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Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation (ARTESiA)

This study is currently recruiting participants.
Verified May 2017 by Jeff Healey, Population Health Research Institute
Sponsor:
ClinicalTrials.gov Identifier:
NCT01938248
First Posted: September 10, 2013
Last Update Posted: May 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Bristol-Myers Squibb
Pfizer
Medtronic
Canadian Institutes of Health Research (CIHR)
Hamilton Health Sciences Research Institute
Hamilton Health Sciences Foundation
Information provided by (Responsible Party):
Jeff Healey, Population Health Research Institute
  Purpose
This study aims to determine if treatment with apixaban, compared with aspirin, will reduce the risk of ischemic stroke and systemic embolism in patients with device-detected sub-clinical atrial fibrillation and additional risk factors for stroke.

Condition Intervention Phase
Atrial Fibrillation Stroke Drug: Apixaban Drug: aspirin Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation

Resource links provided by NLM:


Further study details as provided by Jeff Healey, Population Health Research Institute:

Primary Outcome Measures:
  • Composite of ischemic stroke and systemic embolism [ Time Frame: event driven, duration of follow-up - mean follow-up time anticipated: 3 years ]

    Definition of stroke:

    1. Rapid onset* of a focal/global neurological deficit
    2. Duration of a focal/global neurological deficit ≥ 24 hours OR the neurological deficit results in death OR the neurological deficit is supported by clear evidence of cerebral infarction on diffusion-weighted MRI imaging.
    3. No other readily identifiable non-stroke cause for the clinical presentation
    4. Confirmation of the diagnosis by specialist evaluation or brain imaging procedure

    Definition of Systemic Embolism:

    Clinical signs and symptoms consistent with embolic arterial occlusion plus at least one of the following objective findings of arterial embolism:

    • Surgical report indicating evidence of arterial embolism
    • Pathological specimens related to embolism removal
    • Imaging evidence consistent with arterial embolism
    • Autopsy reports

  • Major Bleed [ Time Frame: duration of follow-up ]

    The main safety outcome will be the occurrence of clinically overt major bleeding as defined by the ISTH criteria:

    1. Fatal bleeding, and/or
    2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or
    3. Bleeding causing a fall in hemoglobin level of 2 g/dL or more, or leading to transfusion of two or more units of whole blood or red cells.


Secondary Outcome Measures:
  • Ischemic Stroke [ Time Frame: Duration of Follow-up ]
  • Myocardial Infarction [ Time Frame: Duration of follow-up ]

    MI definition:

    1. Typical rise and gradual fall (troponin) or more rapid rise and fall (CKMB) of biochemical markers of myocardial necrosis with at least one of: a) ischemic symptoms; b) development of pathological Q-waves on the ECG; c) ECG changes indicative of ischemia; d) Coronary artery intervention

      OR

    2. Pathological findings of an acute myocardial infarction

  • Cardiovascular Death [ Time Frame: Duration of follow-up ]
  • All-cause Death [ Time Frame: Duration of follow-up ]
  • Composite of stroke, MI, SE and death [ Time Frame: Duration of follow-up ]
    Composite of stroke, myocardial infarction, systemic embolism and all-cause death

  • Composite of stroke, MI, SE, death and major bleeding [ Time Frame: Duration of follow-up ]
    Composite of stroke, myocardial infarction, systemic embolism, all-cause death and major bleeding


Estimated Enrollment: 4000
Actual Study Start Date: May 2015
Estimated Study Completion Date: April 2021
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Control
Aspirin 81 mg once daily
Drug: aspirin
aspirin 81 mg once daily
Other Names:
  • ASA
  • acetylsalicylic acid
Experimental: Intervention
Apixaban, 5 mg twice daily (or 2.5 mg twice daily if 2 or more of: age > 80, weight ≤ 60 kg or serum creatinine ≥ 133 mmol/L)
Drug: Apixaban
apixaban at a dose of 5 mg twice daily (2.5 mg twice daily if 2 or more of: age > 80, weight ≤ 60 kg or serum creatinine ≥ 133 mmol/L)
Other Name: Eliquis

