title: Statin use decreases coagulation in users of vitamin K antagonists.
abstract: OBJECTIVE
  The purpose of the study is to determine the immediate and long-term effect of statins on coagulation in patients treated with vitamin K antagonists (VKAs).
  
  
  METHODS
  We selected patients on VKAs of two Dutch anticoagulation clinics who initiated treatment with a statin between 2009 and 2013. Patients who initiated or stopped concomitant drugs that interact with VKAs or were hospitalised during follow-up were excluded. The VKA dosage (mg/day) after statin initiation was compared with the last VKA dosage before the statin was started. Immediate and long-term differences in VKA dosage (at 6 and 12 weeks) were calculated with a paired student t test.
  
  
  RESULTS
  Four hundred thirty-five phenprocoumon users (mean age 70 years, 60 % men) and 303 acenocoumarol users (mean age 69 years, 58 % men) were included. After start of statin use, the immediate phenprocoumon dosage was 0.02 mg/day (95 % CI, 0.00 to 0.03) lower. At 6 and 12 weeks, these phenprocoumon dosages were 0.03 (95 % CI, 0.01 to 0.05) and 0.07 mg/day (95 % CI, 0.04 to 0.09) lower as compared with the dosage before first statin use. In acenocoumarol users, VKA dosage was 0.04 mg/day (95%CI, 0.01 to 0.07) (immediate effect), 0.10 (95 % CI, 0.03 to 0.16) (at 6 weeks), and 0.11 mg/day (95 % CI, 0.04 to 0.18) (after 12 weeks) lower.
  
  
  CONCLUSIONS
  Initiation of statin treatment was associated with an immediate and long-term minor although statistically significant decrease in VKA dosage in both phenprocoumon and acenocoumarol users, which suggests that statins may have anticoagulant properties.
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands. n.van_rein@lumc.nl.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands. n.van_rein@lumc.nl.
authors.forename: Nienke
authors.initials: N
authors.lastname: van Rein
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.|Star-Medical Diagnostic Center, Rotterdam, The Netherlands.
authors.forename: J S
authors.initials: JS
authors.lastname: Biedermann
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: S M
authors.initials: SM
authors.lastname: Bonafacio
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.|Star-Medical Diagnostic Center, Rotterdam, The Netherlands.
authors.forename: M J H A
authors.initials: MJ
authors.lastname: Kruip
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: F J M
authors.initials: FJ
authors.lastname: van der Meer
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.|Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: W M
authors.initials: WM
authors.lastname: Lijfering
mesh_terms: D000074:Acenocoumarol / Q000494:pharmacology* / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000494:pharmacology* / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010644:Phenprocoumon / Q000494:pharmacology* / Q000627:therapeutic use; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014812:Vitamin K; D000074:Acenocoumarol; D010644:Phenprocoumon
keywords: Coumarins; Drug interactions; Hydroxymethylglutaryl-CoA reductase inhibitors; Pharmacokinetics; Pharmacology