Drug-drug interaction between warfarin and statins: A Danish cohort study

Br J Clin Pharmacol. 2021 Feb;87(2):694-699. doi: 10.1111/bcp.14428. Epub 2020 Jun 30.

Abstract

Initiation of statin treatment is suggested to increase the international normalised ratio (INR) among warfarin users. However, available data is limited and conflicting. We conducted a register-based cohort study to evaluate the drug-drug interaction between warfarin and statins. By linking data on INR measurements and filled prescriptions, we identified warfarin users 2000-2015 initiating simvastatin (n = 1363), atorvastatin (n = 165) or rosuvastatin (n = 23). Simvastatin initiation led to an increase in mean INR from 2.40 to 2.71, with INRs peaking after 4 weeks, corresponding to a mean change of 0.32 (95%CI 0.25-0.38). High-dose and low-dose simvastatin led to comparable changes (mean change 0.33 vs 0.29). Initiation of atorvastatin and rosuvastatin lead to INR increases of 0.27 (95%CI 0.12-0.42) and 0.30 (95%CI -0.09-0.69). In conclusion, initiation of simvastatin, atorvastatin or rosuvastatin among warfarin users led to a minor increase in INR. The magnitude of this change is for most patients likely of limited clinical relevance.

Keywords: anticoagulants and warfarin; drug interactions; statins.

MeSH terms

  • Anticoagulants
  • Cohort Studies
  • Denmark / epidemiology
  • Drug Interactions
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • International Normalized Ratio
  • Pharmaceutical Preparations*
  • Warfarin / adverse effects

Substances

  • Anticoagulants
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pharmaceutical Preparations
  • Warfarin