Detailed Description:

Device-detected sub-clinical atrial fibrillation (SCAF) is a new disorder that has been recognized since the availability of implantable devices capable of long term continuous heart rhythm monitoring. It is characterized by one or more runs of rapid atrial arrhythmia detected by the device without symptoms and without any clinical atrial fibrillation (AF) detected by the usual methods, (i.e. electrocardiogram, Holter monitor, etc.). In the ASSERT trial, SCAF was detected by a pacemaker or implantable cardioverter defibrillator (ICD) in nearly 40% of patients during 2 and a half years of follow up. The presence of SCAF increased stroke risk by 2.5-fold (1). The risk of stroke or systemic embolism among patients with SCAF and a CHADS2 score ≥ 4 was 2.75% per year. Oral anticoagulation is effective and safe for stroke prevention in patients with clinical atrial fibrillation, but it is unknown if the same risk benefit ratio exists for anticoagulation therapy in patients with SCAF (2;3). SCAF differs from clinical AF in being of shorter duration, being asymptomatic, and often have a more regular rhythm in the right atrium where it is typically detected. Data ASSERT suggest that the increase in stroke risk with SCAF may be less than the increase with clinical AF. Therefore opinion leaders have written that the role of oral anticoagulation for the treatment of SCAF is uncertain and that randomized trials of anticoagulation are needed (4;5). Recent surveys of pacemaker clinic practice indicate that only 25% of patients with SCAF are treated with oral anticoagulation (6;7). Thus there is clinical equipoise for a trial of oral anticoagulation compared to aspirin in higher risk patients with SCAF.

Apixaban is a Factor Xa inhibitor that is an effective and safe anticoagulant. It has been shown to have an excellent risk benefit profile for stroke prevention in clinical AF (14, 15). It is highly suitable to test if oral anticoagulation therapy will reduce the risk of stroke or systemic embolism in SCAF.

Patients will be randomized double-blind to receive apixaban or aspirin. Apixaban dose will be 5 mg twice daily (2.5 mg twice daily if 2 or more of: age > 80, weight ≤ 60 kg or serum creatinine ≥ 133 mmol/L). Those assigned to aspirin will receive a dose of 81 mg daily. The study will be event driven and will continue until 248 patients have experienced a primary outcome event.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   55 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Permanent pacemaker or defibrillator (with or without resynchronization) or insertable cardiac monitor capable of detecting SCAF
  2. At least one episode of SCAF ≥ 6 minutes in duration but no single episode > 24 hours in duration at any time prior to enrollment. Any atrial high rate episode with average > 175 beats/min will be considered as SCAF. No distinction will be made between atrial fibrillation and atrial flutter. SCAF requires electrogram confirmation (at least one episode) unless ≥ 6 hours in duration.
  3. Age ≥ 55 years
  4. Risk Factor(s) for Stroke:

Previous stroke, TIA or systemic arterial embolism OR Age at least 75 OR Age 65-74 with at least 2 other risk factors OR Age 55-64 with at least 3 other risk factors

Other risk factors are:

  • hypertension
  • CHF
  • diabetes
  • vascular disease (i.e. CAD, PAD or Aortic Plaque)
  • female

Exclusion Criteria:

  1. Clinical atrial fibrillation documented by surface ECG (12 lead ECG, Telemetry, Holter) lasting ≥ 6 minutes, with or without clinical symptoms
  2. Mechanical valve prosthesis, deep vein thrombosis, recent pulmonary embolism or other condition requiring treatment with an anticoagulant
  3. Contra-indication to apixaban or aspirin:

