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.