title: Prostate cancer risk among users of digoxin and other antiarrhythmic drugs in the Finnish Prostate Cancer Screening Trial.
abstract: OBJECTIVE
  Long-term usage of the antiarrhythmic drug digoxin has been connected to lowered risk of prostate cancer. A recent study has suggested that beta-blockers might also have similar risk-decreasing effects. We evaluated the association between use of digoxin, beta-blocker sotalol, and other antiarrhythmic drugs and prostate cancer risk in a retrospective cohort study.
  
  
  METHODS
  Our study population consisted of men in the Finnish Prostate Cancer Screening Trial during 1996-2012 (n = 78,615). During median follow-up of 12 years, 6,639 prostate cancer cases were diagnosed. The national prescription database was the source of the information of antiarrhythmic drug purchases. Data were analyzed using Cox regression method with medication use as a time-dependent variable.
  
  
  RESULTS
  No association was found for overall prostate cancer risk with antiarrhythmic drug use (HR 1.05 95% CI 0.94-1.18). Neither sotalol (HR 0.97 95% CI 0.76-1.24) nor digoxin (HR 1.01 95% CI 0.87-1.16) users had a decreased risk of prostate cancer. Similar results were obtained for high-grade (Gleason 7-10) and metastatic prostate cancer. Nevertheless, the risk estimates for Gleason 7-10 prostate cancer tended to decrease by duration of digoxin use (p for trend = 0.052), suggesting that the drug may reduce the risk in long-term usage (HR 0.71, 95% CI 0.49-1.03). In analysis stratified by screening trial arm, the protective association against Gleason 7-10 disease was observed only in the screening arm (HR 0.31, 95% CI 0.12-0.84 for men who had used digoxin for 5 years or longer).
  
  
  CONCLUSIONS
  Digoxin or other antiarrhythmic drugs are not associated with any clear decrease in prostate cancer risk. However, digoxin might have a benefit in long-term use by reducing risk of high-grade disease. Further research will be needed to evaluate possible effects on prostate cancer survival.
authors.affiliation: School of Medicine, University of Tampere, Medisiinarinkatu 3, 33014, Tampere, Finland. kaapu.kalle.j@student.uta.fi.
authors.forename: K J
authors.initials: KJ
authors.lastname: Kaapu
authors.affiliation: School of Medicine, University of Tampere, Medisiinarinkatu 3, 33014, Tampere, Finland.|Department of Urology, Tampere University Hospital, Tampere, Finland.
authors.forename: T J
authors.initials: TJ
authors.lastname: Murtola
authors.affiliation: Finnish Cancer Registry, Helsinki, Finland.
authors.forename: L
authors.initials: L
authors.lastname: Määttänen
authors.affiliation: Finnish Cancer Registry, Helsinki, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Talala
authors.affiliation: Department of Urology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Taari
authors.affiliation: School of Medicine, University of Tampere, Medisiinarinkatu 3, 33014, Tampere, Finland.|Department of Urology, Tampere University Hospital, Tampere, Finland.
authors.forename: T L J
authors.initials: TL
authors.lastname: Tammela
authors.affiliation: School of Health Sciences, University of Tampere, Tampere, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Auvinen
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004077:Digoxin / Q000627:therapeutic use*; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000473:pathology; D065840:Protective Factors; D012189:Retrospective Studies; D013015:Sotalol / Q000627:therapeutic use*
chemical_list: D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D004077:Digoxin; D013015:Sotalol; D017430:Prostate-Specific Antigen
keywords: Antiarrhythmic drugs; Cohort; Digoxin; Prostate cancer; Risk