Matthew Alcusky1, Jennifer Tjia2, David D McManus2,3, Anne L Hume4, Marc Fisher5, Kate L Lapane2. 1. Department of Population and Quantitative Health Sciences , University of Massachusetts Medical School, Worcester, MA, USA. matthew.alcusky@umassmed.edu. 2. Department of Population and Quantitative Health Sciences , University of Massachusetts Medical School, Worcester, MA, USA. 3. Department of Medicine, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, MA, USA. 4. Department of Pharmacy Practice, College of Pharmacy, University of Rhode Island, Kingston, RI, USA. 5. Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Abstract
BACKGROUND: Research comparing direct-acting oral anticoagulants (DOACs) to warfarin has excluded nursing home residents, a vulnerable and high-risk population. OBJECTIVE: To compare the safety and effectiveness of DOACs versus warfarin. DESIGN: New-user cohort study (2011-2016). PATIENTS: US nursing home residents aged > 65 years with non-valvular atrial fibrillation enrolled in fee-for-service Medicare for > 6 months. EXPOSURES: Initiators of DOACs (2881 apixaban, 1289 dabigatran, 3735 rivaroxaban) were 1:1 propensity matched to warfarin initiators. MAIN MEASURES: Outcomes included ischemic stroke or transient ischemic attack (i.e., ischemic cerebrovascular event), bleeding (extracranial or intracranial), other vascular events, death, and a composite of all outcomes. Absolute rate differences (RD) and cause-specific hazard ratios (HR) with 95% confidence intervals (CI) were estimated. Subgroup analyses were performed by alignment of DOAC dosing with labeling. KEY RESULTS: Median age (84 years), CHA2DS2-Vasc (5), and ATRIA risk scores (3) were similar across medications. Clinical outcome rates were similar for dabigatran and rivaroxaban users versus warfarin users. However, ischemic cerebrovascular event rates were higher among dabigatran and rivaroxaban users that received reduced dosages without an indication. Overall, apixaban users had higher ischemic cerebrovascular event rates (HR 1.86; 95% CI 1.00-3.45) and lower bleeding rates (HR 0.66; 95% CI 0.49-0.88), but outcome rates varied by dosing alignment. Mortality rates (per 100 person-years) were lower for apixaban (RDs - 9.30; 95% CI - 13.18 to - 5.42), dabigatran (RDs - 10.79; 95% CI - 14.98 to - 6.60), and rivaroxaban (RDs - 8.92; 95% CI - 12.01 to - 5.83) versus warfarin; composite outcome findings were similar. CONCLUSIONS: Among US nursing home residents, the DOACs were each associated with lower mortality versus warfarin. Misaligned DOAC dosing was common in nursing homes and was associated with clinical and mortality outcomes. Overall, DOAC users had lower rates of adverse outcomes including mortality compared with warfarin users.
BACKGROUND: Research comparing direct-acting oral anticoagulants (DOACs) to warfarin has excluded nursing home residents, a vulnerable and high-risk population. OBJECTIVE: To compare the safety and effectiveness of DOACs versus warfarin. DESIGN: New-user cohort study (2011-2016). PATIENTS: US nursing home residents aged > 65 years with non-valvular atrial fibrillation enrolled in fee-for-service Medicare for > 6 months. EXPOSURES: Initiators of DOACs (2881 apixaban, 1289 dabigatran, 3735 rivaroxaban) were 1:1 propensity matched to warfarin initiators. MAIN MEASURES: Outcomes included ischemic stroke or transient ischemic attack (i.e., ischemic cerebrovascular event), bleeding (extracranial or intracranial), other vascular events, death, and a composite of all outcomes. Absolute rate differences (RD) and cause-specific hazard ratios (HR) with 95% confidence intervals (CI) were estimated. Subgroup analyses were performed by alignment of DOAC dosing with labeling. KEY RESULTS: Median age (84 years), CHA2DS2-Vasc (5), and ATRIA risk scores (3) were similar across medications. Clinical outcome rates were similar for dabigatran and rivaroxaban users versus warfarin users. However, ischemic cerebrovascular event rates were higher among dabigatran and rivaroxaban users that received reduced dosages without an indication. Overall, apixaban users had higher ischemic cerebrovascular event rates (HR 1.86; 95% CI 1.00-3.45) and lower bleeding rates (HR 0.66; 95% CI 0.49-0.88), but outcome rates varied by dosing alignment. Mortality rates (per 100 person-years) were lower for apixaban (RDs - 9.30; 95% CI - 13.18 to - 5.42), dabigatran (RDs - 10.79; 95% CI - 14.98 to - 6.60), and rivaroxaban (RDs - 8.92; 95% CI - 12.01 to - 5.83) versus warfarin; composite outcome findings were similar. CONCLUSIONS: Among US nursing home residents, the DOACs were each associated with lower mortality versus warfarin. Misaligned DOAC dosing was common in nursing homes and was associated with clinical and mortality outcomes. Overall, DOAC users had lower rates of adverse outcomes including mortality compared with warfarin users.
