Impact of renal function on outcomes with edoxaban in real-world patients with atrial fibrillation a nationwide cohort study

Hee Tae Yu, Pil Sung Yang, Tae Hoon Kim, Eunsun Jang, Daehoon Kim, Jae Sun Uhm, Jong Youn Kim, Hui Nam Pak, Moon Hyoung Lee, Gregory Y.H. Lip, Boyoung Joung

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background and Purpose-Edoxaban is a direct oral factor Xa inhibitor with proven efficacy and safety among patients with atrial fibrillation. Concerns have been raised about an excess of stroke among patients with creatinine clearance (CrCl) >95 mg/mL treated with edoxaban. We assessed the real-world effectiveness and safety of edoxaban in atrial fibrillation patients in relation to CrCl. Methods-In the Korean National Health Insurance Service data during the period from January to December 2016, we identified 9537 edoxaban-treated patients. Effectiveness and safety outcomes were compared between high-dose edoxaban regimen (HDER, 60 mg daily, n=2840) and a propensity score-matched warfarin group (n=2840) and between low-dose edoxaban regimen (LDER, 30 mg daily, n=3016) and matched warfarin group (n=3016). Results-The median follow-up period was 5.0 months (interquartile range, 2-7 months). The mean age was 68 years, and 63% were men in HDER group, and the mean age was 73 years, and 52% were men in LDER group. Compared with warfarin, both HDER and LDER significantly decreased the risk for ischemic stroke or systemic embolism (S/SE; HDER: adjusted hazard ratio [aHR], 0.44; 95% CI, 0.31-0.64; LDER: aHR, 0.57; 95% CI, 0.42-0.78), major bleeding (HDER: aHR, 0.40; 95% CI, 0.26-0.61; LDER: aHR, 0.61; 95% CI, 0.43-0.85), and mortality (HDER: aHR, 0.34; 95% CI, 0.22-0.53; LDER: aHR, 0.55; 95% CI, 0.41-0.73). In patients with CrCl >95 mL/min, the incidence of S/SE was higher with LDER than warfarin and comparable between HDER and warfarin group. There was lower effectiveness for the prevention of S/SE with LDER compared with warfarin at higher CrCl levels (P for interaction=0.023). Conclusions-In real-world practice, both doses of edoxaban were associated with reduced risks for S/SE, major bleeding, and mortality compared with warfarin. LDER had lower effectiveness for the prevention of S/SE compared with warfarin at higher levels of CrCl (>95 mL/min).

Original languageEnglish
Pages (from-to)2421-2429
Number of pages9
JournalStroke
Volume49
Issue number10
DOIs
Publication statusPublished - 2018 Jan 1

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Warfarin
Atrial Fibrillation
Cohort Studies
Kidney
Creatinine
National Health Programs
Research Design
Stroke
Hemorrhage
Safety
Propensity Score
Mortality
edoxaban
Patient Safety
Embolism
Age Groups
Incidence

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

Cite this

Yu, Hee Tae ; Yang, Pil Sung ; Kim, Tae Hoon ; Jang, Eunsun ; Kim, Daehoon ; Uhm, Jae Sun ; Kim, Jong Youn ; Pak, Hui Nam ; Lee, Moon Hyoung ; Lip, Gregory Y.H. ; Joung, Boyoung. / Impact of renal function on outcomes with edoxaban in real-world patients with atrial fibrillation a nationwide cohort study. In: Stroke. 2018 ; Vol. 49, No. 10. pp. 2421-2429.
@article{52776f06c55d4163bcd3a231f84de4f9,
title = "Impact of renal function on outcomes with edoxaban in real-world patients with atrial fibrillation a nationwide cohort study",
abstract = "Background and Purpose-Edoxaban is a direct oral factor Xa inhibitor with proven efficacy and safety among patients with atrial fibrillation. Concerns have been raised about an excess of stroke among patients with creatinine clearance (CrCl) >95 mg/mL treated with edoxaban. We assessed the real-world effectiveness and safety of edoxaban in atrial fibrillation patients in relation to CrCl. Methods-In the Korean National Health Insurance Service data during the period from January to December 2016, we identified 9537 edoxaban-treated patients. Effectiveness and safety outcomes were compared between high-dose edoxaban regimen (HDER, 60 mg daily, n=2840) and a propensity score-matched warfarin group (n=2840) and between low-dose edoxaban regimen (LDER, 30 mg daily, n=3016) and matched warfarin group (n=3016). Results-The median follow-up period was 5.0 months (interquartile range, 2-7 months). The mean age was 68 years, and 63{\%} were men in HDER group, and the mean age was 73 years, and 52{\%} were men in LDER group. Compared with warfarin, both HDER and LDER significantly decreased the risk for ischemic stroke or systemic embolism (S/SE; HDER: adjusted hazard ratio [aHR], 0.44; 95{\%} CI, 0.31-0.64; LDER: aHR, 0.57; 95{\%} CI, 0.42-0.78), major bleeding (HDER: aHR, 0.40; 95{\%} CI, 0.26-0.61; LDER: aHR, 0.61; 95{\%} CI, 0.43-0.85), and mortality (HDER: aHR, 0.34; 95{\%} CI, 0.22-0.53; LDER: aHR, 0.55; 95{\%} CI, 0.41-0.73). In patients with CrCl >95 mL/min, the incidence of S/SE was higher with LDER than warfarin and comparable between HDER and warfarin group. There was lower effectiveness for the prevention of S/SE with LDER compared with warfarin at higher CrCl levels (P for interaction=0.023). Conclusions-In real-world practice, both doses of edoxaban were associated with reduced risks for S/SE, major bleeding, and mortality compared with warfarin. LDER had lower effectiveness for the prevention of S/SE compared with warfarin at higher levels of CrCl (>95 mL/min).",
author = "Yu, {Hee Tae} and Yang, {Pil Sung} and Kim, {Tae Hoon} and Eunsun Jang and Daehoon Kim and Uhm, {Jae Sun} and Kim, {Jong Youn} and Pak, {Hui Nam} and Lee, {Moon Hyoung} and Lip, {Gregory Y.H.} and Boyoung Joung",
year = "2018",
month = "1",
day = "1",
doi = "10.1161/STROKEAHA.118.021387",
language = "English",
volume = "49",
pages = "2421--2429",
journal = "Stroke",
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Impact of renal function on outcomes with edoxaban in real-world patients with atrial fibrillation a nationwide cohort study. / Yu, Hee Tae; Yang, Pil Sung; Kim, Tae Hoon; Jang, Eunsun; Kim, Daehoon; Uhm, Jae Sun; Kim, Jong Youn; Pak, Hui Nam; Lee, Moon Hyoung; Lip, Gregory Y.H.; Joung, Boyoung.

