Assessing the Risks Associated with Warfarin Therapy and Related Methodological Considerations

Résumé du livre

Warfarin is an anticoagulant medication that is used for the prevention and treatment of venous and arterial thrombotic complications. The evaluation of the risks associated with warfarin therapy, and its interaction with other drugs, poses important methodological challenges. In this thesis, we studied two of these risks and assessed techniques to address these methodological challenges using data from the United Kingdom's General Practice Research Database (GPRD). First, we conducted a case-control study to examine the risk of gastrointestinal bleeding associated with warfarin use. We identified 4028 cases and 40171 matched controls from 2000 through 2005. Using conditional logistic regression, we found an increased risk of bleeding associated with warfarin use [adjusted odds ratio (OR) 2.15; 95% confidence interval (CI):1.81 to 2.54]. We also observed an increased risk due to drug-drug interactions between warfarin and other anti-thrombotic drugs. We also observed evidence of channelling bias as warfarin users were less likely to be prescribed other anti-thrombotic drugs. Second, as warfarin has many weak interactions, we re-analyzed our case-control study using a marginal structural model to assess the overall impact of effect modification. This analysis produced a different estimate (for the population level instead of the individual level) for the risk of bleeding associated with warfarin [OR 17.2; 95% CI: 6.5 to 37.7] than analysis with conditional logistic regression. The impact of effect modification on these estimates was then assessed with a Monte Carlo simulation study. Third, we created a cohort of patients given their first prescription of warfarin, ibuprofen, statins, or rofecoxib/celecoxib from 2001 through 2003.