Introduction
The vitamin K antagonist warfarin
is used in the treatment and prevention of thromboembolic
events.1–3 Due to its narrow therapeutic index, use
of warfarin requires close monitoring of the international normalised
ratio (INR). Warfarin is metabolized by the cytochrome P450 (CYP) liver
enzymes, especially CYP2C9,4 which makes it highly
susceptible to drug-drug interactions (DDIs).1,4
Due to several overlaps in indications of use, coadministration of
warfarin and statins is common.5,6 A limited number of
generally conflicting studies have reported both that statin initiation
leads to moderate INR increases,7–10 as well as,
small INR changes of limited clinical relevance.11,12Despite limited evidence of a clinically relevant interaction between
warfarin and statins, commonly used online DDI guidelines consistently
advise clinicians to increase the frequency of INR monitoring and if
necessary adjust the warfarin dose, when initiating statin
treatment.13–15 This results in additional
consultations and blood testing, burdening both the patient and the
health care system.
To provide additional data on this potential DDI between statins and
warfarin, we conducted a large register-based study and examined the INR
changes in warfarin users following exposure to simvastatin,
atorvastatin, and rosuvastatin.