Rivaroxaban was found to be noninferior to warfarin in routine clinical care: A retrospective noninferiority cohort replication study

Turki A Althunian; Anthonius de Boer; Rolf H H Groenwold; Katrien O Rengerink; Patrick C Souverein; Olaf H Klungel

doi:10.1002/pds.5065

Rivaroxaban was found to be noninferior to warfarin in routine clinical care: A retrospective noninferiority cohort replication study

Turki A Althunian, Anthonius de Boer, Rolf H H Groenwold, Katrien O Rengerink, Patrick C Souverein, Olaf H Klungel

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Abstract

PURPOSE: To compare the effectiveness and safety of a drug in daily practice with the outcomes of a target non-inferiority trial by rigorously mimickingin an observational study the trial's design features.

METHODS: This cohort study was conducted using the British Clinical Practice Research Datalink (CPRD) to emulate the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial. Patients with atrial fibrillation who were newly prescribed (>=12 months of no use) either rivaroxaban or warfarinfrom October 2008 to December 2017 were included. Non-inferiority of rivaroxaban to warfarin in the prevention of stroke or systemic embolism was assessed in different analysis populations (intention-to-treat [ITT], per-protocol [PP], and as-treated populations) using a hazardratio (HR) of 1.46 as the non-inferiority margin. Major bleeding (safety outcome) was also assessed and compared to that of the target trial. All outcomes were analyzed using Cox-proportional hazard analyses.

RESULTS: We included 25,473 incident users of rivaroxaban (n=4,008) or warfarin(n=21,465). Similar to the trial, non-inferiority in the primary out come was demonstrated in all three analysis populations: HR=1.04 (95%CI 0.84 to 1.30) (ITT), HR=0.98 (95%CI 0.70 to 1.38) (PP), and HR=1.11 (95%CI 0.86 to 1.42) (as-treated). Risk of major bleeding was also similar to the target trial.

CONCLUSION: The results of this study provide supportive evidence to the effectiveness of rivaroxaban and adds knowledge on the usefulness of emulating a non-inferiority trial to assess drug effectiveness.

Original language	English
Pages (from-to)	1263-1272
Number of pages	10
Journal	Pharmacoepidemiology and Drug Safety
Volume	29
Issue number	10
Early online date	14 Jun 2020
DOIs	https://doi.org/10.1002/pds.5065
Publication status	Published - Oct 2020

Keywords

effectivness
electronic health care records
noninferiority
observational studies
pharmacoepidemiology
real-world evidence, methodology
real-world evidence
methodology

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@article{1854b2107e1d4833ae6eec909be23333,

title = "Rivaroxaban was found to be noninferior to warfarin in routine clinical care: A retrospective noninferiority cohort replication study",

abstract = "PURPOSE: To compare the effectiveness and safety of a drug in daily practice with the outcomes of a target non-inferiority trial by rigorously mimickingin an observational study the trial's design features.METHODS: This cohort study was conducted using the British Clinical Practice Research Datalink (CPRD) to emulate the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial. Patients with atrial fibrillation who were newly prescribed (>=12 months of no use) either rivaroxaban or warfarinfrom October 2008 to December 2017 were included. Non-inferiority of rivaroxaban to warfarin in the prevention of stroke or systemic embolism was assessed in different analysis populations (intention-to-treat [ITT], per-protocol [PP], and as-treated populations) using a hazardratio (HR) of 1.46 as the non-inferiority margin. Major bleeding (safety outcome) was also assessed and compared to that of the target trial. All outcomes were analyzed using Cox-proportional hazard analyses.RESULTS: We included 25,473 incident users of rivaroxaban (n=4,008) or warfarin(n=21,465). Similar to the trial, non-inferiority in the primary out come was demonstrated in all three analysis populations: HR=1.04 (95\%CI 0.84 to 1.30) (ITT), HR=0.98 (95\%CI 0.70 to 1.38) (PP), and HR=1.11 (95\%CI 0.86 to 1.42) (as-treated). Risk of major bleeding was also similar to the target trial.CONCLUSION: The results of this study provide supportive evidence to the effectiveness of rivaroxaban and adds knowledge on the usefulness of emulating a non-inferiority trial to assess drug effectiveness.",

keywords = "effectivness, electronic health care records, noninferiority, observational studies, pharmacoepidemiology, real-world evidence, methodology, real-world evidence, methodology",

author = "Althunian, \{Turki A\} and \{de Boer\}, Anthonius and Groenwold, \{Rolf H H\} and Rengerink, \{Katrien O\} and Souverein, \{Patrick C\} and Klungel, \{Olaf H\}",

note = "Funding Information: This work was supported by the Saudi Food and Drug Authority (SFDA) as a part of a Doctor of Philosophy (PhD) project for Mr Althunian. The SFDA has no role in any aspect of the study. Additionally, the SFDA has no role in the preparation, review, or the approval of the manuscript, and has no role in the publication of the manuscript. Publisher Copyright: {\textcopyright} 2020 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley \& Sons Ltd. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

month = oct,

doi = "10.1002/pds.5065",

language = "English",

volume = "29",

pages = "1263--1272",

journal = "Pharmacoepidemiology and Drug Safety",

issn = "1053-8569",

publisher = "John Wiley \& Sons Inc.",

number = "10",

}

TY - JOUR

T1 - Rivaroxaban was found to be noninferior to warfarin in routine clinical care

