Statin use decreases coagulation in users of vitamin K antagonists

Eur J Clin Pharmacol. 2016 Dec;72(12):1441-1447. doi: 10.1007/s00228-016-2138-6. Epub 2016 Oct 5.

Abstract

Purpose: 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.

Keywords: Coumarins; Drug interactions; Hydroxymethylglutaryl-CoA reductase inhibitors; Pharmacokinetics; Pharmacology.

Publication types

  • Clinical Trial

MeSH terms

  • Acenocoumarol / pharmacology*
  • Acenocoumarol / therapeutic use
  • Aged
  • Aged, 80 and over
  • Anticoagulants / pharmacology*
  • Anticoagulants / therapeutic use
  • Blood Coagulation / drug effects*
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • International Normalized Ratio
  • Male
  • Middle Aged
  • Phenprocoumon / pharmacology*
  • Phenprocoumon / therapeutic use
  • Vitamin K / antagonists & inhibitors*

Substances

  • Anticoagulants
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Vitamin K
  • Acenocoumarol
  • Phenprocoumon