title: Association between Exposure to Benzodiazepines and Related Drugs and Survivorship of Total Hip Replacement in Arthritis: A Population-Based Cohort Study of 246,940 Patients.
abstract: Total hip replacement (THR) is successful in treating hip arthritis. Prosthetic survivorship may depend on the medications taken by the patient; particularly, the role of benzodiazepines and related drugs (Z-drugs) with THR revision has been poorly investigated. Our objective was to compare THR short-term survivorship according to level of exposure to benzodiazepine and Z-drugs.
  
  
  
  All French patients aged 40 years or older, having undergone primary THR from January 1, 2009, through December 31, 2012, for arthritis according to French national health insurance databases were included in the cohort. Outcome of interest was THR revision, including any surgical procedure in which the implant or any component was changed or removed. Follow-up started the day the primary THR was performed. Observations were right-censored on December 31, 2014, if neither revision nor death had yet occurred. Exposure of interest was the cumulative defined daily doses per day (cDDD/day) of benzodiazepines and Z-drugs dispensed within 6 months before or after inclusion. We defined four exposure groups; cDDD/d = 0: unexposed; <0.08: low exposure;] 0.08-0.38]: medium exposure; >0.38: high exposure. THR survivorship was assessed according to level of exposure to benzodiazepines and Z-drugs in univariate and multivariate Cox models adjusted for patient, THR and implanting center characteristics.
  
  
  
  The study cohort comprised 246,940 individuals: mean age at baseline, 69.9 years; women, 57.9%; unexposed: 51.7%; low exposure: 16.7%; medium exposure: 15.9%; and high exposure: 15.7%. During the median 45-month follow-up, 9043 individuals underwent prosthetic revision. Adjusted hazard ratios in low, medium and high exposed groups were 1.18 (95%CI, 1.12-1.26; P<0.001), 1.32 (95%CI, 1.24-1.40; P<0.001) and 1.37 (95%CI, 1.29-1.45; P<0.001), respectively, compared to unexposed.
  
  
  
  Exposure to benzodiazepines and Z-drugs is associated with an increased risk of THR revision, with a dose-response relationship. Cautious prescribing might be needed as well as careful history examination and assessment of risk for patients with a hip prosthesis.
authors.affiliation: Department of Epidemiology of Health Products, Division for Science and European Strategy, French National Agency for Medicines and Health Products Safety (ANSM), Saint-Denis, France.
authors.forename: Dan
authors.initials: D
authors.lastname: Beziz
authors.affiliation: Department of Epidemiology of Health Products, Division for Science and European Strategy, French National Agency for Medicines and Health Products Safety (ANSM), Saint-Denis, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Colas
authors.affiliation: Department of Epidemiology of Health Products, Division for Science and European Strategy, French National Agency for Medicines and Health Products Safety (ANSM), Saint-Denis, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Collin
authors.affiliation: Department of Epidemiology of Health Products, Division for Science and European Strategy, French National Agency for Medicines and Health Products Safety (ANSM), Saint-Denis, France.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Dray-Spira
authors.affiliation: Department of Epidemiology of Health Products, Division for Science and European Strategy, French National Agency for Medicines and Health Products Safety (ANSM), Saint-Denis, France.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Zureik
mesh_terms: D000328:Adult; D000368:Aged; D001168:Arthritis / Q000628:therapy*; D019644:Arthroplasty, Replacement, Hip / Q000295:instrumentation*; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011475:Prosthesis Failure / Q000187:drug effects*; D012086:Reoperation / Q000706:statistics & numerical data*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D001569:Benzodiazepines