Marine L Andersson1, Buster Mannheimer2,3, Jonatan D Lindh1. 1. Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska University Hospital Huddinge, Stockholm, Sweden. 2. Department of Clinical Science and Education at Södersjukhuset, Karolinska Institutet, Stockholm, Sweden. buster.mannheimer@sll.se. 3. Section of Diabetes and Endocrinology, Department of Internal Medicine, Södersjukhuset, Sjukhusbacken 8-10, 118 82, Stockholm, Sweden. buster.mannheimer@sll.se.
Abstract
PURPOSE: Some data indicate that simvastatin may increase the anticoagulative effect in patients treated with warfarin, but the evidence is scarce. The aim of the present study was to investigate how the anticoagulative effect of warfarin is affected by the initiation of simvastatin in a very large patient sample. METHODS: In a retrospective cohort study, we included 5637 individuals on warfarin treatment initiating simvastatin. INR values and warfarin doses were calculated week-by-week during co-treatment. Data were obtained from two large Swedish warfarin registers and from the Swedish Prescribed Drug Register. RESULTS: INR increased from 2.43 at baseline to 2.58, 4 weeks after simvastatin initiation, and did not stabilize until the last quarter of the year studied. Consequently, the proportion of patients with an INR above 3 increased from around 8 to 15%. CONCLUSIONS: In conclusion, initiation of simvastatin resulted in moderately increased INR values and subsequent dose decreases in patients already on warfarin. In order to avoid the increased risk of bleeding, the initiation of simvastatin may be accompanied by closer INR monitoring.
PURPOSE: Some data indicate that simvastatin may increase the anticoagulative effect in patients treated with warfarin, but the evidence is scarce. The aim of the present study was to investigate how the anticoagulative effect of warfarin is affected by the initiation of simvastatin in a very large patient sample. METHODS: In a retrospective cohort study, we included 5637 individuals on warfarin treatment initiating simvastatin. INR values and warfarin doses were calculated week-by-week during co-treatment. Data were obtained from two large Swedish warfarin registers and from the Swedish Prescribed Drug Register. RESULTS: INR increased from 2.43 at baseline to 2.58, 4 weeks after simvastatin initiation, and did not stabilize until the last quarter of the year studied. Consequently, the proportion of patients with an INR above 3 increased from around 8 to 15%. CONCLUSIONS: In conclusion, initiation of simvastatin resulted in moderately increased INR values and subsequent dose decreases in patients already on warfarin. In order to avoid the increased risk of bleeding, the initiation of simvastatin may be accompanied by closer INR monitoring.
Entities:
Keywords:
Cytochrome P-450 CYP2C9; Drug interactions; International normalized ratio; Simvastatin; Warfarin
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