Charles E Leonard1, Colleen M Brensinger2, Warren B Bilker3, Stephen E Kimmel4, Xu Han5, Young Hee Nam6, Joshua J Gagne7, Margaret J Mangaali8, Sean Hennessy9. 1. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: celeonar@mail.med.upenn.edu. 2. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: cbrensin@mail.med.upenn.edu. 3. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: warren@upenn.edu. 4. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Medicine, Division of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: stevek@mail.med.upenn.edu. 5. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: hanxu1@mail.med.upenn.edu. 6. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: ynam@mail.med.upenn.edu. 7. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: jgagne1@partners.org. 8. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: mmanga@mail.med.upenn.edu. 9. Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: hennessy@upenn.edu.
Abstract
BACKGROUND: Drug interactions, particularly those involving warfarin, are a major clinical and public health problem. Minimizing serious bleeding caused by anticoagulants is a recent major focus of the United States (US) Department of Health and Human Services. This study quantified the risk of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH) among concomitant users of warfarin and individual antihyperlipidemics. METHODS: The authors conducted a high-dimensional propensity score-adjusted cohort study of new concomitant users of warfarin and an antihyperlipidemic, among US Medicaid beneficiaries from five states during 1999-2011. Exposure was defined by concomitant use of warfarin plus one of eight antihyperlipidemics. The primary outcome measure was a composite of GIB/ICH within the first 30days of concomitant use. As a secondary outcome measure, GIB/ICH was examined within the first 180days of concomitant use. RESULTS: Among 236,691 persons newly-exposed to warfarin and an antihyperlipidemic, the crude incidence of GIB/ICH was 13.2 (95% confidence interval 12.7 to 13.8) per 100person-years. Users were predominantly older, female, and Caucasian. Adjusted hazard ratios (aHRs) for warfarin and individual statins were consistent with no association. Warfarin+gemfibrozil was associated with an 80% increased risk of GIB/ICH within the first month of concomitant use (aHR=1.8, 1.4 to 2.4). Warfarin+fenofibrate was associated with a similar increased risk (aHR=1.8, 1.2 to 2.7), yet with an onset during the second month of concomitant use. CONCLUSIONS: Among warfarin-treated persons, the use of fibrates-but not statins-increases the risk of hospital presentation for GIB/ICH.
BACKGROUND: Drug interactions, particularly those involving warfarin, are a major clinical and public health problem. Minimizing serious bleeding caused by anticoagulants is a recent major focus of the United States (US) Department of Health and Human Services. This study quantified the risk of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH) among concomitant users of warfarin and individual antihyperlipidemics. METHODS: The authors conducted a high-dimensional propensity score-adjusted cohort study of new concomitant users of warfarin and an antihyperlipidemic, among US Medicaid beneficiaries from five states during 1999-2011. Exposure was defined by concomitant use of warfarin plus one of eight antihyperlipidemics. The primary outcome measure was a composite of GIB/ICH within the first 30days of concomitant use. As a secondary outcome measure, GIB/ICH was examined within the first 180days of concomitant use. RESULTS: Among 236,691 persons newly-exposed to warfarin and an antihyperlipidemic, the crude incidence of GIB/ICH was 13.2 (95% confidence interval 12.7 to 13.8) per 100person-years. Users were predominantly older, female, and Caucasian. Adjusted hazard ratios (aHRs) for warfarin and individual statins were consistent with no association. Warfarin+gemfibrozil was associated with an 80% increased risk of GIB/ICH within the first month of concomitant use (aHR=1.8, 1.4 to 2.4). Warfarin+fenofibrate was associated with a similar increased risk (aHR=1.8, 1.2 to 2.7), yet with an onset during the second month of concomitant use. CONCLUSIONS: Among warfarin-treated persons, the use of fibrates-but not statins-increases the risk of hospital presentation for GIB/ICH.
Authors: S Hennessy; C E Leonard; J J Gagne; J H Flory; X Han; C M Brensinger; W B Bilker Journal: Clin Pharmacol Ther Date: 2015-11-23 Impact factor: 6.875
Authors: Jerry H Gurwitz; Terry S Field; Leslie R Harrold; Jeffrey Rothschild; Kristin Debellis; Andrew C Seger; Cynthia Cadoret; Leslie S Fish; Lawrence Garber; Michael Kelleher; David W Bates Journal: JAMA Date: 2003-03-05 Impact factor: 56.272
Authors: H Schelleman; X Han; C M Brensinger; S K Quinney; W B Bilker; D A Flockhart; L Li; Sean Hennessy Journal: Br J Clin Pharmacol Date: 2014-09 Impact factor: 4.335
Authors: Jonas Wallvik; Anders Själander; Lars Johansson; Orjan Bjuhr; Jan-Håkan Jansson Journal: Scand J Prim Health Care Date: 2007-06 Impact factor: 2.581
Authors: Dima M Qato; G Caleb Alexander; Rena M Conti; Michael Johnson; Phil Schumm; Stacy Tessler Lindau Journal: JAMA Date: 2008-12-24 Impact factor: 56.272
Authors: Ryan M Carnahan; Joshua J Gagne; Christian Hampp; Charles E Leonard; Sengwee Toh; Candace C Fuller; Sean Hennessy; Laura Hou; Noelle M Cocoros; Genna Panucci; Tiffany Woodworth; Austin Cosgrove; Aarthi Iyer; Elizabeth A Chrischilles Journal: Pharmaceut Med Date: 2019-02
Authors: Charles E Leonard; Colleen M Brensinger; Warren B Bilker; Stephen E Kimmel; Heather J Whitaker; Sean Hennessy Journal: Sci Rep Date: 2017-12-21 Impact factor: 4.379
Authors: Nijole Bernaitis; Chi Keong Ching; Siew Chong Teo; Tony Badrick; Andrew K Davey; Julia Crilly; Shailendra Anoopkumar-Dukie Journal: J Clin Med Date: 2018-05-01 Impact factor: 4.241
Authors: Hassan Alwafi; Li Wei; Abdallah Y Naser; Pajaree Mongkhon; Gary Tse; Kenneth K C Man; J Simon Bell; Jenni Ilomaki; Gang Fang; Ian C K Wong Journal: BMJ Open Date: 2020-05-15 Impact factor: 2.692