Effect of Hepatitis C Drugs on Blood Coagulability in Patients on Warfarin Using the Medical Information Database Network (MID-NET®) in Japan

Abstract

Background Previous studies suggested that direct-acting antivirals (DAAs) against hepatitis C increased the blood coagulability of patients on warfarin. This study aims to descriptively investigate the effects of DAAs on the blood coagulability and liver function of patients on warfarin in Japan. Methods The Medical Information Database Network (MID-NET®) was used as data source. Fluctuations of blood coagulability and liver function were examined before and after DAA treatment in patients who were prescribed both DAAs and warfarin at least once during the study period from January 1, 2010, to December 31, 2017. Results For the 16 eligible patients, the mean values of both PT-INR and WSI (warfarin sensitivity index) defined as the value obtained by dividing the PT-INR by the warfarin daily dose slightly decreased at the date of completion of the DAA treatment in comparison with those at the date of initiation and subsequently increased at 12 weeks after treatment completion. In contrast, the warfarin daily dose increased at the date of completion of the DAA treatment, followed by a decrease at 12 weeks after its completion. Several laboratory tests related to the liver function also revealed a similar decrease at the end of the DAA treatment. Conclusion The analysis of MID-NET® data provides useful information on drug safety assessment of real-world patients. The results of this study imply that fluctuation of the liver function test results may relate to the fluctuation of blood coagulability in patients on both DAA and warfarin. This study contributes to a deeper understanding of the usefulness and limitations of real-world data in MID-NET® for regulatory purposes.

Use of National Database of Health Insurance Claims and Specific Health Checkups for examining practical utilization and safety signal of a drug to support regulatory assessment on postmarketing drug safety in Japan

“…Therefore, we selected the NDB as a data source for these studies. MID-NET R is usually selected for a study in which laboratory test results are necessary for analysis (29)(30)(31)(32). As described above, an understanding of the characteristics of each database is important to select a data source fit to a study purpose.…”