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Dabigatran Versus Rivaroxaban for Secondary Stroke Prevention in Patients with Atrial Fibrillation Rehabilitated in Skilled Nursing Facilities

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Abstract

Background

Thromboembolic and bleeding risk are elevated in older patients with atrial fibrillation and prior stroke. We compared dabigatran with rivaroxaban for secondary prevention in a national population after skilled nursing facility (SNF) discharge.

Methods

Medicare fee-for-service beneficiaries aged ≥ 65 years with atrial fibrillation hospitalized for ischemic stroke (November 2011–October 2013) and subsequently admitted to an SNF were studied. Dabigatran (n = 332) and rivaroxaban users (n = 378) were compared in a retrospective, active comparator, new-user cohort. The index medication claim occurred within 120 days after hospital discharge and exposure continued until a 14-day treatment gap (‘as treated’). The primary net clinical benefit outcome was the time to recurrent stroke, transient ischemic attack, intracranial hemorrhage, extracranial bleed, myocardial infarction, venous thromboembolism, or death. All-cause mortality was evaluated separately as a secondary outcome. Multivariable adjusted Cox models stratified by dosage estimated hazard ratios (aHR).

Results

Among those receiving low dosages, the crude composite event rate was 40.4/100 person-years among dabigatran users and 33.7/100 person-years among rivaroxaban users. The composite outcome [aHR 1.48; 95% confidence interval (CI) 0.87–2.51] and all-cause mortality (aHR 1.67; 95% CI 0.84–3.31) rates were higher among low-dose dabigatran users. For those receiving standard doses, the crude composite event rates were 19.5/100 person-years for dabigatran users and 37.1/100 person-years for rivaroxaban users. Although no difference in mortality was observed, the composite outcome rate was lower among standard-dose dabigatran users (aHR 0.65; 95% CI 0.36–1.15).

Conclusions

In older adults treated with direct-acting oral anticoagulants after ischemic stroke, outcome rates varied considerably by drug and dosage.

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References

  1. Rocca WA, Boyd CM, Grossardt BR, Bobo WV, Finney Rutten LJ, Roger VL, et al. The prevalence of multimorbidity in a geographically defined American population: patterns by age, sex, and ethnicity. Mayo Clin Proc. 2014;89:1336–49.

    Article  Google Scholar 

  2. Charlesworth CJ, Smit E, Lee DSH, Alramadhan F, Odden MC. Polypharmacy among adults aged 65 years and older in the United States: 1988–2010. J Gerontol Ser A Biol Sci Med Sci. 2015;70:989–95.

    Article  CAS  Google Scholar 

  3. Russo T, Felzani G, Marini C. Stroke in the very old: a systematic review of studies on incidence, outcome, and resource use. J Aging Res. 2011;2011:108785.

    Article  Google Scholar 

  4. Buntin MB, Colla CH, Deb P, Sood N, Escarce JJ. Medicare spending and outcomes after postacute care for stroke and hip fracture. Med Care. 2010;48:776–84.

    Article  Google Scholar 

  5. Patel PA, Zhao X, Fonarow GC, Lytle BL, Smith EE, Xian Y, et al. Novel oral anticoagulant use among patients with atrial fibrillation hospitalized with ischemic stroke or transient ischemic attack. Circ Cardiovasc Qual Outcomes. 2015;8:383–92.

    Article  Google Scholar 

  6. Sardar P, Chatterjee S, Wu WC, Lichstein E, Ghosh J, Aikat S, et al. New oral anticoagulants are not superior to warfarin in secondary prevention of stroke or transient ischemic attacks, but lower the risk of intracranial bleeding: insights from a meta-analysis and indirect treatment comparisons. PLoS One. 2013;8:e77694.

    Article  CAS  Google Scholar 

  7. Rasmussen LH, Larsen TB, Graungaard T, Skjoth F, Lip GYH. Primary and secondary prevention with new oral anticoagulant drugs for stroke prevention in atrial fibrillation: indirect comparison analysis. BMJ. 2012;345:e7097.

    Article  Google Scholar 

  8. Hernandez I, Zhang Y. Comparing stroke and bleeding with rivaroxaban and dabigatran in atrial fibrillation: analysis of the us medicare part D data. Am J Cardiovasc Drugs. 2017;17:37–47.