In: Stroke, Vol. 49, No. 10, 01.01.2018, p. 2421-2429.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Impact of renal function on outcomes with edoxaban in real-world patients with atrial fibrillation a nationwide cohort study

AU - Yu, Hee Tae

AU - Yang, Pil Sung

AU - Kim, Tae Hoon

AU - Jang, Eunsun

AU - Kim, Daehoon

AU - Uhm, Jae Sun

AU - Kim, Jong Youn

AU - Pak, Hui Nam

AU - Lee, Moon Hyoung

AU - Lip, Gregory Y.H.

AU - Joung, Boyoung

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background and Purpose-Edoxaban is a direct oral factor Xa inhibitor with proven efficacy and safety among patients with atrial fibrillation. Concerns have been raised about an excess of stroke among patients with creatinine clearance (CrCl) >95 mg/mL treated with edoxaban. We assessed the real-world effectiveness and safety of edoxaban in atrial fibrillation patients in relation to CrCl. Methods-In the Korean National Health Insurance Service data during the period from January to December 2016, we identified 9537 edoxaban-treated patients. Effectiveness and safety outcomes were compared between high-dose edoxaban regimen (HDER, 60 mg daily, n=2840) and a propensity score-matched warfarin group (n=2840) and between low-dose edoxaban regimen (LDER, 30 mg daily, n=3016) and matched warfarin group (n=3016). Results-The median follow-up period was 5.0 months (interquartile range, 2-7 months). The mean age was 68 years, and 63% were men in HDER group, and the mean age was 73 years, and 52% were men in LDER group. Compared with warfarin, both HDER and LDER significantly decreased the risk for ischemic stroke or systemic embolism (S/SE; HDER: adjusted hazard ratio [aHR], 0.44; 95% CI, 0.31-0.64; LDER: aHR, 0.57; 95% CI, 0.42-0.78), major bleeding (HDER: aHR, 0.40; 95% CI, 0.26-0.61; LDER: aHR, 0.61; 95% CI, 0.43-0.85), and mortality (HDER: aHR, 0.34; 95% CI, 0.22-0.53; LDER: aHR, 0.55; 95% CI, 0.41-0.73). In patients with CrCl >95 mL/min, the incidence of S/SE was higher with LDER than warfarin and comparable between HDER and warfarin group. There was lower effectiveness for the prevention of S/SE with LDER compared with warfarin at higher CrCl levels (P for interaction=0.023). Conclusions-In real-world practice, both doses of edoxaban were associated with reduced risks for S/SE, major bleeding, and mortality compared with warfarin. LDER had lower effectiveness for the prevention of S/SE compared with warfarin at higher levels of CrCl (>95 mL/min).

AB - Background and Purpose-Edoxaban is a direct oral factor Xa inhibitor with proven efficacy and safety among patients with atrial fibrillation. Concerns have been raised about an excess of stroke among patients with creatinine clearance (CrCl) >95 mg/mL treated with edoxaban. We assessed the real-world effectiveness and safety of edoxaban in atrial fibrillation patients in relation to CrCl. Methods-In the Korean National Health Insurance Service data during the period from January to December 2016, we identified 9537 edoxaban-treated patients. Effectiveness and safety outcomes were compared between high-dose edoxaban regimen (HDER, 60 mg daily, n=2840) and a propensity score-matched warfarin group (n=2840) and between low-dose edoxaban regimen (LDER, 30 mg daily, n=3016) and matched warfarin group (n=3016). Results-The median follow-up period was 5.0 months (interquartile range, 2-7 months). The mean age was 68 years, and 63% were men in HDER group, and the mean age was 73 years, and 52% were men in LDER group. Compared with warfarin, both HDER and LDER significantly decreased the risk for ischemic stroke or systemic embolism (S/SE; HDER: adjusted hazard ratio [aHR], 0.44; 95% CI, 0.31-0.64; LDER: aHR, 0.57; 95% CI, 0.42-0.78), major bleeding (HDER: aHR, 0.40; 95% CI, 0.26-0.61; LDER: aHR, 0.61; 95% CI, 0.43-0.85), and mortality (HDER: aHR, 0.34; 95% CI, 0.22-0.53; LDER: aHR, 0.55; 95% CI, 0.41-0.73). In patients with CrCl >95 mL/min, the incidence of S/SE was higher with LDER than warfarin and comparable between HDER and warfarin group. There was lower effectiveness for the prevention of S/SE with LDER compared with warfarin at higher CrCl levels (P for interaction=0.023). Conclusions-In real-world practice, both doses of edoxaban were associated with reduced risks for S/SE, major bleeding, and mortality compared with warfarin. LDER had lower effectiveness for the prevention of S/SE compared with warfarin at higher levels of CrCl (>95 mL/min).

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