LVADs), stratified by anticoagulation intensity. Previous studies of outpatients with CF-LVADs have suggested that target international normalized ratio (INR) values <2.5 (range, 2-3) may be used. However, recent studies reported an increase in pump thrombosis among CF-LVADs, especially within the first 6 months of implant.
  
  
  
  We retrospectively reviewed 249 outpatients at our center who received a CF-LVAD between January 2005 and August 2013. Using Poisson models, we analyzed their 10 927 INRs to determine INR-specific rates of thrombotic (ischemic stroke and suspected pump thrombosis) and hemorrhagic (gastrointestinal bleeding and hemorrhagic stroke) events occurring outside of the hospital. In multivariate analyses, we adjusted for age, sex, atrial fibrillation, coronary disease, and LVAD type as time-dependent Cox proportional hazard models. During a mean follow-up of 17.6±13.6 months, thrombotic events occurred in 46 outpatients. The highest event rate (0.40 thrombotic events per patient-year) was in the INR range of <1.5, but INR values of 1.5 to 1.99 also had high rates (0.16 thrombotic events per patient-year). INR was inversely associated with thrombotic events (hazard ratio, 0.40; 95% confidence interval, 0.22-0.72; P=0.002). The optimal INR based on weighted mortality of thrombotic and bleeding events was 2.6.
  
  
  
  INR is inversely related to thrombotic events occurring outside of the hospital among patients supported with CF-LVADs. INR values <2.0 increase the rate of thrombotic events occurring outside of the hospital among patients supported with CF-LVADs.
authors.affiliation: From the Division of Cardiology, Department of Medicine (M.E.N., S.J.L., E.N., J.M.V., G.A.E.) and Department of Medicine (D.S.R., B.F.G.), Washington University School of Medicine, St. Louis, MO.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Nassif
authors.affiliation: From the Division of Cardiology, Department of Medicine (M.E.N., S.J.L., E.N., J.M.V., G.A.E.) and Department of Medicine (D.S.R., B.F.G.), Washington University School of Medicine, St. Louis, MO. slarue@dom.wustl.edu.
authors.forename: Shane J
authors.initials: SJ
authors.lastname: LaRue
authors.affiliation: From the Division of Cardiology, Department of Medicine (M.E.N., S.J.L., E.N., J.M.V., G.A.E.) and Department of Medicine (D.S.R., B.F.G.), Washington University School of Medicine, St. Louis, MO.
authors.forename: David S
authors.initials: DS
authors.lastname: Raymer
authors.affiliation: From the Division of Cardiology, Department of Medicine (M.E.N., S.J.L., E.N., J.M.V., G.A.E.) and Department of Medicine (D.S.R., B.F.G.), Washington University School of Medicine, St. Louis, MO.
authors.forename: Eric
authors.initials: E
authors.lastname: Novak
authors.affiliation: From the Division of Cardiology, Department of Medicine (M.E.N., S.J.L., E.N., J.M.V., G.A.E.) and Department of Medicine (D.S.R., B.F.G.), Washington University School of Medicine, St. Louis, MO.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Vader
authors.affiliation: From the Division of Cardiology, Department of Medicine (M.E.N., S.J.L., E.N., J.M.V., G.A.E.) and Department of Medicine (D.S.R., B.F.G.), Washington University School of Medicine, St. Louis, MO.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Ewald
authors.affiliation: From the Division of Cardiology, Department of Medicine (M.E.N., S.J.L., E.N., J.M.V., G.A.E.) and Department of Medicine (D.S.R., B.F.G.), Washington University School of Medicine, St. Louis, MO.
authors.forename: Brian F
authors.initials: BF
authors.lastname: Gage
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001777:Blood Coagulation / Q000187:drug effects*; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D006333:Heart Failure / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D006353:Heart-Assist Devices / Q000009:adverse effects*; D006801:Humans; D019934:International Normalized Ratio; D020300:Intracranial Hemorrhages / Q000139:chemically induced; D020767:Intracranial Thrombosis / Q000097:blood / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D008923:Missouri; D015999:Multivariate Analysis; D010045:Outpatients; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011474:Prosthesis Design; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left; D055815:Young Adult
chemical_list: D000925:Anticoagulants
keywords: atrial fibrillation; follow-up studies; hemorrhage; international normalized ratio stroke