Abstract
Prescribers’ concern regarding falls resulting in intracranial hemorrhage is often cited as a justification for under-utilization of oral anticoagulation. We evaluated the safety and effectiveness of oral factor Xa inhibitors versus warfarin in nonvalvular atrial fibrillation patients at high-risk for falls. Using MarketScan claims from 11/2012-3/2017, we identified adult, oral anticoagulation-naïve, new-initiators of oral factor Xa inhibitors or warfarin with nonvalvular atrial fibrillation, ≥ 12 months of insurance coverage prior to starting oral anticoagulation and a predicted 2-year risk of falls ≥ 15%. Differences in baseline covariates between cohorts were balanced using inverse probability-of-treatment weights based on propensity scores. Hazard ratios (HRs) and 95% confidence intervals (CIs) for intracranial hemorrhage and stroke or systemic embolism were estimated. Among 25,144 nonvalvular atrial fibrillation patients at high-risk for falls (observed fall rate = 11.8%/person-year), oral factor Xa inhibitor use was associated with a 43% (95% CI = 5–65%) reduced hazard of intracranial hemorrhage compared to warfarin. Oral factor Xa inhibitors did not significantly reduce the hazard of stroke or systemic embolism versus warfarin (HR = 0.86, 95% CI = 0.66–1.11). Findings for the intracranial hemorrhage and stroke or systemic embolism endpoints were similar when apixaban and rivaroxaban were evaluated separately versus warfarin (p-interaction ≥ 0.64 for all). Oral factor Xa inhibitors reduced patients’ risk of intracranial hemorrhage and were at least as effective in preventing stroke or systemic embolism as warfarin in nonvalvular atrial fibrillation patients at high-risk for falls.
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Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, ESC Scientific Document Group (2016) 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 37:2893–2962
Homer ML, Palmer NP, Fox KP, Armstrong J, Mandl KD (2017) Predicting falls in people aged 65 years and older from insurance claims. Am J Med 130:744.e17–744.e23
Kakkar AK, Mueller I, Bassand JP, Fitzmaurice DA, Goldhaber SZ, Goto S, Haas S, Hacke W, Lip GY, Mantovani LG, Turpie AG, van Eickels M, Misselwitz F, Rushton-Smith S, Kayani G, Wilkinson P, Verheugt FW, GARFIELD Registry Investigators (2013) Risk profiles and antithrombotic treatment of patients newly diagnosed with atrial fibrillation at risk of stroke: perspectives from the international, observational, prospective GARFIELD registry. PLoS ONE 8:e63479
Hansen L. The Truven Health MarketScan Databases for life sciences researchers. https://truvenhealth.com/Portals/0/Assets/2017-MarketScan-Databases-Life-Sciences-Researchers-WP.pdf. Accessed 11 Jan, 2019
Caetano PA, Lam JM, Morgan SG (2006) Toward a standard definition and measurement of persistence with drug therapy: examples from research on statin and antihypertensive utilization. Clin Ther 28:1411–1424
Austin PC (2011) An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res 46:399–424
Altman DG, Bland JM (2003) Interaction revisited: the difference between two estimates. BMJ 326:219
Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B 57:289–300
Xiang CL, Gong YZ, Zeng LJ, Wang R, Kea S, Chaudhary N, Tu RH, He Y (2016) Efficacy and safety of oral direct factor Xa inhibitors versus warfarin in patients with atrial fibrillation: a meta-analysis of randomized controlled trials. Acta Cardiol 71:349–357
Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L, ARISTOTLE Committees and Investigators (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365:981–992
Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM, ENGAGE AF-TIMI 48 Investigators (2013) Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 369:2093–2104
Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM, ROCKET AF Investigators (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365:883–891
Palumbo P, Palmerini L, Bandinelli S et al (2015) Fall risk assessment tools for elderly living in the community: can we do better? PLoS ONE 10:e0146247
Melgaard L, Gorst-Rasmussen A, Lane DA et al (2015) Assessment of the CHA2DS2-VASc score in predicting ischemic stroke, thromboembolism, and death in patients with heart failure with and without atrial fibrillation. JAMA 10:1–9
Gandhi SK, Salmon W, Kong SX, Zhao SZ (1999) Administrative databases and outcomes assessment: an overview of issues and potential utility. J Manag Care Spec Pharm 5:215–222
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This study was funded by Bayer AG, Berlin, Germany
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CIC has received Grant funding and consultancy fees from Janssen Scientific Affairs, LLC; Bayer Pharma AG; and Boehringer-Ingelheim Pharmaceuticals, Inc. MJA has received consultancy fees and honoraria from and is on the speakers bureau of Genentech, Janssen Pharmaceuticals, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, and Medscape; consultancy fees and honoraria from Nestle, Daiichi Sankyo and Portola; honoraria from and is on the speakers bureau of Chiesi USA, Inc.; and patents/royalties from Duke University. No other authors have conflicts germane to this manuscript.
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Miao, B., Alberts, M.J., Bunz, T.J. et al. Safety and effectiveness of oral factor Xa inhibitors versus warfarin in nonvalvular atrial fibrillation patients at high-risk for falls. J Thromb Thrombolysis 48, 366–372 (2019). https://doi.org/10.1007/s11239-019-01898-7
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DOI: https://doi.org/10.1007/s11239-019-01898-7