    Article  CAS  Google Scholar 

  9. Graham DJ, Reichman ME, Wernecke M, Hsueh YH, Izem R, Southworth MR. Stroke, bleeding, and mortality risks in elderly medicare beneficiaries treated with dabigatran or rivaroxaban for nonvalvular atrial fibrillation. JAMA Intern Med. 2016;176:1662–71.

    Article  Google Scholar 

  10. Kanai Y, Oguro H, Tahara N, Matsuda H, Takayoshi H, Mitaki S, et al. Analysis of recurrent stroke volume and prognosis between warfarin and four non-vitamin k antagonist oral anticoagulants’ administration for secondary prevention of stroke. J Stroke Cerebrovasc Dis. 2018;27(2):338–45.

    Article  Google Scholar 

  11. Nakase T, Moroi J, Ishikawa T. Outcome of secondary stroke prevention in patients taking non-vitamin K antagonist oral anticoagulants. J Stroke Cerebrovasc Dis. 2018;27(5):1174–7.

    Article  Google Scholar 

  12. Saliba D, Buchanan J. Making the investment count: revision of the minimum data set for nursing homes, MDS 3.0. J Am Med Dir Assoc. 2012;13(7):602–10.

    Article  Google Scholar 

  13. Lund JL, Richardson DB, Stürmer T. The active comparator, new user study design in pharmacoepidemiology: historical foundations and contemporary application. Curr Epidemiol Rep. 2015;2(4):221–8.

    Article  Google Scholar 

  14. Kumamaru H, Judd SE, Curtis JR, Ramachandran R, Hardy NC, Rhodes JD, et al. Validity of claims-based stroke algorithms in contemporary medicare data: reasons for geographic and racial differences in stroke (REGARDS) study linked with medicare claims. Circ Cardiovasc Qual Outcomes. 2014;7:611–9.

    Article  Google Scholar 

  15. Steinberg BA, Shrader P, Thomas L, Ansell J, Fonarow GC, Gersh BJ, ORBIT-AF Investigators and Patients, et al. Off-label dosing of non-vitamin K antagonist oral anticoagulants and adverse outcomes: the ORBIT-AF II registry. J Am Coll Cardiol. 2016;68:2597–604.

    Article  CAS  Google Scholar 

  16. Yao X, Shah ND, Sangaralingham LR, Gersh BJ, Noseworthy PA. Non-vitamin K antagonist oral anticoagulant dosing in patients with atrial fibrillation and renal dysfunction. J Am Coll Cardiol. 2017;69:2779–90.

    Article  CAS  Google Scholar 

  17. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, RE-LY Steering Committee and Investigators, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.

    Article  CAS  Google Scholar 

  18. Cunningham A, Stein CM, Chung CP, Daugherty JR, Smalley WE, Ray WA. An automated database case definition for serious bleeding related to oral anticoagulant use. Pharmacoepidemiol Drug Saf. 2011;20:560–6.

    Article  Google Scholar 

  19. White RH, Garcia M, Sadeghi B, Tancredi DJ, Zrelak P, Cuny J, et al. Evaluation of the predictive value of ICD-9-CM coded administrative data for venous thromboembolism in the United States. Thromb Res. 2010;126(1):61–7.

    Article  CAS  Google Scholar 

  20. Kiyota Y, Schneeweiss S, Glynn RJ, Cannuscio CC, Avorn J, Solomon DH. Accuracy of medicare claims-based diagnosis of acute myocardial infarction: estimating positive predictive value on the basis of review of hospital records. Am Heart J. 2004;148:99–104.

    Article  Google Scholar 

  21. Pisters R, Lane DA, Nieuwlaat R, De Vos CB, Crijns HJGM, Lip GYH. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the euro heart survey. Chest. 2010;138:1093–100.

    Article  Google Scholar 

  22. Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes results from the national registry of atrial fibrillation. JAMA. 2001;285:2864–70.

    Article  CAS  Google Scholar 

  23. Winkelmayer WC, Schneeweiss S, Mogun H, Patrick AR, Avorn J, Solomon DH. Identification of individuals with CKD from medicare claims data: a validation study. Am J Kidney Dis. 2005;46:225–32.

    Article  Google Scholar 

  24. Thomas KS, Dosa D, Wysocki A, Mor V. The Minimum Data Set 3.0 Cognitive Function Scale. Med Care. 2017;55(9):e68–72.

    Article  Google Scholar 

  25. Centers for Medicare and Medicaid Services. MDS 3.0 RAI Manual. https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/NursingHomeQualityInits/MDS30RAIManual.html. Published October 1, 2016. Accessed 1 Sept 2017.

