title: Drospirenone-containing oral contraceptive pills and the risk of venous thromboembolism: a systematic review of observational studies.
abstract: BACKGROUND
  The effects of fourth-generation drospirenone-containing combined oral contraceptives (COCs) on the risk of venous thromboembolism (VTE) are controversial.
  
  
  OBJECTIVE
  To assess the methodological strengths and limitations of the evidence on the VTE risk of these COCs.
  
  
  METHODS
  We searched CINAHL, the Cochrane Library, EMBASE, HealthStar, Medline, and the Science Citation Index.
  
  
  METHODS
  Studies were included if they were cohort and case-control studies, reported a venous thrombotic outcome, had a comparator group, reported an effect measure of the association of interest, and were published in English or French.
  
  
  METHODS
  We assessed study quality using the ROBINS-I tool and assessed the presence of four common sources of bias: prevalent user bias, inappropriate choice of comparator, VTE misclassification, and confounding.
  
  
  RESULTS
  Our systematic review included 17 studies. The relative risks of VTE associated with drospirenone- versus second-generation levonorgestrel-containing COCs ranged from 1.0 to 3.3. Based on ROBINS-I, three studies had a moderate risk, ten had a serious risk, and four had a critical risk. Nine studies included prevalent users, four included inappropriate comparators, four had VTE misclassification, and five did not account for two or more important confounding factors. The three highest quality studies had relative risks ranging from 1.0 to 1.57.
  
  
  CONCLUSIONS
  As a result of the methodological limitations of the individual studies, the VTE risk of drospirenone-containing COCs remains unknown. The highest quality studies suggest there are no or slightly increased harmful effects, but their confidence limits do not rule out an almost doubling of the risk.
  
  
  CONCLUSIONS
  Systematic review of drospirenone: best studies show no or slightly increased VTE risk (versus levonorgestrel).
authors.affiliation: Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada.|Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Larivée
authors.affiliation: Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada.|Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.|Department of Medicine, McGill University, McGill University, Montreal, QC, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Suissa
authors.affiliation: Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada.|Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Khosrow-Khavar
authors.affiliation: Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada.|Division of General Internal Medicine, Jewish General Hospital, Montreal, QC, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Tagalakis
authors.affiliation: Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada.|Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.|Department of Medicine, McGill University, McGill University, Montreal, QC, Canada.
authors.forename: K B
authors.initials: KB
authors.lastname: Filion
mesh_terms: D000328:Adult; D000736:Androstenes / Q000009:adverse effects*; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects*; D005260:Female; D006801:Humans; D064887:Observational Studies as Topic; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000139:chemically induced*
chemical_list: D000736:Androstenes; D003277:Contraceptives, Oral, Combined; C035144:drospirenone
keywords: Drospirenone; drug safety; oral contraceptives; pharmacoepidemiology; venous thromboembolism