Outcomes Associated With Apixaban Use in Patients With End-Stage Kidney Disease and Atrial Fibrillation in the United States

Konstantinos C. Siontis, Xiaosong Zhang, Ashley Eckard, Nicole Bhave, Douglas E. Schaubel, Kevin He, Anca Tilea, Austin G. Stack, Rajesh Balkrishnan, Xiaoxi Yao, Peter Noseworthy, Nilay D Shah, Rajiv Saran, Brahmajee K. Nallamothu

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Abstract

BACKGROUND: Patients with end-stage kidney disease (ESKD) on dialysis were excluded from clinical trials of direct oral anticoagulants for atrial fibrillation (AF). Recent data have raised concerns regarding the safety of dabigatran and rivaroxaban, but apixaban has not been evaluated despite current labeling supporting its use in this population. The goal of this study was to determine patterns of apixaban use and its associated outcomes in dialysis-dependent patients with ESKD and AF.

METHODS: We performed a retrospective cohort study of Medicare beneficiaries included in the United States Renal Data System (October 2010 to December 2015). Eligible patients were those with ESKD and AF undergoing dialysis who initiated treatment with an oral anticoagulant. Because of the small number of dabigatran and rivaroxaban users, outcomes were only assessed in patients treated with apixaban or warfarin. Apixaban and warfarin patients were matched (1:3) based on prognostic score. Differences between groups in survival free of stroke or systemic embolism, major bleeding, gastrointestinal bleeding, intracranial bleeding, and death were assessed using Kaplan-Meier analyses. Hazard ratios (HRs) and 95% CIs were derived from Cox regression analyses.

RESULTS: The study population consisted of 25 523 patients (45.7% women; 68.2±11.9 years of age), including 2351 patients on apixaban and 23 172 patients on warfarin. An annual increase in apixaban prescriptions was observed after its marketing approval at the end of 2012, such that 26.6% of new anticoagulant prescriptions in 2015 were for apixaban. In matched cohorts, there was no difference in the risks of stroke/systemic embolism between apixaban and warfarin (HR, 0.88; 95% CI, 0.69-1.12; P=0.29), but apixaban was associated with a significantly lower risk of major bleeding (HR, 0.72; 95% CI, 0.59-0.87; P<0.001). In sensitivity analyses, standard-dose apixaban (5 mg twice a day; n=1034) was associated with significantly lower risks of stroke/systemic embolism and death as compared with either reduced-dose apixaban (2.5 mg twice a day; n=1317; HR, 0.61; 95% CI, 0.37-0.98; P=0.04 for stroke/systemic embolism; HR, 0.64; 95% CI, 0.45-0.92; P=0.01 for death) or warfarin (HR, 0.64; 95% CI, 0.42-0.97; P=0.04 for stroke/systemic embolism; HR, 0.63; 95% CI, 0.46-0.85; P=0.003 for death).

CONCLUSIONS: Among patients with ESKD and AF on dialysis, apixaban use may be associated with a lower risk of major bleeding compared with warfarin, with a standard 5 mg twice a day dose also associated with reductions in thromboembolic and mortality risk.

Original languageEnglish (US)
Pages (from-to)1519-1529
Number of pages11
JournalCirculation
Volume138
Issue number15
DOIs
StatePublished - Oct 9 2018

Fingerprint

Atrial Fibrillation
Chronic Kidney Failure
Warfarin
Embolism
Stroke
Hemorrhage
Dialysis
Anticoagulants
Prescriptions
apixaban
Kaplan-Meier Estimate
Medicare
Marketing
Information Systems
Population
Cohort Studies
Retrospective Studies
Regression Analysis
Clinical Trials
Kidney

Keywords

  • anticoagulation
  • atrial fibrillation
  • bleeding
  • dialysis
  • stroke prevention

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Siontis, K. C., Zhang, X., Eckard, A., Bhave, N., Schaubel, D. E., He, K., ... Nallamothu, B. K. (2018). Outcomes Associated With Apixaban Use in Patients With End-Stage Kidney Disease and Atrial Fibrillation in the United States. Circulation, 138(15), 1519-1529. https://doi.org/10.1161/CIRCULATIONAHA.118.035418

Outcomes Associated With Apixaban Use in Patients With End-Stage Kidney Disease and Atrial Fibrillation in the United States. / Siontis, Konstantinos C.; Zhang, Xiaosong; Eckard, Ashley; Bhave, Nicole; Schaubel, Douglas E.; He, Kevin; Tilea, Anca; Stack, Austin G.; Balkrishnan, Rajesh; Yao, Xiaoxi; Noseworthy, Peter; Shah, Nilay D; Saran, Rajiv; Nallamothu, Brahmajee K.

In: Circulation, Vol. 138, No. 15, 09.10.2018, p. 1519-1529.

