title: Relationship between time spent at extreme International Normalized Ratios and time in therapeutic range with bleeding and thrombosis in warfarin-treated patients.
abstract: OBJECTIVE
  The relationship between the time spent at extreme International Normalized Ratios (INRs) and the time in the therapeutic range (TTR) with bleeding and thrombosis in warfarin-treated patients was examined.
  
  
  METHODS
  Consecutive patients treated with warfarin for atrial fibrillation or for venous thrombosis who were managed by the anticoagulation management service or adult internal medicine clinic of a large, tertiary care, integrated health system between June 1, 2011, and October 9, 2012, were eligible for study inclusion. Data collected for the outcomes analysis included INRs and dates; current use of aspirin, clopidogrel, prasugrel, ticagrelor, ticlopidine, or nonsteroidal antiinflammatory drugs; and any clinically significant bleeding or thrombosis events identified.
  
  
  RESULTS
  In the 837 patients who met the inclusion criteria, 636.5 patient-years of therapy were provided, of which 14.4 patient-years (2.26% of time) were spent at INRs of <1.5; 2.9 patient-years of therapy (0.45% of time) were spent at INRs of >4.5. The patient population had a mean individual TTR of 65%. The percentage of time at an INR of >4.5 was positively associated with an increased risk of major bleeding (p = 0.0085). The percentage of time spent with an INR of <1.5 was not associated with a significant increase in the risk of thrombosis.
  
  
  CONCLUSIONS
  The percentage of time spent with an INR of >4.5 was associated with an increased risk of major bleeding in patients receiving warfarin for atrial fibrillation or for venous thrombosis at two outpatient clinics. The relationships between thrombosis risk and the TTR or the time spent at an INR of <1.5 were not significant, but the thromboembolic event rate was unusually low, as was the time spent at an INR of <1.5.
authors.affiliation: Ashley L. Barta, Pharm.D., is Clinical Pharmacist, Sanford USD Medical Center, Sioux Falls, SD; when this project was conducted she was Postgraduate Year 1 Resident, Sanford USD Medical Center. Edith A. Nutescu, Pharm.D., is Associate Professor, Department of Pharmacy Systems Outcomes and Policy, and Co-Director, Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago College of Pharmacy, Chicago. Paul A. Thompson, Ph.D., is Director, Methodology and Data Analysis Center, and Professor, Department of Pediatrics, Sanford School of Medicine, Sanford Research, Sioux Falls. Henry I. Bussey, Pharm.D., is President and Senior Editor, ClotCare.org, San Antonio, TX, and President, Genesis Clinical Research, San Antonio. Michael P. Gulseth, Pharm.D., BCPS, FASHP, is Program Director for Anticoagulation Services, Sanford USD Medical Center, and Adjunct Assistant Professor, College of Pharmacy, South Dakota State University, Sioux Falls.
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Barta
authors.affiliation: Ashley L. Barta, Pharm.D., is Clinical Pharmacist, Sanford USD Medical Center, Sioux Falls, SD; when this project was conducted she was Postgraduate Year 1 Resident, Sanford USD Medical Center. Edith A. Nutescu, Pharm.D., is Associate Professor, Department of Pharmacy Systems Outcomes and Policy, and Co-Director, Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago College of Pharmacy, Chicago. Paul A. Thompson, Ph.D., is Director, Methodology and Data Analysis Center, and Professor, Department of Pediatrics, Sanford School of Medicine, Sanford Research, Sioux Falls. Henry I. Bussey, Pharm.D., is President and Senior Editor, ClotCare.org, San Antonio, TX, and President, Genesis Clinical Research, San Antonio. Michael P. Gulseth, Pharm.D., BCPS, FASHP, is Program Director for Anticoagulation Services, Sanford USD Medical Center, and Adjunct Assistant Professor, College of Pharmacy, South Dakota State University, Sioux Falls.
authors.forename: Edith A
authors.initials: EA
authors.lastname: Nutescu
authors.affiliation: Ashley L. Barta, Pharm.D., is Clinical Pharmacist, Sanford USD Medical Center, Sioux Falls, SD; when this project was conducted she was Postgraduate Year 1 Resident, Sanford USD Medical Center. Edith A. Nutescu, Pharm.D., is Associate Professor, Department of Pharmacy Systems Outcomes and Policy, and Co-Director, Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago College of Pharmacy, Chicago. Paul A. Thompson, Ph.D., is Director, Methodology and Data Analysis Center, and Professor, Department of Pediatrics, Sanford School of Medicine, Sanford Research, Sioux Falls. Henry I. Bussey, Pharm.D., is President and Senior Editor, ClotCare.org, San Antonio, TX, and President, Genesis Clinical Research, San Antonio. Michael P. Gulseth, Pharm.D., BCPS, FASHP, is Program Director for Anticoagulation Services, Sanford USD Medical Center, and Adjunct Assistant Professor, College of Pharmacy, South Dakota State University, Sioux Falls.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Thompson
authors.affiliation: Ashley L. Barta, Pharm.D., is Clinical Pharmacist, Sanford USD Medical Center, Sioux Falls, SD; when this project was conducted she was Postgraduate Year 1 Resident, Sanford USD Medical Center. Edith A. Nutescu, Pharm.D., is Associate Professor, Department of Pharmacy Systems Outcomes and Policy, and Co-Director, Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago College of Pharmacy, Chicago. Paul A. Thompson, Ph.D., is Director, Methodology and Data Analysis Center, and Professor, Department of Pediatrics, Sanford School of Medicine, Sanford Research, Sioux Falls. Henry I. Bussey, Pharm.D., is President and Senior Editor, ClotCare.org, San Antonio, TX, and President, Genesis Clinical Research, San Antonio. Michael P. Gulseth, Pharm.D., BCPS, FASHP, is Program Director for Anticoagulation Services, Sanford USD Medical Center, and Adjunct Assistant Professor, College of Pharmacy, South Dakota State University, Sioux Falls.
authors.forename: Henry I
authors.initials: HI
authors.lastname: Bussey
authors.affiliation: Ashley L. Barta, Pharm.D., is Clinical Pharmacist, Sanford USD Medical Center, Sioux Falls, SD; when this project was conducted she was Postgraduate Year 1 Resident, Sanford USD Medical Center. Edith A. Nutescu, Pharm.D., is Associate Professor, Department of Pharmacy Systems Outcomes and Policy, and Co-Director, Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago College of Pharmacy, Chicago. Paul A. Thompson, Ph.D., is Director, Methodology and Data Analysis Center, and Professor, Department of Pediatrics, Sanford School of Medicine, Sanford Research, Sioux Falls. Henry I. Bussey, Pharm.D., is President and Senior Editor, ClotCare.org, San Antonio, TX, and President, Genesis Clinical Research, San Antonio. Michael P. Gulseth, Pharm.D., BCPS, FASHP, is Program Director for Anticoagulation Services, Sanford USD Medical Center, and Adjunct Assistant Professor, College of Pharmacy, South Dakota State University, Sioux Falls. michael.gulseth@sanfordhealth.org.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Gulseth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000175:diagnosis*; D006801:Humans; D019934:International Normalized Ratio / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013927:Thrombosis / Q000175:diagnosis* / Q000188:drug therapy*; D013997:Time Factors; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin