Fibrate/Statin initiation in warfarin users and gastrointestinal bleeding risk.
OBJECTIVE
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 > or =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.
Schelleman
Hedi
H
Center for Clinical Epidemiology and Biostatistics and Center for Education and Research on Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, USA. hschelle@mail.med.upenn.edu
Bilker
Warren B
WB
Brensinger
Colleen M
CM
Wan
Fei
F
Yang
Yu-Xiao
YX
Hennessy
Sean
S
D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000925:Anticoagulants / Q000627:therapeutic use*; D016022:Case-Control Studies; D002995:Clofibric Acid / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000453:epidemiology*; D006760:Hospitalization; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014481:United States; D014859:Warfarin / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D000925:Anticoagulants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002995:Clofibric Acid; D014859:Warfarin