Research output: Contribution to journalArticle

Siontis, KC, Zhang, X, Eckard, A, Bhave, N, Schaubel, DE, He, K, Tilea, A, Stack, AG, Balkrishnan, R, Yao, X, Noseworthy, P, Shah, ND, Saran, R & Nallamothu, BK 2018, 'Outcomes Associated With Apixaban Use in Patients With End-Stage Kidney Disease and Atrial Fibrillation in the United States', Circulation, vol. 138, no. 15, pp. 1519-1529. https://doi.org/10.1161/CIRCULATIONAHA.118.035418
Siontis, Konstantinos C. ; Zhang, Xiaosong ; Eckard, Ashley ; Bhave, Nicole ; Schaubel, Douglas E. ; He, Kevin ; Tilea, Anca ; Stack, Austin G. ; Balkrishnan, Rajesh ; Yao, Xiaoxi ; Noseworthy, Peter ; Shah, Nilay D ; Saran, Rajiv ; Nallamothu, Brahmajee K. / Outcomes Associated With Apixaban Use in Patients With End-Stage Kidney Disease and Atrial Fibrillation in the United States. In: Circulation. 2018 ; Vol. 138, No. 15. pp. 1519-1529.
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title = "Outcomes Associated With Apixaban Use in Patients With End-Stage Kidney Disease and Atrial Fibrillation in the United States",
abstract = "BACKGROUND: Patients with end-stage kidney disease (ESKD) on dialysis were excluded from clinical trials of direct oral anticoagulants for atrial fibrillation (AF). Recent data have raised concerns regarding the safety of dabigatran and rivaroxaban, but apixaban has not been evaluated despite current labeling supporting its use in this population. The goal of this study was to determine patterns of apixaban use and its associated outcomes in dialysis-dependent patients with ESKD and AF.METHODS: We performed a retrospective cohort study of Medicare beneficiaries included in the United States Renal Data System (October 2010 to December 2015). Eligible patients were those with ESKD and AF undergoing dialysis who initiated treatment with an oral anticoagulant. Because of the small number of dabigatran and rivaroxaban users, outcomes were only assessed in patients treated with apixaban or warfarin. Apixaban and warfarin patients were matched (1:3) based on prognostic score. Differences between groups in survival free of stroke or systemic embolism, major bleeding, gastrointestinal bleeding, intracranial bleeding, and death were assessed using Kaplan-Meier analyses. Hazard ratios (HRs) and 95{\%} CIs were derived from Cox regression analyses.RESULTS: The study population consisted of 25 523 patients (45.7{\%} women; 68.2±11.9 years of age), including 2351 patients on apixaban and 23 172 patients on warfarin. An annual increase in apixaban prescriptions was observed after its marketing approval at the end of 2012, such that 26.6{\%} of new anticoagulant prescriptions in 2015 were for apixaban. In matched cohorts, there was no difference in the risks of stroke/systemic embolism between apixaban and warfarin (HR, 0.88; 95{\%} CI, 0.69-1.12; P=0.29), but apixaban was associated with a significantly lower risk of major bleeding (HR, 0.72; 95{\%} CI, 0.59-0.87; P<0.001). In sensitivity analyses, standard-dose apixaban (5 mg twice a day; n=1034) was associated with significantly lower risks of stroke/systemic embolism and death as compared with either reduced-dose apixaban (2.5 mg twice a day; n=1317; HR, 0.61; 95{\%} CI, 0.37-0.98; P=0.04 for stroke/systemic embolism; HR, 0.64; 95{\%} CI, 0.45-0.92; P=0.01 for death) or warfarin (HR, 0.64; 95{\%} CI, 0.42-0.97; P=0.04 for stroke/systemic embolism; HR, 0.63; 95{\%} CI, 0.46-0.85; P=0.003 for death).CONCLUSIONS: Among patients with ESKD and AF on dialysis, apixaban use may be associated with a lower risk of major bleeding compared with warfarin, with a standard 5 mg twice a day dose also associated with reductions in thromboembolic and mortality risk.",
keywords = "anticoagulation, atrial fibrillation, bleeding, dialysis, stroke prevention",
author = "Siontis, {Konstantinos C.} and Xiaosong Zhang and Ashley Eckard and Nicole Bhave and Schaubel, {Douglas E.} and Kevin He and Anca Tilea and Stack, {Austin G.} and Rajesh Balkrishnan and Xiaoxi Yao and Peter Noseworthy and Shah, {Nilay D} and Rajiv Saran and Nallamothu, {Brahmajee K.}",
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TY - JOUR

T1 - Outcomes Associated With Apixaban Use in Patients With End-Stage Kidney Disease and Atrial Fibrillation in the United States

AU - Siontis, Konstantinos C.

AU - Zhang, Xiaosong

AU - Eckard, Ashley

AU - Bhave, Nicole

AU - Schaubel, Douglas E.

AU - He, Kevin

AU - Tilea, Anca

AU - Stack, Austin G.

AU - Balkrishnan, Rajesh

AU - Yao, Xiaoxi

AU - Noseworthy, Peter

AU - Shah, Nilay D

AU - Saran, Rajiv

AU - Nallamothu, Brahmajee K.