Entities:
Keywords:
anticoagulants; atrial fibrillation; comparative effectiveness; nursing homes
Authors: Manesh R Patel; Kenneth W Mahaffey; Jyotsna Garg; Guohua Pan; Daniel E Singer; Werner Hacke; Günter Breithardt; Jonathan L Halperin; Graeme J Hankey; Jonathan P Piccini; Richard C Becker; Christopher C Nessel; John F Paolini; Scott D Berkowitz; Keith A A Fox; Robert M Califf Journal: N Engl J Med Date: 2011-08-10 Impact factor: 91.245
Authors: Craig T January; L Samuel Wann; Hugh Calkins; Lin Y Chen; Joaquin E Cigarroa; Joseph C Cleveland; Patrick T Ellinor; Michael D Ezekowitz; Michael E Field; Karen L Furie; Paul A Heidenreich; Katherine T Murray; Julie B Shea; Cynthia M Tracy; Clyde W Yancy Journal: J Am Coll Cardiol Date: 2019-01-28 Impact factor: 24.094
Authors: Richard H White; Martina Garcia; Banafsheh Sadeghi; Daniel J Tancredi; Patricia Zrelak; Joanne Cuny; Pradeep Sama; Harriet Gammon; Stephen Schmaltz; Patrick S Romano Journal: Thromb Res Date: 2010-04-28 Impact factor: 3.944
Authors: Benjamin A Steinberg; Peter Shrader; Laine Thomas; Jack Ansell; Gregg C Fonarow; Bernard J Gersh; Elaine Hylek; Peter R Kowey; Kenneth W Mahaffey; Emily C O'Brien; Daniel E Singer; Eric D Peterson; Jonathan P Piccini Journal: Am Heart J Date: 2017-04-04 Impact factor: 4.749
Authors: Amanda R Patrick; Sebastian Schneeweiss; M Alan Brookhart; Robert J Glynn; Kenneth J Rothman; Jerry Avorn; Til Stürmer Journal: Pharmacoepidemiol Drug Saf Date: 2011-03-10 Impact factor: 2.890
Authors: Jonathan Mant; F D Richard Hobbs; Kate Fletcher; Andrea Roalfe; David Fitzmaurice; Gregory Y H Lip; Ellen Murray Journal: Lancet Date: 2007-08-11 Impact factor: 79.321
Authors: Clara Bonanad; Francisca Esteve-Claramunt; Sergio García-Blas; Ana Ayesta; Pablo Díez-Villanueva; Jose-Ángel Pérez-Rivera; José Luis Ferreiro; Joaquim Cánoves; Francisco López-Fornás; Albert Ariza Solé; Sergio Raposerias; David Vivas; Regina Blanco; Daznia Bompart Berroterán; Alberto Cordero; Julio Núñez; Lorenzo Fácila; Iván J Núñez-Gil; José Luis Górriz; Vicente Bodí; Manuel Martínez-Selles; Juan Miguel Ruiz Nodar; Francisco Javier Chorro Journal: J Clin Med Date: 2022-05-26 Impact factor: 4.964
Authors: Benjamin J R Buckley; Deirdre A Lane; Peter Calvert; Juqian Zhang; David Gent; C Daniel Mullins; Paul Dorian; Shun Kohsaka; Stefan H Hohnloser; Gregory Y H Lip Journal: J Clin Med Date: 2022-06-30 Impact factor: 4.964