    1. Allergy to aspirin or apixaban
    2. Severe renal insufficiency (creatinine clearance must be calculated in all patients; any patient with either a serum creatinine > 2.5 mg/dL [221 µmol/L] or a calculated creatinine clearance < 25 ml/min is excluded)
    3. Serious bleeding in the last 6 months or at high risk of bleeding (this includes, but is not limited to: prior intracranial hemorrhage, active peptic ulcer disease, platelet count < 50,000/mm3 or hemoglobin < 10 g/dL, recent stroke within past 10 days, documented hemorrhagic tendencies or blood dyscrasias)
    4. Moderate to severe hepatic impairment
    5. Ongoing need for combination therapy with aspirin and clopidogrel (or other combination of two platelet inhibitors)
    6. Meets criteria for requiring lower dose of apixaban AND also has ongoing need for strong inhibitors of CYP 3A4 or P-glycoprotein (e.g., ketoconazole, itraconazole, ritonavir or clarithromycin)
    7. Ongoing need for strong dual inducers of CYP 3A4 or P-glycoprotein (e.g., rifampin, carbamazepine, phenytoin, St. John's wort)
  4. Received an investigational drug in the past 30 days
  5. Participants considered by the investigator to be unsuitable for the study for any of the following reasons:

    1. Not agreeable for treatment with either aspirin or apixaban or anticipated to have poor compliance on study drug treatment
    2. Unwilling to attend study follow-up visits
    3. Life expectancy less than the expected duration of the trial2 years due to concomitant disease
  6. Women who are pregnant, breast-feeding or of child-bearing potential without an acceptable form of contraception in place (sterilization, hormonal contraceptives, intrauterine device, barrier methods or abstinence)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01938248


Contacts
Contact: Kim Simek 905-527-4322 ext 40524 kim.simek@phri.ca
Contact: Toni Newman 905-527-4322 ext 40633 toni.newman@phri.ca

  Hide Study Locations
Locations
United States, Arizona
Cardiovascular Associates of Mesa, PC Recruiting
Mesa, Arizona, United States, 85206
United States, Arkansas
St. Vincent Heart Clinic Recruiting
Little Rock, Arkansas, United States, 72205
United States, California
Cardiovascular Associates of Marin and San Francisco Medical Terminated
Larkspur, California, United States, 94939
United States, Colorado
Aurora Denver Cardiology Associates Recruiting
Aurora, Colorado, United States, 80012
United States, Florida
Naples Interventional Cardiac Electrophysiology Recruiting
Naples, Florida, United States, 34102
Langhorne Cardiology Consultants, Inc. Recruiting
Pensacola, Florida, United States, 32501
United States, Kentucky
One Health Cardiology, Owensboro Health, Inc. Recruiting
Owensboro, Kentucky, United States, 42304
United States, Massachusetts
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
United States, Michigan
Sparrow Clinical Research Institute Recruiting
Lansing, Michigan, United States, 48912
Michigan Heart Recruiting
Ypsilanti, Michigan, United States, 48197
United States, Missouri
University of Missouri Health System Recruiting
Columbia, Missouri, United States, 65212
St. Louis Heart and Vascular Recruiting
Saint Louis, Missouri, United States, 63136
United States, Montana
Glacier View Cardiology Recruiting
Kalispell, Montana, United States, 59901
United States, New Jersey
The Cooper Health System Recruiting
Camden, New Jersey, United States, 08103
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
The Valley Hospital Recruiting
Ridgewood, New Jersey, United States, 07450
United States, New York
St. Peter's Health Partners Medical Association, PC Recruiting
Albany, New York, United States, 12205
United States, North Carolina
Carolinas Healthcare System Recruiting
Charlotte, North Carolina, United States, 28203
WakeMed Recruiting
Raleigh, North Carolina, United States, 27610
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Pennsylvania State University Recruiting
Hershey, Pennsylvania, United States, 17033
Research Institute of LG Health / Penn Medicine Recruiting
Lancaster, Pennsylvania, United States, 17602
United States, Virginia
Virginia Heart Recruiting
Falls Church, Virginia, United States, 22042
Belgium
Onze Lieve Vrouw Ziekenhuis Recruiting
Aalst, Belgium, 9300
Vivalia CSL St. Joseph Recruiting
Arlon, Belgium, 6700
Clinique Saint Jean-Brussels Recruiting
Brussels, Belgium, 1000
Grand Hopital de Charleroi Recruiting
Gilly, Belgium, 6060
AZ Groeninge Recruiting
Kortrijk, Belgium, 8500
University Hospitals Leuven Recruiting
Leuven, Belgium, 3000
CHC Saint Joseph Recruiting
Liege, Belgium, 4000
CHR de la Citadelle Recruiting
Liège, Belgium, 4000
AZ Delta Recruiting
Roeselare, Belgium, 8800
CHU Dinant-Godinne Recruiting
Yvoir, Belgium, 5530
Canada, Alberta
University of Calgary Foothills Hospital Recruiting
Calgary, Alberta, Canada, T2N 2T9
Royal Alexandra Hospital Recruiting
Edmonton, Alberta, Canada, T5H 3V9
University of Alberta Hospital Recruiting
Edmonton, Alberta, Canada, T6G 2B7
Grey Nuns Hospital Recruiting
Edmonton, Alberta, Canada, T6L 5X8
Canada, British Columbia
Heart Rhythm Research Office - St. Paul's Hospital Recruiting
Vancouver, British Columbia, Canada, V6E 1M7
Victoria Cardiac Arrhythmia Trials, Inc. Recruiting
Victoria, British Columbia, Canada, V8T 1Z4
Canada, Manitoba
St. Boniface Hospital Recruiting
Winnepeg, Manitoba, Canada, R2H 2A6
Canada, Nova Scotia
Capital District Health Authority Recruiting
Halifax, Nova Scotia, Canada
Canada, Ontario
Hamilton General Hospital Recruiting
Hamilton, Ontario, Canada, L8L 2X2
St. Mary's General Hospital Recruiting
Kitchener, Ontario, Canada, N2M 1B2
London Health Sciences Centre Recruiting
London, Ontario, Canada
Southlake Regional Health Centre Recruiting
Newmarket, Ontario, Canada
