search
Back to results

Effects of APIXaban on BRAIN Protection in Patients With Sinus Rhythm and Heart Failure: APIXBRAIN-HF Trial

Primary Purpose

Heart Failure, Sinus Rhythm, Cerebrovascular Disease

Status
Unknown status
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Apixaban
Placebo
Sponsored by
Korea University Guro Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure focused on measuring Heart failure, Sinus rhythm, NOAC, Brain

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients aged over 19 years old
  • Patients with sinus rhythm

  • Newly diagnosed of heart failure or aggravated heart failure symptom

    1. Dyspnea (≥ NYHA II)
    2. plasma BNP ≥ 200 pg/ml or NT-proBNP ≥ 800 pg/ml

  • LV systolic dysfunction on echocardiography within 3 month of enrollment

    1) LVEF ≤ 40%

  • Those with CHA2DS2-VASc ≥ 3
  • Modified Rankin Score ≤ 4

Exclusion Criteria:

  • Patients already subscribed warfarin or antiplatelet therapy or have clear indication for warfarin or antiplatelet therapy
  • At high risk for bleeding
  • Patients with atrial fibrillation
  • Estimated glomerular filtration rate (CKD-EPI formula) < 15 ml/min/1.73 m2)
  • Recent stroke or brain hemorrhage (within 3 months)
  • Patients who was diagnosed of myocardial infarction or who has plan to PCI/CABG at enrollment
  • End stage heart failure with life expectancy ≤ 6 months
  • Patients with bed ridden status (Modified Rankin Score ≥ 5)
  • Patients with liver dysfunction (AST, ALT > 2 times of upper normal limits or total bilirubin > 1.5 of upper normal limits)
  • At of pregnancy or breastfeeding
  • Patients who disagree with the use of medically acceptable contraception during the clinical trial period
  • Patients with contraindication of apixaban

Sites / Locations

  • Korea University Guro Hospital
  • Korea University Ansan Hospital
  • Chungnam National University Hospital
  • Hallym University Dongtan Sacred Heart Hospital
  • Seoul National University Bundang Hospital
  • Korea University Anam Hospital
  • Severance Hospital
  • Asan Medical Center
  • Samsung Medical Center
  • Wonju Severance Christian Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Study group: apixaban

Control group: placebo

Arm Description

apixaban 2.5mg or 5mg bid

placebo bid

Outcomes

Primary Outcome Measures

New occurrence of brain pathology
1) Cortical cerebral microinfarcts 2) Silent lacunar infarction 3)Progression of white matter hyperintensities

Secondary Outcome Measures

The change of Mini-Mental State Examination-2 (MMSE-2) score
The change of Mini-Mental State Examination-2 (MMSE-2) score compared to baseline. Higher scores mean a better outcome.
New occurrence of cortical cerebral microinfarcts
New occurrence of cortical cerebral microinfarcts compared to baseline
New occurrence of silent lacunar infarction
New occurrence of silent lacunar infarction compared to baseline
Progression of white matter hyperintensities (more than 10% increase)
Progression of white matter hyperintensities (more than 10% increase) compared to baseline

Full Information

First Posted
January 3, 2021
Last Updated
January 15, 2021
Sponsor
Korea University Guro Hospital
Collaborators
Dt&Sanomedics
search

1. Study Identification

Unique Protocol Identification Number
NCT04696120
Brief Title
Effects of APIXaban on BRAIN Protection in Patients With Sinus Rhythm and Heart Failure: APIXBRAIN-HF Trial
Official Title
Effects of APIXaban on BRAIN Protection in Patients With Sinus Rhythm and Heart Failure: APIXBRAIN-HF Trial
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Unknown status
Study Start Date
March 2, 2021 (Anticipated)
Primary Completion Date
August 30, 2022 (Anticipated)
Study Completion Date
February 28, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Korea University Guro Hospital
Collaborators
Dt&Sanomedics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
objectives: The primary aim of APIXBRAIN-HF Trial is to explore the effects of apixaban on brain protection in patients with sinus rhythm and heart failure Primary / Secondary Endpoint New occurrence of brain pathology 1) Cortical cerebral microinfarcts 2) Silent lacunar infarction 3)Progression of white matter hyperintensities Secondary endpoint 1) The change of cognitive function evaluated by MMSE-2 2) Individual variable of primary endpoint Safety Endpoint Evaluation 1) Cerebral microbleeds on imaging
Detailed Description
This study is a double-blind, parallel-group, and randomization study. The investigators will enroll the patients with heart failure who demonstrated LV systolic dysfunction (LVEF ≤ 40%) and sinus rhythm with a CHA2DS2-VASc score ≥ 3. All patients would be randomly assigned to either the apixaban group or placebo group. Patients assigned to the apixaban group will receive 5mg bid or 2.5mg bid (patients with at least 2 of the following characteristics: aged≥80-year, bodyweight ≤60kg, serum creatinine 1.5 ml/dL) and patients in the placebo group will receive a placebo of apixaban. Both drugs will be maintained for 6 months. During the study period, all patients will be carefully monitored for thromboembolic events, including stroke. At the beginning of the study and 6 months after randomization, 3T Brain MRI and MMSE-2 test will be performed to identify changes in brain structure and cognitive function.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Sinus Rhythm, Cerebrovascular Disease
Keywords
Heart failure, Sinus rhythm, NOAC, Brain

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Study group: apixaban
Arm Type
Experimental
Arm Description
apixaban 2.5mg or 5mg bid
Arm Title
Control group: placebo
Arm Type
Placebo Comparator
Arm Description
placebo bid
Intervention Type
Drug
Intervention Name(s)
Apixaban
Other Intervention Name(s)
apixaban 5mg or 2.5mg bid
Intervention Description
Patients who are randomly assigned to apixaban group will receive apixaban 5mg or 2.5mg bid
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
placebo bid
Intervention Description
All patients who are assigned to placebo group will receive placebo
Primary Outcome Measure Information:
Title
New occurrence of brain pathology
Description
1) Cortical cerebral microinfarcts 2) Silent lacunar infarction 3)Progression of white matter hyperintensities
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
The change of Mini-Mental State Examination-2 (MMSE-2) score
Description
The change of Mini-Mental State Examination-2 (MMSE-2) score compared to baseline. Higher scores mean a better outcome.
Time Frame
24 weeks
Title
New occurrence of cortical cerebral microinfarcts
Description
New occurrence of cortical cerebral microinfarcts compared to baseline
Time Frame
24 weeks
Title
New occurrence of silent lacunar infarction
Description
New occurrence of silent lacunar infarction compared to baseline
Time Frame
24 weeks
Title
Progression of white matter hyperintensities (more than 10% increase)
Description
Progression of white matter hyperintensities (more than 10% increase) compared to baseline
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients aged over 19 years old Patients with sinus rhythm Newly diagnosed of heart failure or aggravated heart failure symptom Dyspnea (≥ NYHA II) plasma BNP ≥ 200 pg/ml or NT-proBNP ≥ 800 pg/ml LV systolic dysfunction on echocardiography within 3 month of enrollment 1) LVEF ≤ 40% Those with CHA2DS2-VASc ≥ 3 Modified Rankin Score ≤ 4 Exclusion Criteria: Patients already subscribed warfarin or antiplatelet therapy or have clear indication for warfarin or antiplatelet therapy At high risk for bleeding Patients with atrial fibrillation Estimated glomerular filtration rate (CKD-EPI formula) < 15 ml/min/1.73 m2) Recent stroke or brain hemorrhage (within 3 months) Patients who was diagnosed of myocardial infarction or who has plan to PCI/CABG at enrollment End stage heart failure with life expectancy ≤ 6 months Patients with bed ridden status (Modified Rankin Score ≥ 5) Patients with liver dysfunction (AST, ALT > 2 times of upper normal limits or total bilirubin > 1.5 of upper normal limits) At of pregnancy or breastfeeding Patients who disagree with the use of medically acceptable contraception during the clinical trial period Patients with contraindication of apixaban
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eung Ju Kim, MD, PhD
Phone
82-02-2626-3022
Email
withnoel@empas.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jah Yeon Choi, MD, PhD
Email
kekeruki@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eung Ju Kim, MD, PhD.
Organizational Affiliation
Professor
Official's Role
Principal Investigator
Facility Information:
Facility Name
Korea University Guro Hospital
City
Seoul
State/Province
Guro-gu
ZIP/Postal Code
08308
Country
Korea, Republic of
Facility Name
Korea University Ansan Hospital
City
Ansan
ZIP/Postal Code
15355
Country
Korea, Republic of
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sung Hwan Kim, MD,PhD.
Email
echoshkim@gmail.com
Facility Name
Chungnam National University Hospital
City
Daejeon
ZIP/Postal Code
35015
Country
Korea, Republic of
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jin Ok Cheong, MD,PhD.
Email
jojeong@cnu.ac.kr
Facility Name
Hallym University Dongtan Sacred Heart Hospital
City
Hwaseong-si
ZIP/Postal Code
18450
Country
Korea, Republic of
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Seong Woo Han, MD,PhD.
Email
hansw29@hanmail.net
Facility Name
Seoul National University Bundang Hospital
City
Seongnam-si
ZIP/Postal Code
13620
Country
Korea, Republic of
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dong ju Choi, MD,PhD.
Email
djchoi@snubh.org
First Name & Middle Initial & Last Name & Degree
Jin Joo Park, MD,PhD.
Email
65755@snubh.org
Facility Name
Korea University Anam Hospital
City
Seoul
ZIP/Postal Code
02841
Country
Korea, Republic of
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sung Mi Park, MD,PhD.
Email
smparkmd@korea.ac.kr
First Name & Middle Initial & Last Name & Degree
Mi-Na Kim, MD,PhD.
Email
alsk1229@gmail.com
Facility Name
Severance Hospital
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Seok Min Kang, MD,PhD.
Email
SMKANG@yuhs.ac
First Name & Middle Initial & Last Name & Degree
Jaewon Oh, MD,PhD.
Email
ericjcoh@yuhs.ac
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Min Seok Kim, MD,PhD.
Email
guess124@gmail.com
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jin Oh Choi, MD,PhD.
Email
choijean5@gmail.com
Facility Name
Wonju Severance Christian Hospital
City
Wonju
ZIP/Postal Code
26426
Country
Korea, Republic of
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Byeong Soo Yoo, MD,PhD.
Email
yubs@yonsei.ac.kr

