title: Placebo adherence, clinical outcomes, and mortality in the women's health initiative randomized hormone therapy trials.
abstract: BACKGROUND
  Medication adherence may be a proxy for healthy behaviors and other factors that affect outcomes. Prior studies of the association between placebo adherence and health outcomes have been limited primarily to men enrolled in clinical trials and cardiovascular disease outcomes. We examined associations between adherence to placebo and the risk of fracture, coronary heart disease, cancer, and all-cause mortality in the 2 Women's Health Initiative hormone therapy randomized trials.
  
  
  METHODS
  Postmenopausal women randomized to placebo with adherence measured at least once were eligible for analysis. Time-varying adherence was assessed by dispensing history and pill counts. Outcome adjudication was based on physician review of medical records. Cox proportional hazards models evaluated the relation between high adherence (≥80%) to placebo and various outcomes, referent to low adherence (<80%).
  
  
  RESULTS
  A total of 13,444 postmenopausal women were under observation for 106,066 person-years. High placebo adherence was inversely associated with most outcomes including hip fracture [hazard ratio (HR), 0.50; 95% confidence interval (CI), 0.33-0.78], myocardial infarction (HR, 0.69; 95% CI, 0.50-0.95), cancer death (HR, 0.60; 95% CI, 0.43-0.82), and all-cause mortality (HR, 0.64; 95% CI, 0.51-0.80) after adjustment for potential confounders. Women with low adherence to placebo were 20% more likely to have low adherence to statins and osteoporosis medications.
  
  
  CONCLUSIONS
  In the Women's Health Initiative clinical trials, high adherence to placebo was associated with favorable clinical outcomes and mortality. Until the healthy behaviors and/or other factors for which high adherence is a proxy can be better elucidated, caution is warranted when interpreting the magnitude of benefit of medication adherence.
authors.affiliation: Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 1530 3rd Ave South, FOT 805D, Birmingham, AL 35294, USA. jcurtis@uab.edu
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Larson
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Delzell
authors.forename: Maurice Alan
authors.initials: MA
authors.lastname: Brookhart
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Cadarette
authors.forename: Rowan
authors.initials: R
authors.lastname: Chlebowski
authors.forename: Suzanne
authors.initials: S
authors.lastname: Judd
authors.forename: Monika
authors.initials: M
authors.lastname: Safford
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Solomon
authors.forename: Andrea Z
authors.initials: AZ
authors.lastname: Lacroix
mesh_terms: D002423:Cause of Death; D015914:Estrogen Replacement Therapy / Q000706:statistics & numerical data; D005260:Female; D006620:Hip Fractures / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D008875:Middle Aged; D009026:Mortality; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D009369:Neoplasms / Q000453:epidemiology / Q000517:prevention & control; D015990:Placebo Effect; D010919:Placebos; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D016903:Drug Monitoring
chemical_list: D010919:Placebos