title: Comparison of the Risk of Gastrointestinal Bleeding among Different Statin Exposures with Concomitant Administration of Warfarin: Electronic Health Record-Based Retrospective Cohort Study.
abstract: OBJECTIVE
  Patients who should be treated with both warfarin and a statin are frequently seen in vascular clinics. The risk for bleeding and potential drug interactions should be considered when prescribing both medications together. This study aimed to compare the risk for gastrointestinal bleeding among different statin exposures with concomitant administration of warfarin.
  
  
  METHODS
  This is a single-hospital retrospective cohort study. We included patients who were concomitantly exposed to one of four statins (pravastatin, simvastatin, atorvastatin, and rosuvastatin) and warfarin for up to 2 years (730 days). The observation period ended when a gastrointestinal bleeding event occurred or the observation was censored. Within-class comparisons were used, and 1:1 matching using a propensity score was performed for comparisons between each statin and all of the other statins. Kaplan-Meier analyses with log-rank tests and Cox proportional hazard regression analyses were conducted to determine associations with the risk of gastrointestinal bleeding.
  
  
  RESULTS
  Data were analyzed for 1,686 patients who were concomitantly administered a statin and warfarin. Log-rank tests for the gastrointestinal bleeding-free survival rate showed that the risk for gastrointestinal bleeding was significantly lower in the pravastatin group (p = 0.0499) and higher in the rosuvastatin group (p = 0.009). In the Cox proportional hazard regression analysis, the hazard ratio of 5.394 for gastrointestinal bleeding based on statin exposure in the rosuvastatin group was significant (95% confidence interval, 1.168-24.916).
  
  
  CONCLUSIONS
  There was a relatively high risk of gastrointestinal bleeding with rosuvastatin when administered concomitantly with warfarin.
authors.affiliation: Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Gyeonggi-do, Republic of Korea.
authors.forename: Dahye
authors.initials: D
authors.lastname: Shin
authors.affiliation: Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Gyeonggi-do, Republic of Korea.
authors.forename: Dukyong
authors.initials: D
authors.lastname: Yoon
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Gyeonggi-do, Republic of Korea.
authors.forename: Sun Gyo
authors.initials: SG
authors.lastname: Lim
authors.affiliation: Department of Neurology, Ajou University School of Medicine, Suwon, Gyeonggi-do, Republic of Korea.
authors.forename: Ji Man
authors.initials: JM
authors.lastname: Hong
authors.affiliation: Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Gyeonggi-do, Republic of Korea.|Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Gyeonggi-do, Republic of Korea.
authors.forename: Rae Woong
authors.initials: RW
authors.lastname: Park
authors.affiliation: Department of Neurology, Ajou University School of Medicine, Suwon, Gyeonggi-do, Republic of Korea.
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage; D000069059:Atorvastatin / Q000008:administration & dosage; D001281:Atrial Fibrillation / Q000188:drug therapy; D004347:Drug Interactions; D057286:Electronic Health Records; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000008:administration & dosage; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage; D019821:Simvastatin / Q000008:administration & dosage; D012984:Software; D062606:Tertiary Care Centers; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014859:Warfarin; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D019821:Simvastatin; D017035:Pravastatin