Abstract Concomitant use of Vitamin K antagonists (VKA) and statins is frequent in cardiovascular patients. However, clinical guidelines on this drug combination are divergent. Therefore, we performed a systematic review according to the PRISMA guidelines to evaluate the effect of statin initiation on coagulation among VKA users. Applying two broad search strategies for the drug interaction between VKA and statins in both Embase and Pubmed, 8,623 unique hits were obtained. In the final sample eight studies were included. The most frequent used VKA in the studies was warfarin while simvastatin was the most commonly initiated statin. All included studies showed a minor increase in the anticoagulant effect of VKA following statin initiation during VKA treatment. The reported increases in mean INR ranged from 0.15-0.65. The effect is likely to be of limited clinical relevance but should be evaluated individually.

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.