Fibrate/Statin Initiation in Warfarin Users and Gastrointestinal Bleeding Risk
Abstract
Purpose
To evaluate whether initiation of a fibrate or statin increases the risk of hospitalization for gastrointestinal bleeding in warfarin users.
Methods
We used Medicaid claims data (1999-2003) to perform an observational case-control study nested within person-time exposed to warfarin in those ≥18 years (n=353,489). Gastrointestinal bleeding cases were matched to 50 controls based on index date and state.
Results
Chronic warfarin users had an increased odds ratio of gastrointestinal bleeding upon initiation of gemfibrozil (1.88; 95% confidence interval [CI], 1.00-3.54] for the first prescription; 1.75; 95% CI, 0.77-3.95 for the second prescription); simvastatin (1.46; 95% CI, 1.03-2.07 for the first prescription; 1.60; 95% CI, 1.07-2.39 for the second prescription); or atorvastatin (1.39; 95% CI, 1.07-1.81 for the first prescription; 1.05; 95% CI, 0.73-1.52 for the second prescription). In contrast, no increased risk was found with pravastatin initiation (0.75; 95% CI, 0.39-1.46 for the first prescription; 0.90; 95% CI, 0.43-1.91 for the second prescription).
Conclusions
Initiation of a fibrate or statin that inhibits CYP3A4 enzymes, including atorvastatin, was associated with an increased risk of hospitalization for gastrointestinal bleeding. Initiation of pravastatin, which is mainly excreted unchanged, was not associated with an increased risk.
aCenter for Clinical Epidemiology and Biostatistics and Center for Education and Research on Therapeutics, University of Pennsylvania School of Medicine, Philadelphia
bCenter for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia
cDivision of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia
Requests for reprints should be addressed to Hedi Schelleman, PhD, University of Pennsylvania School of Medicine, 826 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021
Funding: This project was funded by National Institute on Aging grant R01AG02152. Apart from suggestions from reviewers during the peer review process, the funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. Part of the infrastructure for this study was funded by the Clinical and Translational Science Award 5KL2RR024132.
Conflict of Interest: Dr. Schelleman has had travel to scientific conferences paid for by pharmacoepidemiology training funds contributed by pharmaceutical manufacturers. Dr. Bilker has consulted for Johnson & Johnson and Astra Zeneca, unrelated to warfarin, fibrates, and statins. Ms. Brensinger has consulted for a law firm representing Pfizer, unrelated to warfarin, fibrates, and statins. Dr. Yang has served as a consultant for AstraZeneca and has received grant support from AstraZeneca, Wyeth-Ayerst Laboratories, and GlaxoSmithKline, unrelated to warfarin, fibrates, and statins. Dr. Hennessy has had funding from Pfizer and consulted for a law firm representing Bayer and Pfizer, unrelated to warfarin, fibrates, and statins. Mr. Wan had no potential conflict of interest to declare.
Authorship: All authors had access to the data and a role in writing the manuscript.
ABSTRACT