PY - 2018/10/9

Y1 - 2018/10/9

N2 - BACKGROUND: Patients with end-stage kidney disease (ESKD) on dialysis were excluded from clinical trials of direct oral anticoagulants for atrial fibrillation (AF). Recent data have raised concerns regarding the safety of dabigatran and rivaroxaban, but apixaban has not been evaluated despite current labeling supporting its use in this population. The goal of this study was to determine patterns of apixaban use and its associated outcomes in dialysis-dependent patients with ESKD and AF.METHODS: We performed a retrospective cohort study of Medicare beneficiaries included in the United States Renal Data System (October 2010 to December 2015). Eligible patients were those with ESKD and AF undergoing dialysis who initiated treatment with an oral anticoagulant. Because of the small number of dabigatran and rivaroxaban users, outcomes were only assessed in patients treated with apixaban or warfarin. Apixaban and warfarin patients were matched (1:3) based on prognostic score. Differences between groups in survival free of stroke or systemic embolism, major bleeding, gastrointestinal bleeding, intracranial bleeding, and death were assessed using Kaplan-Meier analyses. Hazard ratios (HRs) and 95% CIs were derived from Cox regression analyses.RESULTS: The study population consisted of 25 523 patients (45.7% women; 68.2±11.9 years of age), including 2351 patients on apixaban and 23 172 patients on warfarin. An annual increase in apixaban prescriptions was observed after its marketing approval at the end of 2012, such that 26.6% of new anticoagulant prescriptions in 2015 were for apixaban. In matched cohorts, there was no difference in the risks of stroke/systemic embolism between apixaban and warfarin (HR, 0.88; 95% CI, 0.69-1.12; P=0.29), but apixaban was associated with a significantly lower risk of major bleeding (HR, 0.72; 95% CI, 0.59-0.87; P<0.001). In sensitivity analyses, standard-dose apixaban (5 mg twice a day; n=1034) was associated with significantly lower risks of stroke/systemic embolism and death as compared with either reduced-dose apixaban (2.5 mg twice a day; n=1317; HR, 0.61; 95% CI, 0.37-0.98; P=0.04 for stroke/systemic embolism; HR, 0.64; 95% CI, 0.45-0.92; P=0.01 for death) or warfarin (HR, 0.64; 95% CI, 0.42-0.97; P=0.04 for stroke/systemic embolism; HR, 0.63; 95% CI, 0.46-0.85; P=0.003 for death).CONCLUSIONS: Among patients with ESKD and AF on dialysis, apixaban use may be associated with a lower risk of major bleeding compared with warfarin, with a standard 5 mg twice a day dose also associated with reductions in thromboembolic and mortality risk.

AB - BACKGROUND: Patients with end-stage kidney disease (ESKD) on dialysis were excluded from clinical trials of direct oral anticoagulants for atrial fibrillation (AF). Recent data have raised concerns regarding the safety of dabigatran and rivaroxaban, but apixaban has not been evaluated despite current labeling supporting its use in this population. The goal of this study was to determine patterns of apixaban use and its associated outcomes in dialysis-dependent patients with ESKD and AF.METHODS: We performed a retrospective cohort study of Medicare beneficiaries included in the United States Renal Data System (October 2010 to December 2015). Eligible patients were those with ESKD and AF undergoing dialysis who initiated treatment with an oral anticoagulant. Because of the small number of dabigatran and rivaroxaban users, outcomes were only assessed in patients treated with apixaban or warfarin. Apixaban and warfarin patients were matched (1:3) based on prognostic score. Differences between groups in survival free of stroke or systemic embolism, major bleeding, gastrointestinal bleeding, intracranial bleeding, and death were assessed using Kaplan-Meier analyses. Hazard ratios (HRs) and 95% CIs were derived from Cox regression analyses.RESULTS: The study population consisted of 25 523 patients (45.7% women; 68.2±11.9 years of age), including 2351 patients on apixaban and 23 172 patients on warfarin. An annual increase in apixaban prescriptions was observed after its marketing approval at the end of 2012, such that 26.6% of new anticoagulant prescriptions in 2015 were for apixaban. In matched cohorts, there was no difference in the risks of stroke/systemic embolism between apixaban and warfarin (HR, 0.88; 95% CI, 0.69-1.12; P=0.29), but apixaban was associated with a significantly lower risk of major bleeding (HR, 0.72; 95% CI, 0.59-0.87; P<0.001). In sensitivity analyses, standard-dose apixaban (5 mg twice a day; n=1034) was associated with significantly lower risks of stroke/systemic embolism and death as compared with either reduced-dose apixaban (2.5 mg twice a day; n=1317; HR, 0.61; 95% CI, 0.37-0.98; P=0.04 for stroke/systemic embolism; HR, 0.64; 95% CI, 0.45-0.92; P=0.01 for death) or warfarin (HR, 0.64; 95% CI, 0.42-0.97; P=0.04 for stroke/systemic embolism; HR, 0.63; 95% CI, 0.46-0.85; P=0.003 for death).CONCLUSIONS: Among patients with ESKD and AF on dialysis, apixaban use may be associated with a lower risk of major bleeding compared with warfarin, with a standard 5 mg twice a day dose also associated with reductions in thromboembolic and mortality risk.

KW - anticoagulation

KW - atrial fibrillation

KW - bleeding

KW - dialysis

KW - stroke prevention

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