T2 - A retrospective noninferiority cohort replication study

AU - Althunian, Turki A

AU - de Boer, Anthonius

AU - Groenwold, Rolf H H

AU - Rengerink, Katrien O

AU - Souverein, Patrick C

AU - Klungel, Olaf H

N1 - Funding Information: This work was supported by the Saudi Food and Drug Authority (SFDA) as a part of a Doctor of Philosophy (PhD) project for Mr Althunian. The SFDA has no role in any aspect of the study. Additionally, the SFDA has no role in the preparation, review, or the approval of the manuscript, and has no role in the publication of the manuscript. Publisher Copyright: © 2020 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/10

Y1 - 2020/10

N2 - PURPOSE: To compare the effectiveness and safety of a drug in daily practice with the outcomes of a target non-inferiority trial by rigorously mimickingin an observational study the trial's design features.METHODS: This cohort study was conducted using the British Clinical Practice Research Datalink (CPRD) to emulate the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial. Patients with atrial fibrillation who were newly prescribed (>=12 months of no use) either rivaroxaban or warfarinfrom October 2008 to December 2017 were included. Non-inferiority of rivaroxaban to warfarin in the prevention of stroke or systemic embolism was assessed in different analysis populations (intention-to-treat [ITT], per-protocol [PP], and as-treated populations) using a hazardratio (HR) of 1.46 as the non-inferiority margin. Major bleeding (safety outcome) was also assessed and compared to that of the target trial. All outcomes were analyzed using Cox-proportional hazard analyses.RESULTS: We included 25,473 incident users of rivaroxaban (n=4,008) or warfarin(n=21,465). Similar to the trial, non-inferiority in the primary out come was demonstrated in all three analysis populations: HR=1.04 (95%CI 0.84 to 1.30) (ITT), HR=0.98 (95%CI 0.70 to 1.38) (PP), and HR=1.11 (95%CI 0.86 to 1.42) (as-treated). Risk of major bleeding was also similar to the target trial.CONCLUSION: The results of this study provide supportive evidence to the effectiveness of rivaroxaban and adds knowledge on the usefulness of emulating a non-inferiority trial to assess drug effectiveness.

AB - PURPOSE: To compare the effectiveness and safety of a drug in daily practice with the outcomes of a target non-inferiority trial by rigorously mimickingin an observational study the trial's design features.METHODS: This cohort study was conducted using the British Clinical Practice Research Datalink (CPRD) to emulate the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial. Patients with atrial fibrillation who were newly prescribed (>=12 months of no use) either rivaroxaban or warfarinfrom October 2008 to December 2017 were included. Non-inferiority of rivaroxaban to warfarin in the prevention of stroke or systemic embolism was assessed in different analysis populations (intention-to-treat [ITT], per-protocol [PP], and as-treated populations) using a hazardratio (HR) of 1.46 as the non-inferiority margin. Major bleeding (safety outcome) was also assessed and compared to that of the target trial. All outcomes were analyzed using Cox-proportional hazard analyses.RESULTS: We included 25,473 incident users of rivaroxaban (n=4,008) or warfarin(n=21,465). Similar to the trial, non-inferiority in the primary out come was demonstrated in all three analysis populations: HR=1.04 (95%CI 0.84 to 1.30) (ITT), HR=0.98 (95%CI 0.70 to 1.38) (PP), and HR=1.11 (95%CI 0.86 to 1.42) (as-treated). Risk of major bleeding was also similar to the target trial.CONCLUSION: The results of this study provide supportive evidence to the effectiveness of rivaroxaban and adds knowledge on the usefulness of emulating a non-inferiority trial to assess drug effectiveness.

KW - effectivness

KW - electronic health care records

KW - noninferiority

KW - observational studies

KW - pharmacoepidemiology

KW - real-world evidence, methodology

KW - real-world evidence

KW - methodology

UR - https://www.scopus.com/pages/publications/85086411886

U2 - 10.1002/pds.5065

DO - 10.1002/pds.5065

M3 - Article

C2 - 32537897

SN - 1053-8569

VL - 29

SP - 1263

EP - 1272

JO - Pharmacoepidemiology and Drug Safety

JF - Pharmacoepidemiology and Drug Safety

IS - 10

ER -

Rivaroxaban was found to be noninferior to warfarin in routine clinical care: A retrospective noninferiority cohort replication study

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