title: Association between use of warfarin with common sulfonylureas and serious hypoglycemic events: retrospective cohort analysis.
abstract: OBJECTIVE
  Is warfarin use associated with an increased risk of serious hypoglycemic events among older people treated with the sulfonylureas glipizide and glimepiride?
  
  
  METHODS
  This was a retrospective cohort analysis of pharmacy and medical claims from a 20% random sample of Medicare fee for service beneficiaries aged 65 years or older. It included 465,918 beneficiaries with diabetes who filled a prescription for glipizide or glimepiride between 2006 and 2011 (4,355,418 person quarters); 71,895 (15.4%) patients also filled a prescription for warfarin (416,479 person quarters with warfarin use). The main outcome measure was emergency department visit or hospital admission with a primary diagnosis of hypoglycemia in person quarters with concurrent fills of warfarin and glipizide/glimepiride compared with the rates in quarters with glipizide/glimepiride fills only, Multivariable logistic regression was used to adjust for individual characteristics. Secondary outcomes included fall related fracture and altered consciousness/mental status.
  
  
  CONCLUSIONS
  In quarters with glipizide/glimepiride use, hospital admissions or emergency department visits for hypoglycemia were more common in person quarters with concurrent warfarin use compared with quarters without warfarin use (294/416,479 v 1903/3,938,939; adjusted odds ratio 1.22, 95% confidence interval 1.05 to 1.42). The risk of hypoglycemia associated with concurrent use was higher among people using warfarin for the first time, as well as in those aged 65-74 years. Concurrent use of warfarin and glipizide/glimepiride was also associated with hospital admission or emergency department visit for fall related fractures (3919/416,479 v 20,759/3,938,939; adjusted odds ratio 1.47, 1.41 to 1.54) and altered consciousness/mental status (2490/416,479 v 14,414/3,938,939; adjusted odds ratio 1.22, 1.16 to 1.29). Unmeasured factors could be correlated with both warfarin use and serious hypoglycemic events, leading to confounding. The findings may not generalize beyond the elderly Medicare population.
  
  
  CONCLUSIONS
  A substantial positive association was seen between use of warfarin with glipizide/glimepiride and hospital admission/emergency department visits for hypoglycemia and related diagnoses, particularly in patients starting warfarin. The findings suggest the possibility of a significant drug interaction between these medications.
  
  
  BACKGROUND
  JAR and DPG receive support from the National Institute on Aging, the Commonwealth Fund, and the Leonard D. Schaeffer Center for Health Policy and Economics at the University of Southern California. ABJ receives support from the NIH Office of the Director. No additional data are available.
authors.affiliation: Leonard D. Schaeffer Center for Health Policy and Economics Price School of Public Policy, University of Southern California, 635 Downey Way, Los Angeles, CA 90089-3333, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Romley
authors.affiliation: School of Pharmacy, University of Southern California, 635 Downey Way, Los Angeles, CA 90089-3333, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Gong
authors.affiliation: Department of Health Care Policy, Harvard Medical School, 180 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Anupam B
authors.initials: AB
authors.lastname: Jena
authors.affiliation: Leonard D. Schaeffer Center for Health Policy and Economics Price School of Public Policy, School of Pharmacy, and Dornsife College of Letters, Arts and Sciences, University of Southern California, 635 Downey Way, Los Angeles, CA 90089-3333, USA Department of Health Care Policy, Harvard Medical School, 180 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Dana P
authors.initials: DP
authors.lastname: Goldman
authors.affiliation: School of Pharmacy, University of Southern California, Health Sciences Campus, Los Angeles, CA 90089-9121, USA.
authors.forename: Bradley
authors.initials: B
authors.lastname: Williams
authors.affiliation: Keck School of Medicine, University of Southern California, 150 N. Robertson Blvd, Suite 210, Beverly Hills, CA 90211, USA momofmax@mac.com.
authors.forename: Anne
authors.initials: A
authors.lastname: Peters
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D004636:Emergency Service, Hospital; D005260:Female; D005913:Glipizide / Q000627:therapeutic use*; D006760:Hospitalization; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D006278:Medicare; D012189:Retrospective Studies; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D014481:United States / Q000453:epidemiology; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D014859:Warfarin; C057619:glimepiride; D005913:Glipizide