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28834669
Citation
Ponikowski P, Anker SD, AlHabib KF, Cowie MR, Force TL, Hu S, Jaarsma T, Krum H, Rastogi V, Rohde LE, Samal UC, Shimokawa H, Budi Siswanto B, Sliwa K, Filippatos G. Heart failure: preventing disease and death worldwide. ESC Heart Fail. 2014 Sep;1(1):4-25. doi: 10.1002/ehf2.12005.
Results Reference
background
PubMed Identifier
27733282
Citation
GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016 Oct 8;388(10053):1545-1602. doi: 10.1016/S0140-6736(16)31678-6. Erratum In: Lancet. 2017 Jan 7;389(10064):e1.
Results Reference
background
PubMed Identifier
26673558
Citation
Writing Group Members; Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Isasi CR, Jimenez MC, Judd SE, Kissela BM, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Magid DJ, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Rosamond W, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Woo D, Yeh RW, Turner MB; American Heart Association Statistics Committee; Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. 2016 Jan 26;133(4):e38-360. doi: 10.1161/CIR.0000000000000350. Epub 2015 Dec 16. No abstract available. Erratum In: Circulation. 2016 Apr 12;133(15):e599.
Results Reference
background
PubMed Identifier
21262990
Citation
Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz MD, Finkelstein EA, Hong Y, Johnston SC, Khera A, Lloyd-Jones DM, Nelson SA, Nichol G, Orenstein D, Wilson PW, Woo YJ; American Heart Association Advocacy Coordinating Committee; Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Clinical Cardiology; Council on Epidemiology and Prevention; Council on Arteriosclerosis; Thrombosis and Vascular Biology; Council on Cardiopulmonary; Critical Care; Perioperative and Resuscitation; Council on Cardiovascular Nursing; Council on the Kidney in Cardiovascular Disease; Council on Cardiovascular Surgery and Anesthesia, and Interdisciplinary Council on Quality of Care and Outcomes Research. Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation. 2011 Mar 1;123(8):933-44. doi: 10.1161/CIR.0b013e31820a55f5. Epub 2011 Jan 24.
Results Reference
background
PubMed Identifier
26235928
Citation
Nichols GA, Reynolds K, Kimes TM, Rosales AG, Chan WW. Comparison of Risk of Re-hospitalization, All-Cause Mortality, and Medical Care Resource Utilization in Patients With Heart Failure and Preserved Versus Reduced Ejection Fraction. Am J Cardiol. 2015 Oct 1;116(7):1088-92. doi: 10.1016/j.amjcard.2015.07.018. Epub 2015 Jul 15.
Results Reference
background
PubMed Identifier
23537547
Citation
Maggioni AP, Dahlstrom U, Filippatos G, Chioncel O, Crespo Leiro M, Drozdz J, Fruhwald F, Gullestad L, Logeart D, Fabbri G, Urso R, Metra M, Parissis J, Persson H, Ponikowski P, Rauchhaus M, Voors AA, Nielsen OW, Zannad F, Tavazzi L; Heart Failure Association of the European Society of Cardiology (HFA). EURObservational Research Programme: regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart Fail. 2013 Jul;15(7):808-17. doi: 10.1093/eurjhf/hft050. Epub 2013 Mar 28.
Results Reference
background
PubMed Identifier
26935038
Citation
Ziaeian B, Fonarow GC. Epidemiology and aetiology of heart failure. Nat Rev Cardiol. 2016 Jun;13(6):368-78. doi: 10.1038/nrcardio.2016.25. Epub 2016 Mar 3.
Results Reference
background
PubMed Identifier
28470962
Citation
Mamas MA, Sperrin M, Watson MC, Coutts A, Wilde K, Burton C, Kadam UT, Kwok CS, Clark AB, Murchie P, Buchan I, Hannaford PC, Myint PK. Do patients have worse outcomes in heart failure than in cancer? A primary care-based cohort study with 10-year follow-up in Scotland. Eur J Heart Fail. 2017 Sep;19(9):1095-1104. doi: 10.1002/ejhf.822. Epub 2017 May 3.
Results Reference
background
PubMed Identifier
29402070
Citation
Kim W, Kim EJ. Heart Failure as a Risk Factor for Stroke. J Stroke. 2018 Jan;20(1):33-45. doi: 10.5853/jos.2017.02810. Epub 2018 Jan 31.
Results Reference
background
PubMed Identifier
19181288
Citation
Divani AA, Vazquez G, Asadollahi M, Qureshi AI, Pullicino P. Nationwide frequency and association of heart failure on stroke outcomes in the United States. J Card Fail. 2009 Feb;15(1):11-6. doi: 10.1016/j.cardfail.2008.09.001. Epub 2008 Dec 25.
Results Reference
background
PubMed Identifier
16741172
Citation
Hays AG, Sacco RL, Rundek T, Sciacca RR, Jin Z, Liu R, Homma S, Di Tullio MR. Left ventricular systolic dysfunction and the risk of ischemic stroke in a multiethnic population. Stroke. 2006 Jul;37(7):1715-9. doi: 10.1161/01.STR.0000227121.34717.40. Epub 2006 Jun 1.
Results Reference
background
PubMed Identifier
20123219
Citation
Pullicino P, Homma S. Stroke in heart failure: atrial fibrillation revisited? J Stroke Cerebrovasc Dis. 2010 Jan;19(1):1-2. doi: 10.1016/j.jstrokecerebrovasdis.2009.09.002. No abstract available.
Results Reference
background
PubMed Identifier
21903953
Citation
Haeusler KG, Laufs U, Endres M. Chronic heart failure and ischemic stroke. Stroke. 2011 Oct;42(10):2977-82. doi: 10.1161/STROKEAHA.111.628479. Epub 2011 Sep 8.
Results Reference
background
PubMed Identifier
28377383
Citation
Adelborg K, Szepligeti S, Sundboll J, Horvath-Puho E, Henderson VW, Ording A, Pedersen L, Sorensen HT. Risk of Stroke in Patients With Heart Failure: A Population-Based 30-Year Cohort Study. Stroke. 2017 May;48(5):1161-1168. doi: 10.1161/STROKEAHA.116.016022. Epub 2017 Apr 4.
Results Reference
background
PubMed Identifier
28826798
Citation
Kang SH, Kim J, Park JJ, Oh IY, Yoon CH, Kim HJ, Kim K, Choi DJ. Risk of stroke in congestive heart failure with and without atrial fibrillation. Int J Cardiol. 2017 Dec 1;248:182-187. doi: 10.1016/j.ijcard.2017.07.056. Epub 2017 Jul 20.
Results Reference
background
PubMed Identifier
28426886
Citation
Abdul-Rahim AH, Perez AC, MacIsaac RL, Jhund PS, Claggett BL, Carson PE, Komajda M, McKelvie RS, Zile MR, Swedberg K, Yusuf S, Pfeffer MA, Solomon SD, Lip GYH, Lees KR, McMurray JJV; Candesartan in Heart failure Assessment of Reduction in Mortality and Morbidity-Preserved (CHARM-Preserved) and the Irbesartan in Heart Failure with Preserved Systolic Function (I-Preserve) Steering Committees. Risk of stroke in chronic heart failure patients with preserved ejection fraction, but without atrial fibrillation: analysis of the CHARM-Preserved and I-Preserve trials. Eur Heart J. 2017 Mar 7;38(10):742-750. doi: 10.1093/eurheartj/ehw509. Erratum In: Eur Heart J. 2018 Apr 21;39(16):1403.
Results Reference
background
PubMed Identifier
25810334
Citation
Abdul-Rahim AH, Perez AC, Fulton RL, Jhund PS, Latini R, Tognoni G, Wikstrand J, Kjekshus J, Lip GY, Maggioni AP, Tavazzi L, Lees KR, McMurray JJ; Investigators of the Controlled Rosuvastatin Multinational Study in Heart Failure (CORONA); GISSI-Heart Failure (GISSI-HF) Committees and Investigators. Risk of Stroke in Chronic Heart Failure Patients Without Atrial Fibrillation: Analysis of the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure (GISSI-HF) Trials. Circulation. 2015 Apr 28;131(17):1486-94; discussion 1494. doi: 10.1161/CIRCULATIONAHA.114.013760. Epub 2015 Mar 25.
Results Reference
background
PubMed Identifier
9489967
Citation
Kalaria VG, Passannante MR, Shah T, Modi K, Weisse AB. Effect of mitral regurgitation on left ventricular thrombus formation in dilated cardiomyopathy. Am Heart J. 1998 Feb;135(2 Pt 1):215-20. doi: 10.1016/s0002-8703(98)70084-5.
Results Reference
background
PubMed Identifier
10193748
Citation
Lip GY, Gibbs CR. Does heart failure confer a hypercoagulable state? Virchow's triad revisited. J Am Coll Cardiol. 1999 Apr;33(5):1424-6. doi: 10.1016/s0735-1097(99)00033-9.
Results Reference
background
PubMed Identifier
17719270
Citation
Vogels RL, van der Flier WM, van Harten B, Gouw AA, Scheltens P, Schroeder-Tanka JM, Weinstein HC. Brain magnetic resonance imaging abnormalities in patients with heart failure. Eur J Heart Fail. 2007 Oct;9(10):1003-9. doi: 10.1016/j.ejheart.2007.07.006. Epub 2007 Aug 23.
Results Reference
background
PubMed Identifier
28335844
Citation
Havakuk O, King KS, Grazette L, Yoon AJ, Fong M, Bregman N, Elkayam U, Kloner RA. Heart Failure-Induced Brain Injury. J Am Coll Cardiol. 2017 Mar 28;69(12):1609-1616. doi: 10.1016/j.jacc.2017.01.022.
Results Reference
background
PubMed Identifier
29885954
Citation
Frey A, Sell R, Homola GA, Malsch C, Kraft P, Gunreben I, Morbach C, Alkonyi B, Schmid E, Colonna I, Hofer E, Mullges W, Ertl G, Heuschmann P, Solymosi L, Schmidt R, Stork S, Stoll G. Cognitive Deficits and Related Brain Lesions in Patients With Chronic Heart Failure. JACC Heart Fail. 2018 Jul;6(7):583-592. doi: 10.1016/j.jchf.2018.03.010. Epub 2018 Jun 6.
Results Reference
background
PubMed Identifier
22551105
Citation
Homma S, Thompson JL, Pullicino PM, Levin B, Freudenberger RS, Teerlink JR, Ammon SE, Graham S, Sacco RL, Mann DL, Mohr JP, Massie BM, Labovitz AJ, Anker SD, Lok DJ, Ponikowski P, Estol CJ, Lip GY, Di Tullio MR, Sanford AR, Mejia V, Gabriel AP, del Valle ML, Buchsbaum R; WARCEF Investigators. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012 May 17;366(20):1859-69. doi: 10.1056/NEJMoa1202299. Epub 2012 May 2.
Results Reference
background
PubMed Identifier
16737850
Citation
Cokkinos DV, Haralabopoulos GC, Kostis JB, Toutouzas PK; HELAS investigators. Efficacy of antithrombotic therapy in chronic heart failure: the HELAS study. Eur J Heart Fail. 2006 Jun;8(4):428-32. doi: 10.1016/j.ejheart.2006.02.012. Epub 2006 Jun 5.
Results Reference
background
PubMed Identifier
15215806
Citation
Cleland JG, Findlay I, Jafri S, Sutton G, Falk R, Bulpitt C, Prentice C, Ford I, Trainer A, Poole-Wilson PA. The Warfarin/Aspirin Study in Heart failure (WASH): a randomized trial comparing antithrombotic strategies for patients with heart failure. Am Heart J. 2004 Jul;148(1):157-64. doi: 10.1016/j.ahj.2004.03.010.
Results Reference
background
PubMed Identifier
28455343
Citation
Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, Drazner MH, Filippatos GS, Fonarow GC, Givertz MM, Hollenberg SM, Lindenfeld J, Masoudi FA, McBride PE, Peterson PN, Stevenson LW, Westlake C. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017 Aug 8;136(6):e137-e161. doi: 10.1161/CIR.0000000000000509. Epub 2017 Apr 28. No abstract available.
Results Reference
background
PubMed Identifier
28369313
Citation
Corrigendum to: 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2018 Apr 1;39(13):1109. doi: 10.1093/eurheartj/ehx039. No abstract available.
Results Reference
background
PubMed Identifier
31017637
Citation
Greenberg B, Neaton JD, Anker SD, Byra WM, Cleland JGF, Deng H, Fu M, La Police DA, Lam CSP, Mehra MR, Nessel CC, Spiro TE, van Veldhuisen DJ, Vanden Boom CM, Zannad F. Association of Rivaroxaban With Thromboembolic Events in Patients With Heart Failure, Coronary Disease, and Sinus Rhythm: A Post Hoc Analysis of the COMMANDER HF Trial. JAMA Cardiol. 2019 Jun 1;4(6):515-523. doi: 10.1001/jamacardio.2019.1049.
Results Reference
background
PubMed Identifier
30146935
Citation
Zannad F, Anker SD, Byra WM, Cleland JGF, Fu M, Gheorghiade M, Lam CSP, Mehra MR, Neaton JD, Nessel CC, Spiro TE, van Veldhuisen DJ, Greenberg B; COMMANDER HF Investigators. Rivaroxaban in Patients with Heart Failure, Sinus Rhythm, and Coronary Disease. N Engl J Med. 2018 Oct 4;379(14):1332-1342. doi: 10.1056/NEJMoa1808848. Epub 2018 Aug 27.
Results Reference
background
PubMed Identifier
21830957
Citation
Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sep 8;365(10):883-91. doi: 10.1056/NEJMoa1009638. Epub 2011 Aug 10.
Results Reference
background
PubMed Identifier
27938741
Citation
Noseworthy PA, Yao X, Abraham NS, Sangaralingham LR, McBane RD, Shah ND. Direct Comparison of Dabigatran, Rivaroxaban, and Apixaban for Effectiveness and Safety in Nonvalvular Atrial Fibrillation. Chest. 2016 Dec;150(6):1302-1312. doi: 10.1016/j.chest.2016.07.013. Epub 2016 Sep 28.
Results Reference
background
PubMed Identifier
26318604
Citation
Melgaard L, Gorst-Rasmussen A, Lane DA, Rasmussen LH, Larsen TB, Lip GY. Assessment of the CHA2DS2-VASc Score in Predicting Ischemic Stroke, Thromboembolism, and Death in Patients With Heart Failure With and Without Atrial Fibrillation. JAMA. 2015 Sep 8;314(10):1030-8. doi: 10.1001/jama.2015.10725.
Results Reference
background
PubMed Identifier
31461239
Citation
Mehra MR, Vaduganathan M, Fu M, Ferreira JP, Anker SD, Cleland JGF, Lam CSP, van Veldhuisen DJ, Byra WM, Spiro TE, Deng H, Zannad F, Greenberg B. A comprehensive analysis of the effects of rivaroxaban on stroke or transient ischaemic attack in patients with heart failure, coronary artery disease, and sinus rhythm: the COMMANDER HF trial. Eur Heart J. 2019 Nov 21;40(44):3593-3602. doi: 10.1093/eurheartj/ehz427.
Results Reference
background
PubMed Identifier
22773537
Citation
Lip GY, Rasmussen LH, Skjoth F, Overvad K, Larsen TB. Stroke and mortality in patients with incident heart failure: the Diet, Cancer and Health (DCH) cohort study. BMJ Open. 2012 Jul 7;2(4):e000975. doi: 10.1136/bmjopen-2012-000975. Print 2012.
Results Reference
background
PubMed Identifier
21061046
Citation
Alberts VP, Bos MJ, Koudstaal P, Hofman A, Witteman JC, Stricker B, Breteler M. Heart failure and the risk of stroke: the Rotterdam Study. Eur J Epidemiol. 2010 Nov;25(11):807-12. doi: 10.1007/s10654-010-9520-y.
Results Reference
background
PubMed Identifier
16824838
Citation
Witt BJ, Brown RD Jr, Jacobsen SJ, Weston SA, Ballman KV, Meverden RA, Roger VL. Ischemic stroke after heart failure: a community-based study. Am Heart J. 2006 Jul;152(1):102-9. doi: 10.1016/j.ahj.2005.10.018.
Results Reference
background
PubMed Identifier
24165909
Citation
Hassell ME, Nijveldt R, Roos YB, Majoie CB, Hamon M, Piek JJ, Delewi R. Silent cerebral infarcts associated with cardiac disease and procedures. Nat Rev Cardiol. 2013 Dec;10(12):696-706. doi: 10.1038/nrcardio.2013.162. Epub 2013 Oct 29.
Results Reference
background
PubMed Identifier
21870978
Citation
Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92. doi: 10.1056/NEJMoa1107039. Epub 2011 Aug 27.
Results Reference
background
PubMed Identifier
31816553
Citation
Jansson M, Sjalander S, Sjogren V, Renlund H, Norrving B, Sjalander A. Direct comparisons of effectiveness and safety of treatment with Apixaban, Dabigatran and Rivaroxaban in atrial fibrillation. Thromb Res. 2020 Jan;185:135-141. doi: 10.1016/j.thromres.2019.11.010. Epub 2019 Nov 13.
Results Reference
background
PubMed Identifier
31044227
Citation
Kim BJ, Kwon SU, Park JM, Hwang YH, Heo SH, Rha JH, Lee J, Park MS, Kim JT, Song HJ, Park JH, Yu S, Lee SJ, Park TH, Cha JK, Kwon HM, Kim EG, Lee SH, Lee JS, Lee J, Kang DW. Blood Pressure Variability Is Associated With White Matter Lesion Growth in Intracranial Atherosclerosis. Am J Hypertens. 2019 Aug 14;32(9):918-924. doi: 10.1093/ajh/hpz068.
Results Reference
background

Learn more about this trial

Effects of APIXaban on BRAIN Protection in Patients With Sinus Rhythm and Heart Failure: APIXBRAIN-HF Trial

We'll reach out to this number within 24 hrs