title: Prevalence of Drug Combinations Increasing Bleeding Risk Among Warfarin Users With and Without Alzheimer's Disease.
abstract: OBJECTIVE
  The aim of this study was to analyse the prevalence and predictors of drug combinations increasing bleeding risk among warfarin users with and without Alzheimer's disease (AD).
  
  
  METHODS
  This retrospective observational study utilised data from the Finnish MEDALZ-2005 cohort. The MEDALZ-2005 study included all community-dwelling persons with a clinically verified diagnosis of AD at the end of 2005, and one comparison person without AD for each case. Data on drug use was collected from the Prescription Register. We included persons who were warfarin users during the study period 2006-2009. Drug combinations increasing bleeding risk with warfarin included selective serotonin reuptake inhibitors (SSRIs), non-steroidal anti-inflammatory agents (NSAIDs), other antithrombotic drugs and tramadol. Factors associated with combination use were investigated with logistic regression.
  
  
  RESULTS
  During the follow-up, 3385 persons with AD and 4830 persons without AD used warfarin. Drug combinations increasing bleeding risk were more common in warfarin users with AD than without AD [35.9 and 30.5%, respectively (p < 0.0001)]. The most common combination was SSRIs and warfarin, which was more common among persons with AD (23.8%) than among persons without AD (10.9%). NSAIDs and warfarin combination was more common among persons without AD. Combination use was associated with AD, female gender, younger age, diabetes mellitus, rheumatoid arthritis and asthma/chronic obstructive pulmonary disease (COPD).
  
  
  CONCLUSIONS
  Use of drug combinations increasing bleeding risk was more common among warfarin users with AD. Special attention should be paid to minimise the duration of concomitant use and to find safer alternatives without increased bleeding risk.
authors.affiliation: Kuopio Research Centre of Geriatric Care, University of Eastern Finland, PO Box 1627, 70211, Kuopio, Finland. heidi.taipale@uef.fi.|School of Pharmacy, University of Eastern Finland, Kuopio, Finland. heidi.taipale@uef.fi.|Research Centre for Comparative Effectiveness and Patient Safety (RECEPS), University of Eastern Finland, Kuopio, Finland. heidi.taipale@uef.fi.
authors.forename: Heidi
authors.initials: H
authors.lastname: Taipale
authors.affiliation: Kuopio Research Centre of Geriatric Care, University of Eastern Finland, PO Box 1627, 70211, Kuopio, Finland.|School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Vuorikari
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Tanskanen
authors.affiliation: Kuopio Research Centre of Geriatric Care, University of Eastern Finland, PO Box 1627, 70211, Kuopio, Finland.|School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Marjaana
authors.initials: M
authors.lastname: Koponen
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Tiihonen
authors.affiliation: School of Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Raimo
authors.initials: R
authors.lastname: Kettunen
authors.affiliation: Kuopio Research Centre of Geriatric Care, University of Eastern Finland, PO Box 1627, 70211, Kuopio, Finland.|School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Hartikainen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D016022:Case-Control Studies; D004359:Drug Therapy, Combination / Q000009:adverse effects*; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects; D005387:Finland / Q000453:epidemiology; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D014147:Tramadol / Q000008:administration & dosage / Q000009:adverse effects; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005343:Fibrinolytic Agents; D017367:Selective Serotonin Reuptake Inhibitors; D014147:Tramadol; D014859:Warfarin