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Drug-drug interaction between warfarin and statins: A Danish cohort study
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  • Anna Engell,
  • Andreas Svendsen,
  • Bent Struer Lind,
  • Christen Andersen,
  • John Andersen,
  • Tora Willadsen,
  • Frederik Persson,
  • Anton Pottegard
Anna Engell
Hvidovre Hospital
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Andreas Svendsen
Odense Universitetshospital
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Bent Struer Lind
Hvidovre Hospital
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Christen Andersen
Copenhagen University Research Unit for General Practice
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John Andersen
Copenhagen University Research Unit for General Practice
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Tora Willadsen
Copenhagen University Research Unit for General Practice
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Frederik Persson
Steno Diabetes Center Copenhagen
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Anton Pottegard
University of Southern Denmark
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Peer review status:ACCEPTED

15 Apr 2020Submitted to British Journal of Clinical Pharmacology
16 Apr 2020Submission Checks Completed
16 Apr 2020Assigned to Editor
17 Apr 2020Reviewer(s) Assigned
11 May 2020Review(s) Completed, Editorial Evaluation Pending
15 May 2020Editorial Decision: Revise Major
26 May 20201st Revision Received
27 May 2020Submission Checks Completed
27 May 2020Assigned to Editor
27 May 2020Review(s) Completed, Editorial Evaluation Pending
03 Jun 2020Editorial Decision: Accept

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=1,363), 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.