The American Journal of Medicine
Volume 123, Issue 2 , Pages 151-157 , February 2010

Fibrate/Statin Initiation in Warfarin Users and Gastrointestinal Bleeding Risk

  • Hedi Schelleman, PhD

      Affiliations

    • Center for Clinical Epidemiology and Biostatistics and Center for Education and Research on Therapeutics, University of Pennsylvania School of Medicine, Philadelphia
    • Corresponding Author InformationRequests 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
    • ,
  • Warren B. Bilker, PhD

      Affiliations

    • Center for Clinical Epidemiology and Biostatistics and Center for Education and Research on Therapeutics, University of Pennsylvania School of Medicine, Philadelphia
    • ,
  • Colleen M. Brensinger, MS

      Affiliations

    • Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia
    • ,
  • Fei Wan, MS

      Affiliations

    • Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia
    • ,
  • Yu-Xiao Yang, MD, MSCE

      Affiliations

    • Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia
    • Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia
    • ,
  • Sean Hennessy, PharmD, PhD

      Affiliations

    • Center for Clinical Epidemiology and Biostatistics and Center for Education and Research on Therapeutics, University of Pennsylvania School of Medicine, Philadelphia

References 

  1. Wysowski DK, Nourjah P, Swartz L. Bleeding complications with warfarin use: a prevalent adverse effect resulting in regulatory action. Arch Intern Med. 2007;167:1414–1419
  2. Holbrook AM, Pereira JA, Labiris R, et al. Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005;165:1095–1106
  3. Douketis JD, Arneklev K, Goldhaber SZ, et al. Comparison of bleeding in patients with nonvalvular atrial fibrillation treated with ximelagatran or warfarin: assessment of incidence, case-fatality rate, time course and sites of bleeding, and risk factors for bleeding. Arch Intern Med. 2006;166:853–859
  4. Sakaeda T, Fujino H, Komoto C, et al. Effects of acid and lactone forms of eight HMG-CoA reductase inhibitors on CYP-mediated metabolism and MDR1-mediated transport. Pharm Res. 2006;23:506–512
  5. Wittkowsky AK, Boccuzzi SJ, Wogen J, et al. Frequency of concurrent use of warfarin with potentially interacting drugs. Pharmacotherapy. 2004;24:1668–1674
  6. Hickmott H, Wynne H, Kamali F. The effect of simvastatin co-medication on warfarin anticoagulation response and dose requirements. Thromb Haemost. 2003;89:949–950
  7. MICROMEDEX. www.thomsonhc.com/hcs/librarianAccessed August 10, 2007
  8. Wolters Kluwer Health. Drug Facts & Comparisons 4.0. http://www.factsandcomparisons.comAccessed July 7, 2007
  9. Miller DB, Spence JD. Clinical pharmacokinetics of fibric acid derivatives (fibrates). Clin Pharmacokinet. 1998;34:155–162
  10. Stern R, Abel R, Gibson GL, Besserer J. Atorvastatin does not alter the anticoagulant activity of warfarin. J Clin Pharmacol. 1997;37:1062–1064
  11. Haber LT, Maier A, Gentry PR, et al. Genetic polymorphisms in assessing interindividual variability in delivered dose. Regul Toxicol Pharmacol. 2002;35(2 Pt 1):177–197
  12. Ahmad S. Gemfibrozil interaction with warfarin sodium (coumadin). Chest. 1990;98:1041–1042
  13. Trilli LE, Kelley CL, Aspinall SL, Kroner BA. Potential interaction between warfarin and fluvastatin. Ann Pharmacother. 1996;30:1399–1402
  14. Kline SS, Harrell CC. Potential warfarin-fluvastatin interaction. Ann Pharmacother. 1997;31:790
  15. Rindone JP, Keng HC. Gemfibrozil-warfarin drug interaction resulting in profound hypoprothrombinemia. Chest. 1998;114:641–642
  16. Andrus MR. Oral anticoagulant drug interactions with statins: case report of fluvastatin and review of the literature. Pharmacotherapy. 2004;24:285–290
  17. Mann D, Reynolds K, Smith D, Muntner P. Trends in statin use and low-density lipoprotein cholesterol levels among US adults: impact of the 2001 National Cholesterol Education Program guidelines. Ann Pharmacother. 2008;42:1208–1215
  18. Hennessy S, Carson JL, Ray WA, Strom BL. Medicaid databases. In:  Strom BL editors. Pharmacoepidemiology. 4th edn.. Chichester, UK: John Wiley and Sons, Inc; 2005;p. 281–294
  19. MedPac: Medicare Payment Advisory Commission. Report to the Congress: New Approaches in Medicare. Washington, DC: Medicare Payment Advisory Commission; 2004;
  20. Hennessy S, Leonard CE, Palumbo CM, et al. Quality of Medicaid and Medicare data obtained through Centers for Medicare and Medicaid Services (CMS). Med Care. 2007;45:1216–1220
  21. Witt DM, Sadler MA, Shanahan RL, et al. Effect of a centralized clinical pharmacy anticoagulation service on the outcomes of anticoagulation therapy. Chest. 2005;127:1515–1522
  22. West SL, Strom BL, Poole C. Validity of pharmacoepidemiologic drug and diagnosis data. In:  Strom BL editors. Pharmacoepidemiology. 4th edn.. Chichester, UK: John Wiley and Sons, Inc; 2005;p. 709–766
  23. Flanders WD, Louv WC. The exposure odds ratio in nested case-control studies with competing risks. Am J Epidemiol. 1986;124:684–692
  24. Tournier M, Moride Y, Lesk M, et al. The depletion of susceptibles effect in the assessment of burden-of-illness: the example of age-related macular degeneration in the community-dwelling elderly population of Quebec. Can J Clin Pharmacol. 2008;15:e22–e35
  25. Mickey RM, Greenland S. The impact of confounder selection criteria on effect estimation. Am J Epidemiol. 1989;129:125–137
  26. Jacobson TA. Comparative pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin when coadministered with cytochrome P450 inhibitors. Am J Cardiol. 2004;94:1140–1146
  27. Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006;80:565–581

 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.

PII: S0002-9343(09)00862-6

doi: 10.1016/j.amjmed.2009.07.020

The American Journal of Medicine
Volume 123, Issue 2 , Pages 151-157 , February 2010

Article Tools

* Image Usage & Resolution