  26. Shah S, Vanclay F, Cooper B, Duckworth D, Dombovy M. Improving the sensitivity of the Barthel Index for stroke rehabilitation. J Clin Epidemiol. 1989;42:703–9.

    Article  CAS  Google Scholar 

  27. Raparelli V, Proietti M, Cangemi R, Lip GY, Lane DA, Basili S. Adherence to oral anticoagulant therapy in patients with atrial fibrillation. Focus on non-vitamin K antagonist oral anticoagulants. Thromb Haemost. 2017;117:209–18.

    Article  Google Scholar 

  28. Steinberg BA, Shrader P, Thomas L, Ansell J, Fonarow GC, Gersh BJ, et al. Factors associated with non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with new-onset atrial fibrillation: results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II (ORBIT-AF II). Am Heart J. 2017;189:40–7.

    Article  CAS  Google Scholar 

  29. Lichtman JH, Naert L, Allen NB, Watanabe E, Jones SB, Barry LC, et al. Use of antithrombotic medications among elderly ischemic stroke patients. Circ Cardiovasc Qual Outcomes. 2011;4:30–8.

    Article  Google Scholar 

  30. Ghaswalla PK, Harpe SE, Slattum PW. Warfarin use in nursing home residents: results from the 2004 national nursing home survey. Am J Geriatr Pharmacother. 2012;10(25–36):e2.

    Google Scholar 

  31. MacLean S, Mulla S, Akl EA, Jankowski M, Vandvik PO, Ebrahim S, et al. Patient values and preferences in decision making for antithrombotic therapy: a systematic review: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e1S–23S.

    Article  CAS  Google Scholar 

  32. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, ROCKET AF Investigators, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.

    Article  CAS  Google Scholar 

  33. Coleman CI, Peacock WF, Bunz TJ, Alberts MJ. Effectiveness and safety of apixaban, dabigatran, and rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and previous stroke or transient ischemic attack. Stroke. 2017;48:2142–9.

    Article  CAS  Google Scholar 

  34. Nielsen PB, Skjøth F, Søgaard M, Kjældgaard JN, Lip GY, et al. Effectiveness and safety of reduced dose non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study. BMJ. 2017;10(356):j510.

    Article  Google Scholar 

  35. Pradaxa [package insert]. Ridgefield, CT: Boehringer Ingelheim; 2012. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022512s000lbl.pdf. Accessed 25 June 2017.

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Authors and Affiliations

  1. Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, USA

    Matthew Alcusky, Jennifer Tjia, Robert J. Goldberg, David D. McManus & Kate L. Lapane

  2. Department of Pharmacy Practice, College of Pharmacy, University of Rhode Island, Kingston, RI, USA

    Anne L. Hume

  3. Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Marc Fisher

  4. Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA

    David D. McManus

Authors
  1. Matthew Alcusky
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  2. Anne L. Hume
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  3. Marc Fisher
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  4. Jennifer Tjia
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  7. Kate L. Lapane
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Corresponding author

Correspondence to Matthew Alcusky.

Ethics declarations

The University of Massachusetts Medical School Institutional Review Board approved this study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of research formal consent is not required.

Funding

At the time the study was conducted, Dr Alcusky was funded by the National Center for Advancing Translational Sciences (TL1TR001454). Dr McManus was funded by the National Heart, Lung, and Blood Institute (RO1HL126911, RO1HL135219, RO1HL136660, R15HL121761). Partial support for Dr Goldberg was provided by the National Heart, Lung, and Blood Institute (1R01HL126911-01A1, 5R01HL125089-02, 5R01HL115295-05).

Conflict of interest

Dr. Tjia is a consultant for CVS Health. Dr. Alcusky, Dr. Goldberg, Dr. Fisher, Dr. Lapane, and Dr. Hume have no interests to disclose.

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Alcusky, M., Hume, A.L., Fisher, M. et al. Dabigatran Versus Rivaroxaban for Secondary Stroke Prevention in Patients with Atrial Fibrillation Rehabilitated in Skilled Nursing Facilities. Drugs Aging 35, 1089–1098 (2018). https://doi.org/10.1007/s40266-018-0610-y

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  • DOI: https://doi.org/10.1007/s40266-018-0610-y

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