Oakville Cardiologists Recruiting
Oakville, Ontario, Canada
University of Ottawa Heart Institute Recruiting
Ottawa, Ontario, Canada
Health Sciences North Terminated
Sudbury, Ontario, Canada, P3E 5J1
St. Michael's Hospital Recruiting
Toronto, Ontario, Canada
Sunnybrook Hospital Recruiting
Toronto, Ontario, Canada
Canada, Quebec
Institute Universitaire de Cardiologie and de Pneumonologie Recruiting
Laval, Quebec, Canada
McGill University Health Centre Recruiting
Montreal, Quebec, Canada, H3G 1A4
CHUM - Hotel Dieu Recruiting
Montreal, Quebec, Canada
Hopital Sacre-Coeur de Montreal Recruiting
Montreal, Quebec, Canada
Montreal Heart Institute Recruiting
Montreal, Quebec, Canada
CHUS - Sherbrooke Recruiting
Sherbrooke, Quebec, Canada
Ciusss McQ Recruiting
Trois-Rivières, Quebec, Canada, G8Z 3R9
Czechia
IKEM Institute for Clinical and Experimental Medicine Recruiting
Prague, Czechia, 14021
Denmark
Hilleroed Hospital Recruiting
Hilleroed, North Zealand, Denmark, 3400
Sygehus Sonderjylland Recruiting
Aabenraa, Denmark, 6200
Aalborg University Hospital, Dept of Cardiology Recruiting
Aalborg, Denmark, 9000
Aarhus Unniversity Hospital, Skejby Recruiting
Aarhus, Denmark, DK-8200
Gentofte Hospital Recruiting
Hellerup, Denmark, 2900
Odense University Hospital Recruiting
Odense, Denmark, 5000
Hjertemedicinsk Forskning, RH Viborg, HEM Recruiting
Viborg, Denmark, 8800
Germany
Johann Wolfgang Goethe University Hospital Frankfurt Recruiting
Frankfurt, Hesse, Germany, 60590
Katholisches Klinikum Mainz Recruiting
Mainz, Rheinland-Pfalz, Germany, 55131
Universitatsklinikum des Saarlandes Recruiting
Homburg/Saar, Saarland, Germany, 66421
MVZ am Kuchwald GmbH Recruiting
Chemnitz, Saxony, Germany, 09113
Zentrum fur klinische Prufungen in der Facharztzentrum Dresd Recruiting
Dresden, Saxony, Germany, 01099
University Medicine Gottingen Recruiting
Gottingen, Germany, 37075
Asklepios Klinik Barmbek Recruiting
Hamburg, Germany, 22291
Universitaetsklinikum Tuebingen, Kardiologie Recruiting
Tuebingen, Germany, 72076
Hungary
Allami Szivkorhaz Balatonfured Recruiting
Balatonfured, Veszprem, Hungary, 8230
Magyar Honvedseg Egeszsegugyi Kozpont Recruiting
Budapest, Hungary, 1134
Semmelweis University Recruiting
Budapest, Hungary, H-1122
Italy
Ospedale Sant'Anna Recruiting
San fermo della Batt, Como, Italy, 22020
Cardiologia-A.O. Desio e Vimercate - Presisio di Vimercat Recruiting
Vimercate, Monza Brianza MB, Italy, 20871
Hospital Santa Maria Della Pieta Recruiting
Nola, Napoli, Italy, 80035
AOU Ospedali Riuniti Recruiting
Ancona, Italy, 60126
Ospedale Maggiore, Cardiologia Dept. Recruiting
Bologna, Italy, 40133
S.Orsola-Malpighi Recruiting
Bologna, Italy, 40138
Bolzano Regional Hospital, Dept of Cardiology Recruiting
Bolzano, Italy, 39100
Azienda Ospedaliero-Univeritaria Di Modena-Policlinico Recruiting
Modena, Italy, 41124
Ospedale G.B. Grassi Recruiting
Rome, Italy, 00122
University and Hospital of Trieste Recruiting
Trieste, Italy, 34129
Netherlands
Ziekenhuis Tjongerschans Recruiting
Heerenveen, Friesland, Netherlands, 8441 PW
Gelre Ziekenhuis Recruiting
Zutphen, Gelderland, Netherlands, 7207 AE
Atrium Orbis Heerlen Recruiting
Heerlen, Limburg, Netherlands, 6419 PC
Amphia Hospital Breda Recruiting
Breda, Noord-Brabant, Netherlands, 4818 CK
Ikazia Ziekenhuis Recruiting
Rotterdam, Zuid-Holland, Netherlands, 3083 AN
BovenIJ Ziekenhuis Recruiting
Amsterdam, Netherlands, 1034 CS
Hospital Rijnstate Recruiting
Arnhem, Netherlands, 6815 AD
Deventer Hospital, Cardiology Research Recruiting
Deventer, Netherlands, 7416 SE
Hospital Gelderse Vallei Recruiting
Ede, Netherlands, 6721 JT
Treant Hospital Department Cardiology Recruiting
Emmen, Netherlands, 7824 AA
Admiraal de Ruyter Ziekenhuis Recruiting
Goes, Netherlands, 4462 RA
Treant Hospital - Bethseda, Hoogeveen Recruiting
Hoogeveen, Netherlands, 7909 AA
Bravis Ziekenhuis, locatie Roosendaal Recruiting
Roosendaal, Netherlands, 4708 AE
(ETZ) Elisabeth Tweesteden Hospital Recruiting
Tilburg, Netherlands, 5022 GC
Máxima Medisch Centrum Recruiting
Veldhoven, Netherlands, 5504 DB
Norway
Barum Hospital, Vestre Viken Recruiting
Drammen, Buskerud, Norway, 3004
Oslo University Hospital - Ulleval Recruiting
Oslo, Norway, 0450
Spain
Hospital Clinico Santiago de Compostela Recruiting
Santiago de Composte, A Coruna, Spain, 15706
Rafael Mendez Universitary Hospital Recruiting
Lorca, Murcia, Spain, 30800
Complexo Hospitalario Universitario A Coruna Recruiting
A Coruna, Spain, 15006
Hospital General Universitario de Alicante Recruiting
Alicante, Spain, 03010
Hospital Del Mar Recruiting
Barcelona, Spain, 8003
Hospital Juan Ramon Jimenez Recruiting
Huelva, Spain, 21005
Hospital Clinico San Carlos, Unidad De Arritmias Recruiting
Madrid, Spain, 28040
Hospital Universitario Fundacion Jimenez Diaz Recruiting
Madrid, Spain, 28040
Hospital Puerta de Hierro Majadahonda Recruiting
Majadahonda, Spain, 28222
Agencia Sanitaria Costa del Sol- Hospital Costa del Sol Recruiting
Marbella, Spain, 29603
Clinica Universidad de Navarra Recruiting
Pamplona, Spain, 31008
Hospital Clinico Universitario de Valencia Recruiting
Valencia, Spain, 46010
Hospital Clínico Universitario de Valladolid Recruiting
Valladolid, Spain, 47003
Switzerland
University Hospital Basel Recruiting
Basel, Basel-Stadt, Switzerland, 4031
CHUV Recruiting
Lausanne, Vaud, Switzerland, 1011
Hopital Fribourgeois, site de Fribourg Recruiting
Fribourg, Switzerland, 1708
University Hospital of Geneva Recruiting
Geneva, Switzerland, 1211
Kantonsspital St Gallen Recruiting
St. Gallen, Switzerland, 9007
United Kingdom
Dorset County Hospital NHS Foundation Trust Recruiting
Dorchester, Dorset, United Kingdom, DT12JY
Hampshire Hospitals (NHS Foundation Trust) Recruiting
Basingstoke, Hampshire, United Kingdom, RG24 9NA
Portsmouth Hospitals NHS Trust Recruiting
Portsmouth, Hampshire, United Kingdom, PO6 3LY
Royal Alexandra Hospital Recruiting
Paisley, Renfrewshire, United Kingdom, PA29PN
Shrewsbury & Telford Hospital NHS Recruiting
Shropshire, West Midlands, United Kingdom, TF1 6TF
Blackpool Teaching Hospitals NHS Foundation Trust Recruiting
Blackpool, United Kingdom, FY3 8NR
Queen Elizabeth University Hospital Recruiting
Glasgow, United Kingdom, G51 4TF
Liverpool Heart and Chest Hospital Recruiting
Liverpool, United Kingdom, L14 3PE
Freeman Hospital Recruiting
Newcastle-upon-Tyne, United Kingdom, NE7 7DN
Sponsors and Collaborators
Population Health Research Institute
Bristol-Myers Squibb
Pfizer
Medtronic
Canadian Institutes of Health Research (CIHR)
Hamilton Health Sciences Research Institute
Hamilton Health Sciences Foundation
Investigators
Principal Investigator: Jeff Healey, M.D. Population Health Research Institute
Study Chair: Stuart Connolly, M.D. Population Health Research Institute
Principal Investigator: Marco Alings, M.D. Working Group Cardiovascular Research Netherlands
Principal Investigator: Renato Lopes, M.D. Duke Clinical Research Institute
  More Information

Responsible Party: Jeff Healey, Principal Investigator, Population Health Research Institute
ClinicalTrials.gov Identifier: NCT01938248     History of Changes
Other Study ID Numbers: ARTESiA
2014-001397-33 ( EudraCT Number )
First Submitted: September 4, 2013
First Posted: September 10, 2013
Last Update Posted: May 30, 2017
Last Verified: May 2017

Keywords provided by Jeff Healey, Population Health Research Institute:
Pacemaker, Artificial
Defibrillators, Implantable
Atrial Fibrillation
Stroke Risk

Additional relevant MeSH terms:
Atrial Fibrillation
Embolism
Thromboembolism
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Aspirin
Apixaban
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors