Supplementary Appendix

Supplement to: Healey JS, Lopes RD, Granger CB, et al. Apixaban for stroke prevention in subclinical atrial fibril-
lation. N Engl J Med. DOI: 10.1056/NEJMoa2310234

This appendix has been provided by the authors to give readers additional information about the work.
ARTESIA: Supplemental Appendix

1. Committee membership and List of ARTESIA Investigators

2. CONSORT Diagram
3. Supplemental Table S1: On the representativeness of study participants
4. Supplemental Table S2. Efficacy Outcome WITHOUT censoring for SCAF > 24 hours or clinical AF
5. Summary of Severe Adverse Events
 Committee membership and List of ARTESIA Investigators

Steering Committee

Jeff S. Healey, Renato D. Lopes, Chris B. Granger, Marco A. Alings, Lena Rivard, William F.
McInytre, Dan Atar, David H. Birnie, Giuseppe Boriani, John Camm, David Conen, Julia W. Erath,
Michael R. Gold, Stefan Hohnloser, John Ip, Josef Kautzner, Valentina Kutyifa, Cecilia Linde,
Philippe Mabo, Georges Mairesse, Juan Benezet Mazuecos, Jens Cosedis Nielsen, Francois
Philippon, Marco Proietti, Christian Sticherling, Jorge Wong, David J. Wright, Randy Zarraga,
Shelagh Coutts, Lizhen Xu, Kim Simek, Sandra Nevills, and Stuart J. Connolly.

Data Safety Monitoring Committee

John Cairns (Chair), Michael D. Hill, Harry R Büller, Oscar Benavente, Andrew Epstein.

Adjudication Committee

Shelagh B. Coutts (Chair), Thalia S. Field, David J. Gladstone, Ashkan Shoamanesh, Mukul Sharma,
Deborah Siegel, David Conen, William F. McIntyre

Total Enrolment by Country

Austria 44, Belgium 193, Canada 1002, Czech Republic 49, Denmark 218, France 70, Germany
116, Hungary 134, Italy 273, the Netherlands 280, Norway 32, Spain 431, Sweden 45,
Switzerland 77, UK 125, USA 923.

ARTESIA Investigators

Country Institution Name Name One Name Two

AT Ordensklinikum Linz GmbH Elisabethinen Dr. Michael Derndorfer Barbara Bichler

AT Medical University of Vienna Dr. Alexander Niessner Patrick Sulzgruber

AT Landesklinikum Wiener Neustadt Dr. Franz Roithinger Lukas Fiedler
BE Cliniques du Sud Luxembourg, Vivalia – Arlon Prof. Georges H. Mairess Annick Bartholome

BE CHU Dinant-Godinne Prof. Dominique Blommaert Elisabeth Ballant

BE CHC MontLégia, Liège Dr. Philippe Evrard Mrs. Ludivine Collard

BE AZ Groeninge Dr. Tim Boussy Mrs. Sarah Naessens

BE Onze Lieve Vrouw Ziekenhuis Dr. Tom De Potter Hedwig Batjoens

BE Clinique Saint Jean Dr. Philippe Purnode Ms. Severine Tahon

BE AZ Delta Dr. Wim Anne Ms. Anne Dewispelaere

BE Grand Hopital de Charleroi-St Joseph Dr. Jean Leroy Mrs. Amandine Jourdan

BE CHR de la Citadelle Dr. Etienne Hoffer Ms. Mireille Massoz

BE University Hospitals Leuven Dr. Thomas Vanassche Kristine Vanheule

BE ISPPC-CHU Charleroi-HCMC Dr. Ivan Blankoff Asuncion Conde Y Bolado

BE AZ Klina, Brasschaat Dr. Frank Cools Dr. Dieter De Cleen

BE Algemeen Stedelijk Ziekenhuis Dr. Philippe Vanduynhoven Lies DeHauwere

BE Az Sint Blasius Hospital, Dendermonde Dr. Tom Sarens Fritz Loth

CA Hamilton Health Sciences-HGH Dr. Guy Amit Andrea Afinec

CA St. Michael's Hospital Dr. Paul Angaran Marta Gadacz

CA University of Ottawa Heart Institute Dr. Calum Redpath Nancy Page

University Health Network,
CA Dr. Andrew C.T. Ha
Toronto General Hospital
CA Sunnybrook Health Sciences Centre Dr. Eugene Crystal Fahema Ahmadzai

CA QEII Health Sciences Center, Halifax Dr. Ratika Parkash Katie Kawulka
CA Southlake Regional Health Centre Dr. Bernice Tsang Lynn Nyman

CA McGill University Health Centre Dr. Vidal Essebag Dr Martin L. Bernier

CA CHUM_Recherche cardiologie Dr. Benoit Coutu Isabelle Denis
CA IUCPQ Dr. Jean-Francois Sarrazin Dr. Christian Steinberg

CA CHUS - Hopital Fleurimont Sherbrooke Dr. Felix Ayala-Paredes Caroline A. Lamoureux

CA St. Boniface Hospital Dr. Clarence Khoo Mrs. Maria Higgins

CA Montreal Heart Institute Dr. Lena Rivard Karine Martin

CA Hôpital du Sacré-Coeur de Montréal Dr. Teresa Kus Ann Langlois
Alberta Health Services and
CA Dr. L. Brent Mitchell Sandra Rivest RN
University of Calgary
CA University of Alberta Hospital Dr. Roopinder K. Sandhu Dr. Kenneth Quadros
CA St. Mary's General Hospital Dr. Claus Rinne Ms. Irene Janzen

CA Royal Alexandra Dr. Evan Lockwood Rebecca Cairns

CA Grey Nuns Hospital Dr. Sajaad Gulamhusein Usha Chhetri

CA London Health Sciences Centre Dr. Peter Leong-Sit Samuel Triemstra

CA Oakville Cardiovascular Research LP Dr. Michael Heffernan Marie Birch

CA CIUSSS MCQ Dr. Miguel Barrero Martin Faucher

CA Victoria Cardiac Arrhythmia Trials, Inc. Dr. Laurence D. Sterns Jake Gray
CA St. Paul's Hospital Dr. Marc Deyell Elisa Ramser

CA Canada Heart Health Institute Research Inc. Dr. Bhavanesh Makanjee Dr. Derek Yung
CA Dr. Georges-L.-Dumont University Hospital Dr. Michel D'Astous Ms. Lola Ouellette-Bernier
CA Saint John Regional Hospital Dr. Satish Toal Satish Toal

CA Prairie Vascular Research Inc. Dr. Omar Sultan Brooke Bowles

CA Kingston General Hospital - CARU Dr. Adrian Baranchuk Elias Ordaz

CZ Military University Hospital Prague Dr. Patrik Jarkovsky Helena Jansova

CZ IKEM-Department of Cardiology Dr. Hanka Wunschova Anna Kuprova

CZ St. Ann Faculty Hospital, I. IKAK Dr. Miroslav Novak

Charles University in Prague and
CZ Dr. Petr Parizek Ms. Jana Cervena
University Hospital Hradec Kralove
CZ General University Hospital Dr. Sudheera Magage

DK Odense University Hospital Prof. Jens Brock Johansen Ida Rosenlund

DK Hilleroed Hospital Dr. Nis Ottesen Stride Ellen Mouritsen

DK Gentofte Hospital Dr. Jens Haarbo Ida-Maria Schiøtt-Hyldelund

DK Aalborg University Hospital Dr. Katja Fiedler Holm Anja Fladkjær Pedersen

DK Aarhus University Hospital Dr. Christoffer Tobias Witt Sonja Runge

DK Sygehus Sonderjylland Dr. Lene S. Christensen Rebekka Goos
DK Regional Hospital Viborg Dr. Andi Eie Albertsen Pia Saugmann

DK Hjerteforskningsklinikken Dr. Jerzy Malczynski Stine Sondergaard

FR Rouen University Hospital Prof. Frederic Anselme Audrey Delestre

FR CHU A. Michallon Prof. Pascale Defaye Sarah Limon

FR CH PAU Dr. Nicolas Delarche Aude Bernard

FR Nouvelles Cliniques Nantaises-NCN Dr. Daniel Gras Dr. Daniel Gras

FR Centre Cardiologique du Nord Dr. Olivier Piot Karima Moussouni

FR Clinique du Millenaire Dr. Maxime Pons Mrs. Amelie Lelievre

FR Hopital Henri Mondor Prof. Nicolas Lellouche Kamila Djouadi

FR Centre Hospitalier de Versailles Dr. Gianina Galuscan Jean-Baptiste Azowa

FR Centre Hospitalier Princesse Grace, Monaco Dr. Decebal Gabriel Latcu

FR Hopital Francois Mitterrand Prof. Yves Cottin Hamon Anais

FR Hopital Henri Duffaut Dr. Saida Cheggour Jose Sevilla

FR Saint Martin private hospital center Dr. Alain Lebon Dr. Sophie Gomes

DE Asklepios Klinik Barmbek Prof. Gerian Groenefeld Canan Kurnaz

DE Universitatsklinikum J-W Goethe Dr. Julia W. Erath Claudia Schwarzer

DE University Medicine Göttingen Prof. Rolf Wachter Mark Weber-Krüger
DE Evangelical Hospital Bielefeld Dr. Carsten W. Israel Andrea Lipinski

DE Marienhausklinikum Mainz Dr. Sabine Genth-Zotz Barbel Kaesberger

DE Zentrum fur klinische Prufungen dr. med. L. Karolyi Prof. S.G. Spitzer

DE Universitaetsklinikum Tuebingen Prof. Tobias Geisler Isabela Kast

DE MVZ am Kuchwald GmbH Dr. Wilfried Danschel Silke Geserick

DE University Hospital Ulm Dr. Carlo Bothner Sylvia Dippmann

DE Stadtisches Klinikum Dresden Prof. Sebastian Schellong Roswitha Frommhold

DE DRK Kliniken Berlin - Westend Prof. Sascha Rolf Melanie Beyer

DE Johannes Wesling Klinikum Minden Dr. Marcus Wiemer Alicia Hidalgo

DE Kerckhoff Klinik GmbH Prof. Christian Hamm Christine Scheld

HU Semmelweis University Prof. Bela Merkely Laura Dzsida

HU Allami Szivkorhaz Balatonfured Dr. Jozsef Falukozy Agnes Bathory
Central Hospital of Northern Pest - Military
HU Prof. Gabor Zoltan Duray Dr. Peter Bogyi
Hospital
HU University of Szeged Dr. Mate Vamos Marton Miklos
IT Federico II University Prof. Antonio Rapacciuolo Rosaria Chiappetti

IT Ospedale U. Parini Dr. Bruna Catuzzo Dr. Genny Jocolle

IT Sant Orsola-Malpighi-Bologna Dr. Igor Diemberger Ms. Jessica Frisoni

IT Bolzano Regional Hospital Dr. Massimiliano Manfrin Dr. Luca Donazzan

IT Ospedale G.B. Grassi Dr. Fabrizio Ammirati Dr. Nicola Danisi

IT University and Hospital of Trieste Dr. Massimo Zecchin

IT AOU Ospedali Riuniti Dr. Federico Guerra Dr. Alessandro Faggioni

IT Ospedale Maggiore Dr. Maurizio Landolina Dr. Enrico Chieffo

IT Ospedale di Camposampiero Dr. Roberto Verlato Sara De Bardi

IT Policlinico di Modena Dr. Jacopo F. Imberti Dr. Davide A. Mei

IT Ospedale Maggiore Dr. Francesco Pergolini Barbara Coutsoumbas

IT Ospedale S. Maria della Stella, Orvieto Dr. Andrea Mazza Lorena D'elia
ASST Grande Ospedale Metropolitano
IT Dr. Matteo Baroni Dr. Marco Carbonaro
Niguarda - Milan
IT Ospedale Mater Salutis Dr. Gabriele Zanotto Mr. Matteo Bozzolin
IT Sacro Cuore Hospital Dr. Giulio Molon Dr. Alessandro Costa

IT Fondazione IRCCS Policlinico S. Matteo Dr. Roberto Rordorf Andrea Camorani

NL Amphia Hospital, Breda Saskia Van Roij Ineke Lauwerijssen-de Regt
NL Maxima Medisch Centrum, Velhoven Dr. S.C.M. Eijsbouts M. Likkel

NL Hospital Gelderse Vallei Dr. Frank Den Hartog Desiree Van Wijk

NL Zuyderland M.C Dr. Bastiaan Kietselaer Pamela Kleikers

NL Reinier de Graaf Gasthuis Dr. Eelko Ronner Anita Wissenburg

NL Ziekenhuis Tjongerschans Dr. Remco Nijmeijer Reimke Binnema

NL Gelre Hospital Dr. Nadea Al-windy Lonneke Seffinga

NL Ikazia Ziekenhuis Dr. Stieneke Zoet-Nugteren Petra den Boer

NL St. Elizabeth Ziekenhuis Hospital Dr. Arjen C. B. Pronk Josephine de Loos

NL St Elizabeth TweeSteden Ziekenhuis Dr. Arjen C. B. Pronk Josephine de Loos

NL Treant Zorggroep - Scheper Dr. Tom D. J. Smilde Ms. Sanne van der Kooi

NL Admiraal de Ruyter Ziekenhuis Dr. Ismail Aksoy Brigitte Kool

NL Deventer Hospital, Deventer Dr. Ype S. Tuininga Dr. Erik Badings
NL Rijnstate Hospital Arnhem Dr. Martin Hemels
NL BovenIJ ziekenhuis Dr. Machiel van de Wetering Mrs. Marian Smit

NL Bravis Ziekenhuis Roosendaal Dr. Reinhart Dorman Bianca Tan-Urgert

NL Treant Hospital - Bethseda, Hoogeveen Dr. Tom D. J. Smilde Ms. Sanne van der Kooi

NL Diakonessenhuis Utrecht Dr. H.J. Houtgraaf Dr. C.E. van Ofwegen

NO Baerum Hospital Prof. Arnliot Tveit Mrs. Sofia Onarheim

NO Oslo University Hospital - Ulleval Prof. Torkel Steen Hilde Kristin Fosse
Dr. Jose Manuel Rubio
ES Hosp University Fundacion Jimenez Diaz Dr. Jose Iglesias Bravo
Campal
Hospital Universitario Puerta de Hierro
ES Dr. Jorge Toquero Dr. Eusebio Garcia-Izquierdo
Majadahonda, Madrid
ES Clinica Universidad De Navarra Dr. Pablo Ramos Ardanaz Dr. Ballesteros Derbenti

ES Hospital Clinico Universitario de Valenc Dr. Ricardo Ruiz Granell Laura De Las Heras

ES Complexo Hospitalario Universitario A Coruña Dr. Ignacio Mosquera Dr. Enrique Ricoy

ES UNIVERSITARIO DE ALICANTE Dr. Juan Gabriel Martinez Mrs. Raquel Ajo Ferrer
Dr. Juan Manuel Fernandez-
ES Hospital Juan Ramon Jimenez Dr. Rafael Barba Pichardo
Gome
Hospital Clínico San Carlos and Centro de
Investigación Biomédica en Red de
ES Dr. Nicasio Pérez-Castellano Dr. Julián Villacastín
Enfermedades Cardiovasculares (CIBERCV),
Madrid
ES Hospital Costa del Sol, Marbella (Malaga) Dr. Marta Pombo Almudena Valle
Cardiology Service, Hospital Clínico
ES Pablo E. Garcia-Granja Susana Bombin
Universitario de Valladolid, Valladolid
ES Hospital Clinico Santiago de Compostela Dr. Moises Rodriguez-Manero Ms. Ana Dominguez

ES Rafael Mendez University Hospital Dr. Silvestre Nicolas-Franco Dr. Julian Navarro

ES Hospital del Mar, Barcelona Dr. Ermengol Valles Carlos E. Gonzalez

ES Hospital 12 de Octubre Dr. Alvaro Marco del Castillo Pilar Gonzalez

ES Hospital Universitario Rey Juan Carlos Dr. Federico Gomez Pulido Dr. Elena Mejia Martinez

ES Hospital Manises Dr. Pau Alonso Paloma Oltra

ES Hospital Universitari Vall d'Hebron, Barcelona Dr. Jaume Francisco-Pascual Dra. Nuria Rivas-Gándara

ES Hospital Universitario La Luz, Madrid Dr. Juan Benezet-Mazuecos Dr. Jose Antonio Iglesias
Maria del Carmen de la
ES Hospital Universitario Son Espases, Palma Dr. Julián Palacios-Rubio
Bandera
SE Karolinska Hospital Dr. Fredrik Gadler Kerstin Hoglund

SE Sahlgrenska University Hospital Dr. Piotr Szamlewski Carola Gustafsson

SE Hjartmottagningen Hallands sjukhus Dr. Cecilia Rorsman Anette Andersson

CH Kantonsspital St Gallen Prof. Peter Ammann Susanne Vetsch

CH University Hospital of Geneva Dr. Haran Burri Nicolas Masson
CH Hopital Fribourgeois Dr. Denis Graf Ms. Helene Villeneuve

CH CHUV Dr. Etienne Pruvot Nathalie Lauriers

CH University Hospital Basel Dr. Pascal B. Meyre Dr. Elisa Hennings

CH University Hospital Zurich Dr. Alexander Breitenstein Ellen Saga

Freeman Hospital, Newcastle upon Tyne
UK Dr. Chris Plummer Ursula Harrison
Hospitals NHS Foundation Trust
UK Liverpool Heart and Chest Hospital Dr. DJ Wright Michail Sionas
UK Blackpool Victoria Hospital Dr. Christopher Cassidy Angelic Goode
UK Portsmouth Hospitals University NHS Trust Dr. Geraint Morton Mrs. Charlotte Turner

UK Hampshire Hospitals (NHS Trust) Dr. Jason Glover Angela Heath

UK George Eliot Hospital NHS Trust Dr. Asok Venkataraman Mrs. Judith Lake

UK St. Peter's Hospital (NHS Trust) Dr. Zhong Chen Ms. Elizabeth Cruddas

UK Salisbury NHS Foundation Trust Dr. Tim Wells Alpha Anthony

UK Cambridge University Hospitals (NHS FT) Dr. Peter Pugh Rebecca Thomas
Queen Elizabeth Queen Mother Hospital,
UK Dr. JA Rosengarten Dr. Eva Beranova
Margate
UK William Harvey Hospital, Ashford Dr. JA Rosengarten Mr. James Rand

US CardioVascular Associates of Mesa Dr. Andrew Kaplan Dr. Santosh Desai

US Cardiovascular Associates of Marin Dr. Margaret Baer

US Naples Int. Cardiac Electrophysiology Dr. Sinan Gursoy Ms. Sherie Kolakowski

US William Beaumont Hospital Dr. David Haines Jon Teefey

US WakeMed Dr. Marc Silver Ms. Rhonda Norton

US Hackensack University Medical Center Dr. Taya Glotzer Patricia Arakelian

US Cleveland Clinic Dr. Bruce Wilkoff Denielle Schaffer

US Penn State & Milton Hershey Med. Center Dr. Soraya Samii Katherine Loffredo

US University of Missouri Dr. Gregory Flaker Ms. Vickie Grieshaber

US St. Louis Heart and Vascular Dr. Rafiq Ramadan Marie Reno
Texas Cardiac Arrhythmia Research
US Dr. Patrick Hranitzky Deb Cardinal
Foundation
US Glacier View Research Institute Dr. Eve Gillespie Marci Fournier
US Aurora Denver Cardiology Associates Dr. Charles Fuenzalida Chris Dutka

US St. Vincent Heart Clinic Arkansas Dr. Thomas Wallace Gerry Carter
US St. Peter's Health Partners, PC Dr. Robert Phang Spencer Phelps
US CHS Sanger Heart & Vascular Institute Dr. Sherry Saxonhouse Yaritza De Los Santos

US Holy Cross Hospital Inc. Dr. Rishi Anand Christine Lepurage

US Cape Fear Heart Associates Dr. Meena Rao Janet Lockard

US Virginia Heart Dr. Anthony Chang Therese Del Castillo

US The Valley Hospital, Ridgewood, NJ Dr. Suneet Mittal Kimberly Michel

US Penn Medicine Lancaster General Health Dr. Sandeep Bansal Deborah Ramsey
US The Cooper Health System Dr. Andrea Russo Stephanie Vasey

US Tufts Medical Center Dr. Christopher Madias Laurie Butts

US Hospital of the University of Pennsylvania Dr. David S. Frankel Mary Gnap

US Langhorne Cardiology Consultants, Inc. Dr. Evan Giedrimas Tricia Parsons

US Baptist Health Lexington Dr. Gery Tomassoni Kristie Schneider

US Northside Hospital Dr. Robert Sheppard Michelle Nelson

US Redmond Regional Medical Center Dr. Robert Styperek Kathy Jones

US University of Rochester Medical Center Dr. David Huang Laura Wing

US Steward St. Elizabeth's Medical Center Dr. Michael Orlov Dr. John Wylie

US UMass Medical School Dr. Lawrence Rosenthal Alexander Schryver

US The Miriam Hospital Dr. Christopher Song Lori-Ann DeSimone
US Virginia Commonwealth University Dr. Kenneth Ellenbogen Esoterica Berry

US Maine Medical Center Dr. Andrew Corsello Joanne Burgess

US South Texas Cardiovascular Consultants Dr. Javier Roman-Gonzalez Stephanie Lambert

US University of Utah Dr. Benjamin Steinberg Jaymee Sanderson

US Bay Pines VAHCS, Bay Pines Country Dr. Afolabi Sangosanya Cortny Withee

US Sparrow Clinical Research Institute Dr. John Ip Jennifer Boak

US Michigan Heart Dr. Jihn Han Megan Thompson

US Ascension St. John Macomb Dr. Sohail Hassan Lauren Vitale

US Phoenix Heart PLLC Dr. Fred H. Cucher Jessica Frost
Medical University of South Carolina,
US Dr. Michael R Gold Deborah Everidge
Charleston
US EMMC Northeast Cardiology Associates Dr. Alan Wiseman Ms. Erin Seavey
US DBA Upstate Cardiology Dr. Gregory San Scott Boileau

US Gateway Cardiovascular Research, Inc. Dr. Liwa Younis Heidi O'Neal

US Radin Cardiovascular Medical Group Dr. Michael Radin Adriana Giron
US Brooke Army Medical Center Dr. Rosco Gore Genice Jacques

US University of Washington, Seattle Dr. Nazem Akoum Laura Curtin

US Prairie Education & Research Cooperative Dr. Bharath Rajagopalan Lauren Bainter

US Clinical Research UP Medical Office Building Dr. Mark Cowan Heather Shepard
US North Florida/South Georgia VA Dr. Mark Panna Ramil Goel

US The Heart Hospital Baylor Plano Dr. Hafiza Khan Penni Dolton
US Lindner Research Center-The Christ Hospital Dr. Edward Schloss Deborah Garza

US Ochsner Medical Center Dr. Freddy Abi-Samra Melanie Lunn

US Piedmont Heart Institute - Athens Dr. Kent Nilsson Heather Keperling

US The Cardiac & Vascular Institute (RF) Dr. Michael Jansen Ms. Abby Foster

US Minneapolis Heart Institute Foundation Dr. JoEllyn Moore Andrea Sarafolean

US Medstar Washington Hospital Center Dr. Zayd Eldadah Nebu Alexander

US Peak Clinical Trials Dr. Srivani Ambati

US William Beaumont Army Medical Center Dr. Courtney Usry

US Mount Sinai Hospital, New York Dr. William Whang Jeff Lam

US MidMichigan Medical Center - Midland Dr. Opesanmi Esan

US ProHealth Care, Inc. Dr. Jennifer D. Johnson Rita Shetty
US St. Vincent's Health System, Inc. Dr. Anthony Magnano Danielle Torres
University of California San Diego Health, La
US Dr. Jonathan C. Hsu Sandeep Toomu
Jolla
US MetroHealth Medical Center Dr. Elizabeth S. Kaufman Peter J. Leo, RN, BSc

US Medical City Dallas (Sarah Cannon) Dr. Jodie Hurwitz Mona Hedra

US Good Samaritan Hospital Dr. Marshall Winner Laurie Freel

US Cardiology Associates of Fairfield Dr. Edward Portnay Kiley Michaels
Rocky Mountain Regional VA Medical Center,
US Dr. Brack Hattler Jennifer Golden
Aurora, Colorado
North Memorial Health Heart & Vascular
US Dr. Ethan Fruechte Ann Antolick
Center
US Peace River Cardiovascular Center Dr. David Hotchkiss Amy King
US VA Portland Health Care System Dr. Ignatius Gerardo Zarraga Katie E. Lewis
US Veterans Research Foundation of Pittsburgh Dr. Alaa Shalaby Karen Gilbert
US Hunter Holmes McGuire VAMC Dr. Karoly Kaszala Kristina Baumgart

US Oregon Health and Science University Dr. Charles Henrikson Liz Cannard
US Atlanta VA Health Care System Dr. Heather Bloom Teclemichael Tewolde
US Va Loma Linda Healthcare System Dr. Ronald Lo Agnes Lee
US Charles George VA Medical Center Dr. Gregory Jones

US William S Middleton Veterans Hospital Dr. Matthew Kalscheur Lou Ellen Williams

US Tyler Cardiovascular Consultants, PA Dr. Raul Torres-Heisecke Elizabeth Seal

US John Cochran VA Dr. Molly Sachdev Gary Schofield

US George E Wahlen VA Hospital Dr. Scott Wall Kandi Velarde
US Ochsner Medical Center Baton Rouge Dr. Freddy Abi-Samra Johanna Veal

US University of Oklahoma Health Sciences Ctr. Dr. Stavros Stavrakis Michael Stout
 2. CONSORT Diagram
Randomized (ITT population, n=4012)
Randomized to Apixaban (n= 2015)
Did not receive study drug (n= 26)
Received allocated intervention
(TREATMENT RECEIVED, n= 1989)
Drug Discontinuations due to:
Clinical AF/SCAF>24hrs (n=490)
• AF on ECG (n=176)
• SCAF (n=314)
Other reasons:
Physician Decision (n=233)
Participant Decision (n= 283)
OAC for other (non-AF) indication: (n= 28)
Bleeding (n= 92)
Renal Function (n= 31)
Prohibited Concomitant Medication (n= 4)
Ineligible participant (n= 16)
Died (n= 457)
Lost to Follow up (n= 32)
Withdrawn Consent (n= 17)
Final Visit Completed (n= 1509)
Randomized to Aspirin (n= 1997)
Did not receive study drug (n=25)
Received allocated intervention
(TREATMENT RECEIVED, n= 1972)
Drug Discontinuations due to:
Clinical AF/SCAF>24hrs (n= 476)
• AF on ECG (n=177)
• SCAF (n=299)
Other reasons:
Physician Decision (n= 276)
Participant Decision (n= 292)
OAC for other (non-AF) indication: (n= 41)
Bleeding (n= 50)
Renal Function (n= 25)
Prohibited Concomitant Medication (n= 4)
Ineligible participant (n= 9)
Died (n= 438)
Lost to Follow up (n=33)
Withdrawn Consent (n=19)
Final Visit Completed (n=1507)
3. Supplemental Table S1: Of the representativeness of study participants

Disease under investigation Subclinical atrial fibrillation

Special considerations related to
Sex and gender Observational studies suggest that subclinical
atrial fibrillation similarly prevalent in females
and males.
Age The condition is more prevalent with advancing
age, and much more prevalent among patients
over 75 years old.
Race and ethnicity Data from the ASSERT observational study
suggest lower rates of subclinical atrial fibrillation
among black and southeast Asian persons
compared to persons of white European
ancestry.
Overall representativeness of this trial The ARTESIA randomized trial had only 36%
female participants, compared to 57.5% in the
ASSERT observational study. This suggests an
under-representation of women. The proportion
of black and native Latin individuals in ARTESIA
are lower than in the overall North American
population, however a large proportion of the
trial enrollment came from Europe. There is a
slight under-representation of patients with a
history of stroke or TIA in ARTESIA compared to
observational studies of subclinical atrial
fibrillation (about 15-20% less prevalent).
4. Table S2: Intention to treat analysis without censoring follow up after AF or SCAF>24 hours

Apixaban Aspirin HR (95% CI) P-Value

(N=2015) N=2015

n (% per year) n (% per year)

Stroke or systemic embolism 67 (0.83) 94 (1.18) 0.70 (0.51-0.96) 0.026

Stroke 66 (0.81) 92 (1.16) 0.70 (0.51-0.97)
Ischemic stroke or unknown type 54 (0.66) 78 (0.98) 0.68 (0.48-0.96)
Hemorrhagic stroke 12 (0.15) 14 (0.17) 0.92 (0.43-1.96)
Stroke with mRS 0-2 38 (0.47) 50 (0.62) 0.75 (0.49-1.14)
Stroke with mRS 3-6 23 (0.28) 40 (0.50) 0.57 (0.34-0.95)
Stroke with mRS missing 5 (0.06) 2 (0.02) 2.46 (0.48-12.68)
Systemic Embolism 1 (0.01) 2 (0.02) 0.50 (0.05-5.51)
Stroke, TIA* or systemic embolism 96 (1.19) 117 (1.48) 0.81 (0.62-1.06)
Stroke, systemic embolism or 190 (2.34) 211 (2.65) 0.88 (0.72-1.07)
Cardiovascular death
Stroke, myocardial infarction, 524 (6.54) 523 (6.64) 0.98 (0.87-1.11)
systemic embolism or death
Myocardial infarction 45 (0.55) 46 (0.57) 0.97 (0.64-1.46)
Death 457 (5.55) 438 (5.39) 1.03 (0.90-1.17)
Cardiovascular death 137 (1.66) 142 (1.75) 0.95 (0.75-1.20)
Major Bleeding (ISTH) 123 (1.54) 90 (1.13) 1.36 (1.04-1.79) 0.027
Fatal bleeding 12 (0.15) 14 (0.17) 0.85 (0.39-1.83)
Symptomatic intracranial 21 (0.26) 24 (0.30) 0.86 (0.48-1.55)
Hemorrhage
GI bleeding 62 (0.77) 37 (0.46) 1.66 (1.10-2.49)
Transfusion required 44 (0.54) 36 (0.45) 1.20 (0.77-1.86)
5. Summary of Serious Adverse Events

Overall Apixaban Aspirin

System organ class Preferred term n (%) n (%) n (%)
Patients randomized N=4012 N=2015 N=1997
Patients with SAE 1622 (40.43) 823 (40.84) 799 (40.01)

Blood and lymphatic system disorders 24 (0.60) 16 (0.79) 8 (0.40)

Anaemia 8 (0.20) 5 (0.25) 3 (0.15)
Febrile neutropenia 1 (0.02) 1 (0.05) 0 (0.00)
Iron deficiency anaemia 6 (0.15) 4 (0.20) 2 (0.10)
Lymphadenopathy 1 (0.02) 1 (0.05) 0 (0.00)
Lymphadenopathy mediastinal 1 (0.02) 0 (0.00) 1 (0.05)
Normochromic anaemia 1 (0.02) 1 (0.05) 0 (0.00)
Normocytic anaemia 1 (0.02) 1 (0.05) 0 (0.00)
Splenic infarction 1 (0.02) 1 (0.05) 0 (0.00)
Thrombocytopenia 2 (0.05) 1 (0.05) 1 (0.05)
Blood loss anaemia 1 (0.02) 1 (0.05) 0 (0.00)
Immune thrombocytopenia 1 (0.02) 0 (0.00) 1 (0.05)
Cardiac disorders 301 (7.50) 151 (7.49) 150 (7.51)
Acute myocardial infarction 5 (0.12) 4 (0.20) 1 (0.05)
Angina pectoris 18 (0.45) 9 (0.45) 9 (0.45)
Angina unstable 18 (0.45) 6 (0.30) 12 (0.60)
Aortic valve incompetence 1 (0.02) 0 (0.00) 1 (0.05)
Aortic valve stenosis 2 (0.05) 1 (0.05) 1 (0.05)
Arrhythmia 1 (0.02) 1 (0.05) 0 (0.00)
Arteriosclerosis coronary artery 2 (0.05) 2 (0.10) 0 (0.00)
Atrial fibrillation 8 (0.20) 3 (0.15) 5 (0.25)
Atrial flutter 10 (0.25) 4 (0.20) 6 (0.30)
Atrial tachycardia 3 (0.07) 0 (0.00) 3 (0.15)
Atrioventricular block 2 (0.05) 0 (0.00) 2 (0.10)
Atrioventricular block complete 1 (0.02) 0 (0.00) 1 (0.05)
Bradycardia 2 (0.05) 2 (0.10) 0 (0.00)
Cardiac amyloidosis 1 (0.02) 0 (0.00) 1 (0.05)
Cardiac arrest 29 (0.72) 15 (0.74) 14 (0.70)
Cardiac failure 27 (0.67) 13 (0.65) 14 (0.70)
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Cardiac failure acute 4 (0.10) 3 (0.15) 1 (0.05)
Cardiac failure chronic 4 (0.10) 1 (0.05) 3 (0.15)
Cardiac failure congestive 16 (0.40) 6 (0.30) 10 (0.50)
Cardiac tamponade 1 (0.02) 0 (0.00) 1 (0.05)
Cardio-respiratory arrest 2 (0.05) 1 (0.05) 1 (0.05)
Cardiogenic shock 5 (0.12) 3 (0.15) 2 (0.10)
Cardiomyopathy 3 (0.07) 2 (0.10) 1 (0.05)
Coronary artery disease 26 (0.65) 11 (0.55) 15 (0.75)
Coronary artery occlusion 1 (0.02) 1 (0.05) 0 (0.00)
Coronary artery stenosis 11 (0.27) 3 (0.15) 8 (0.40)
Mitral valve incompetence 6 (0.15) 5 (0.25) 1 (0.05)
Myocardial infarction 6 (0.15) 3 (0.15) 3 (0.15)
Myocardial ischaemia 1 (0.02) 0 (0.00) 1 (0.05)
Palpitations 1 (0.02) 0 (0.00) 1 (0.05)
Pericardial effusion 4 (0.10) 3 (0.15) 1 (0.05)
Pericarditis 4 (0.10) 2 (0.10) 2 (0.10)
Pulmonary valve stenosis 1 (0.02) 1 (0.05) 0 (0.00)
Supraventricular tachycardia 3 (0.07) 2 (0.10) 1 (0.05)
Tachycardia 1 (0.02) 1 (0.05) 0 (0.00)
Torsade de pointes 1 (0.02) 1 (0.05) 0 (0.00)
Ventricular arrhythmia 1 (0.02) 0 (0.00) 1 (0.05)
Ventricular extrasystoles 4 (0.10) 3 (0.15) 1 (0.05)
Ventricular fibrillation 9 (0.22) 4 (0.20) 5 (0.25)
Ventricular tachycardia 72 (1.79) 39 (1.94) 33 (1.65)
Intracardiac thrombus 2 (0.05) 0 (0.00) 2 (0.10)
Ischaemic cardiomyopathy 4 (0.10) 3 (0.15) 1 (0.05)
Left ventricular dysfunction 1 (0.02) 0 (0.00) 1 (0.05)
Acute coronary syndrome 7 (0.17) 2 (0.10) 5 (0.25)
Cardiac ventricular thrombosis 1 (0.02) 0 (0.00) 1 (0.05)
Dilated cardiomyopathy 1 (0.02) 0 (0.00) 1 (0.05)
Aortic valve disease 1 (0.02) 0 (0.00) 1 (0.05)
Stress cardiomyopathy 1 (0.02) 1 (0.05) 0 (0.00)
Arrhythmic storm 4 (0.10) 2 (0.10) 2 (0.10)
Sinus node dysfunction 7 (0.17) 7 (0.35) 0 (0.00)
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Congenital, familial and genetic 2 (0.05) 2 (0.10) 0 (0.00)
disorders
Gastrointestinal arteriovenous 1 (0.02) 1 (0.05) 0 (0.00)
malformation
Tracheo-oesophageal fistula 1 (0.02) 1 (0.05) 0 (0.00)
Ear and labyrinth disorders 11 (0.27) 5 (0.25) 6 (0.30)
Aural polyp 1 (0.02) 1 (0.05) 0 (0.00)
Ear disorder 1 (0.02) 1 (0.05) 0 (0.00)
Meniere's disease 1 (0.02) 0 (0.00) 1 (0.05)
Vertigo 7 (0.17) 3 (0.15) 4 (0.20)
Vestibular disorder 1 (0.02) 0 (0.00) 1 (0.05)
Endocrine disorders 3 (0.07) 1 (0.05) 2 (0.10)
Goitre 1 (0.02) 1 (0.05) 0 (0.00)
Hyperparathyroidism primary 1 (0.02) 0 (0.00) 1 (0.05)
Hypothyroidism 1 (0.02) 0 (0.00) 1 (0.05)
Eye disorders 9 (0.22) 3 (0.15) 6 (0.30)
Amaurosis fugax 1 (0.02) 1 (0.05) 0 (0.00)
Blindness 1 (0.02) 0 (0.00) 1 (0.05)
Cataract 1 (0.02) 1 (0.05) 0 (0.00)
Diplopia 1 (0.02) 0 (0.00) 1 (0.05)
Ocular hyperaemia 1 (0.02) 1 (0.05) 0 (0.00)
Retinal degeneration 1 (0.02) 0 (0.00) 1 (0.05)
Retinal detachment 1 (0.02) 0 (0.00) 1 (0.05)
Endocrine ophthalmopathy 1 (0.02) 0 (0.00) 1 (0.05)
Scleral degeneration 1 (0.02) 0 (0.00) 1 (0.05)
Gastrointestinal disorders 101 (2.52) 45 (2.23) 56 (2.80)
Abdominal distension 1 (0.02) 1 (0.05) 0 (0.00)
Abdominal pain 5 (0.12) 4 (0.20) 1 (0.05)
Abdominal pain upper 2 (0.05) 1 (0.05) 1 (0.05)
Colitis 1 (0.02) 0 (0.00) 1 (0.05)
Colitis ischaemic 2 (0.05) 0 (0.00) 2 (0.10)
Constipation 4 (0.10) 1 (0.05) 3 (0.15)
Crohn's disease 1 (0.02) 0 (0.00) 1 (0.05)
Diarrhoea 7 (0.17) 2 (0.10) 5 (0.25)
Diverticulum 1 (0.02) 0 (0.00) 1 (0.05)
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Duodenal ulcer 1 (0.02) 1 (0.05) 0 (0.00)
Dyspepsia 2 (0.05) 1 (0.05) 1 (0.05)
Dysphagia 1 (0.02) 1 (0.05) 0 (0.00)
Enteritis 1 (0.02) 0 (0.00) 1 (0.05)
Food poisoning 1 (0.02) 0 (0.00) 1 (0.05)
Gastric ulcer 4 (0.10) 1 (0.05) 3 (0.15)
Gastric ulcer haemorrhage 1 (0.02) 0 (0.00) 1 (0.05)
Gastric ulcer perforation 2 (0.05) 0 (0.00) 2 (0.10)
Gastritis 2 (0.05) 1 (0.05) 1 (0.05)
Gastrooesophageal reflux 1 (0.02) 0 (0.00) 1 (0.05)
disease
Gastrointestinal haemorrhage 2 (0.05) 0 (0.00) 2 (0.10)
Hiatus hernia 1 (0.02) 1 (0.05) 0 (0.00)
Ileus 5 (0.12) 3 (0.15) 2 (0.10)
Ileus paralytic 1 (0.02) 0 (0.00) 1 (0.05)
Incarcerated inguinal hernia 1 (0.02) 0 (0.00) 1 (0.05)
Inguinal hernia 5 (0.12) 3 (0.15) 2 (0.10)
Intestinal infarction 1 (0.02) 1 (0.05) 0 (0.00)
Intestinal ischaemia 2 (0.05) 1 (0.05) 1 (0.05)
Intestinal obstruction 12 (0.30) 7 (0.35) 5 (0.25)
Intestinal perforation 1 (0.02) 0 (0.00) 1 (0.05)
Intestinal pseudo-obstruction 3 (0.07) 1 (0.05) 2 (0.10)
Pancreatic disorder 1 (0.02) 0 (0.00) 1 (0.05)
Pancreatitis 10 (0.25) 4 (0.20) 6 (0.30)
Pancreatitis acute 2 (0.05) 1 (0.05) 1 (0.05)
Proctitis 1 (0.02) 1 (0.05) 0 (0.00)
Small intestinal obstruction 7 (0.17) 6 (0.30) 1 (0.05)
Tongue oedema 1 (0.02) 0 (0.00) 1 (0.05)
Vomiting 4 (0.10) 1 (0.05) 3 (0.15)
Alcoholic pancreatitis 1 (0.02) 1 (0.05) 0 (0.00)
Intestinal mass 2 (0.05) 2 (0.10) 0 (0.00)
Diverticular perforation 1 (0.02) 0 (0.00) 1 (0.05)
Erosive oesophagitis 1 (0.02) 0 (0.00) 1 (0.05)
Coeliac artery stenosis 1 (0.02) 1 (0.05) 0 (0.00)
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Gastrointestinal vascular 1 (0.02) 1 (0.05) 0 (0.00)
malformation
Abdominal incarcerated hernia 1 (0.02) 1 (0.05) 0 (0.00)
Ampullary polyp 1 (0.02) 1 (0.05) 0 (0.00)
Obstructive pancreatitis 3 (0.07) 1 (0.05) 2 (0.10)
General disorders and administration 269 (6.70) 140 (6.95) 129 (6.46)
site conditions
Asthenia 17 (0.42) 3 (0.15) 14 (0.70)
Chest discomfort 2 (0.05) 2 (0.10) 0 (0.00)
Chest pain 35 (0.87) 17 (0.84) 18 (0.90)
Death 124 (3.09) 67 (3.33) 57 (2.85)
Drowning 2 (0.05) 2 (0.10) 0 (0.00)
Drug withdrawal syndrome 1 (0.02) 0 (0.00) 1 (0.05)
Gait disturbance 2 (0.05) 0 (0.00) 2 (0.10)
Hyperpyrexia 1 (0.02) 0 (0.00) 1 (0.05)
Incarcerated hernia 1 (0.02) 1 (0.05) 0 (0.00)
Malaise 2 (0.05) 0 (0.00) 2 (0.10)
Mass 2 (0.05) 2 (0.10) 0 (0.00)
Oedema peripheral 3 (0.07) 3 (0.15) 0 (0.00)
Pain 2 (0.05) 0 (0.00) 2 (0.10)
Polyserositis 1 (0.02) 1 (0.05) 0 (0.00)
Pyrexia 4 (0.10) 3 (0.15) 1 (0.05)
Sudden death 12 (0.30) 7 (0.35) 5 (0.25)
Sudden cardiac death 18 (0.45) 8 (0.40) 10 (0.50)
General physical health 18 (0.45) 11 (0.55) 7 (0.35)
deterioration
Cardiac death 5 (0.12) 4 (0.20) 1 (0.05)
Systemic inflammatory 1 (0.02) 1 (0.05) 0 (0.00)
response syndrome
Inflammation 1 (0.02) 1 (0.05) 0 (0.00)
Polyp 2 (0.05) 1 (0.05) 1 (0.05)
Adverse drug reaction 4 (0.10) 1 (0.05) 3 (0.15)
Non-cardiac chest pain 7 (0.17) 4 (0.20) 3 (0.15)
Stent-graft endoleak 1 (0.02) 1 (0.05) 0 (0.00)
Multiple organ dysfunction 8 (0.20) 2 (0.10) 6 (0.30)
syndrome
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Hepatobiliary disorders 53 (1.32) 29 (1.44) 24 (1.20)
Acute hepatic failure 2 (0.05) 1 (0.05) 1 (0.05)
Bile duct stone 8 (0.20) 5 (0.25) 3 (0.15)
Biliary colic 1 (0.02) 0 (0.00) 1 (0.05)
Cholangitis 5 (0.12) 4 (0.20) 1 (0.05)
Cholangitis acute 1 (0.02) 1 (0.05) 0 (0.00)
Cholecystitis 8 (0.20) 4 (0.20) 4 (0.20)
Cholecystitis acute 10 (0.25) 5 (0.25) 5 (0.25)
Cholelithiasis 10 (0.25) 4 (0.20) 6 (0.30)
Hepatic cirrhosis 6 (0.15) 4 (0.20) 2 (0.10)
Hepatic failure 2 (0.05) 2 (0.10) 0 (0.00)
Hepatic function abnormal 1 (0.02) 0 (0.00) 1 (0.05)
Hepatic steatosis 1 (0.02) 0 (0.00) 1 (0.05)
Jaundice 2 (0.05) 2 (0.10) 0 (0.00)
Portal vein thrombosis 1 (0.02) 0 (0.00) 1 (0.05)
Hypertransaminasaemia 1 (0.02) 0 (0.00) 1 (0.05)
Gallbladder rupture 1 (0.02) 0 (0.00) 1 (0.05)
Immune system disorders 4 (0.10) 3 (0.15) 1 (0.05)
Drug hypersensitivity 1 (0.02) 1 (0.05) 0 (0.00)
Hypersensitivity 1 (0.02) 1 (0.05) 0 (0.00)
Sarcoidosis 1 (0.02) 0 (0.00) 1 (0.05)
Eosinophilic granulomatosis 1 (0.02) 1 (0.05) 0 (0.00)
with polyangiitis
Infections and infestations 478 (11.91) 258 (12.80) 220 (11.02)
Abscess 1 (0.02) 1 (0.05) 0 (0.00)
Appendicitis 4 (0.10) 3 (0.15) 1 (0.05)
Appendicitis perforated 1 (0.02) 0 (0.00) 1 (0.05)
Bacteraemia 1 (0.02) 1 (0.05) 0 (0.00)
Bronchitis 7 (0.17) 6 (0.30) 1 (0.05)
Cellulitis 18 (0.45) 10 (0.50) 8 (0.40)
Clostridium difficile colitis 4 (0.10) 1 (0.05) 3 (0.15)
Cystitis 5 (0.12) 4 (0.20) 1 (0.05)
Diverticulitis 7 (0.17) 5 (0.25) 2 (0.10)
Diverticulitis intestinal 1 (0.02) 0 (0.00) 1 (0.05)
haemorrhagic
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Ear infection 1 (0.02) 1 (0.05) 0 (0.00)
Endocarditis 10 (0.25) 6 (0.30) 4 (0.20)
Enterococcal bacteraemia 1 (0.02) 0 (0.00) 1 (0.05)
Epiglottitis 2 (0.05) 1 (0.05) 1 (0.05)
Erysipelas 4 (0.10) 1 (0.05) 3 (0.15)
Escherichia sepsis 1 (0.02) 0 (0.00) 1 (0.05)
Fournier's gangrene 1 (0.02) 0 (0.00) 1 (0.05)
Fungaemia 1 (0.02) 0 (0.00) 1 (0.05)
Gangrene 3 (0.07) 1 (0.05) 2 (0.10)
Gastroenteritis 5 (0.12) 2 (0.10) 3 (0.15)
Gastroenteritis viral 1 (0.02) 1 (0.05) 0 (0.00)
Hepatitis A 1 (0.02) 0 (0.00) 1 (0.05)
Herpes zoster 1 (0.02) 0 (0.00) 1 (0.05)
Infection 7 (0.17) 4 (0.20) 3 (0.15)
Influenza 5 (0.12) 3 (0.15) 2 (0.10)
Liver abscess 1 (0.02) 0 (0.00) 1 (0.05)
Localised infection 2 (0.05) 1 (0.05) 1 (0.05)
Lower respiratory tract 4 (0.10) 1 (0.05) 3 (0.15)
infection
Meningitis pneumococcal 1 (0.02) 1 (0.05) 0 (0.00)
Nasopharyngitis 1 (0.02) 1 (0.05) 0 (0.00)
Necrotising fasciitis 1 (0.02) 1 (0.05) 0 (0.00)
Orchitis 1 (0.02) 1 (0.05) 0 (0.00)
Osteomyelitis 5 (0.12) 2 (0.10) 3 (0.15)
Osteomyelitis chronic 1 (0.02) 1 (0.05) 0 (0.00)
Peritonitis 1 (0.02) 0 (0.00) 1 (0.05)
Pneumonia 148 (3.69) 80 (3.97) 68 (3.41)
Pneumonia aspiration 12 (0.30) 10 (0.50) 2 (0.10)
Pneumonia influenzal 1 (0.02) 0 (0.00) 1 (0.05)
Pneumonia legionella 1 (0.02) 0 (0.00) 1 (0.05)
Postoperative wound infection 2 (0.05) 0 (0.00) 2 (0.10)
Pyelonephritis 5 (0.12) 1 (0.05) 4 (0.20)
Pyelonephritis acute 4 (0.10) 2 (0.10) 2 (0.10)
Renal abscess 1 (0.02) 1 (0.05) 0 (0.00)
Sepsis 43 (1.07) 22 (1.09) 21 (1.05)
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Septic shock 14 (0.35) 8 (0.40) 6 (0.30)
Upper respiratory tract 4 (0.10) 1 (0.05) 3 (0.15)
infection
Urinary tract infection 52 (1.30) 24 (1.19) 28 (1.40)
Vestibular neuronitis 2 (0.05) 1 (0.05) 1 (0.05)
Viral infection 2 (0.05) 1 (0.05) 1 (0.05)
Viral upper respiratory tract 2 (0.05) 2 (0.10) 0 (0.00)
infection
Wound infection 1 (0.02) 1 (0.05) 0 (0.00)
Urosepsis 18 (0.45) 13 (0.65) 5 (0.25)
Streptococcal sepsis 5 (0.12) 3 (0.15) 2 (0.10)
Abscess limb 1 (0.02) 1 (0.05) 0 (0.00)
Staphylococcal bacteraemia 4 (0.10) 0 (0.00) 4 (0.20)
Streptococcal bacteraemia 2 (0.05) 0 (0.00) 2 (0.10)
Gastric ulcer helicobacter 1 (0.02) 0 (0.00) 1 (0.05)
Burn infection 1 (0.02) 1 (0.05) 0 (0.00)
Pulmonary sepsis 1 (0.02) 0 (0.00) 1 (0.05)
Escherichia urinary tract 1 (0.02) 0 (0.00) 1 (0.05)
infection
Candida sepsis 2 (0.05) 0 (0.00) 2 (0.10)
Arthritis bacterial 2 (0.05) 1 (0.05) 1 (0.05)
Bacterial sepsis 1 (0.02) 0 (0.00) 1 (0.05)
Enterococcal sepsis 1 (0.02) 0 (0.00) 1 (0.05)
Clostridium difficile infection 3 (0.07) 2 (0.10) 1 (0.05)
Escherichia bacteraemia 2 (0.05) 1 (0.05) 1 (0.05)
Staphylococcal sepsis 1 (0.02) 1 (0.05) 0 (0.00)
Infective exacerbation of 1 (0.02) 0 (0.00) 1 (0.05)
chronic obstructive airways
disease
West Nile viral infection 1 (0.02) 0 (0.00) 1 (0.05)
Cardiac valve vegetation 1 (0.02) 1 (0.05) 0 (0.00)
Biliary sepsis 1 (0.02) 0 (0.00) 1 (0.05)
Abdominal sepsis 1 (0.02) 1 (0.05) 0 (0.00)
Staphylococcal infection 1 (0.02) 1 (0.05) 0 (0.00)
Pneumonia bacterial 3 (0.07) 1 (0.05) 2 (0.10)
Arthritis infective 2 (0.05) 2 (0.10) 0 (0.00)
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Enterococcal infection 1 (0.02) 1 (0.05) 0 (0.00)
Streptococcal infection 1 (0.02) 1 (0.05) 0 (0.00)
Respiratory syncytial virus 2 (0.05) 1 (0.05) 1 (0.05)
infection
Respiratory tract infection 5 (0.12) 5 (0.25) 0 (0.00)
Device related infection 1 (0.02) 0 (0.00) 1 (0.05)
Dermo-hypodermitis 1 (0.02) 1 (0.05) 0 (0.00)
Septic arthritis streptococcal 1 (0.02) 0 (0.00) 1 (0.05)
Perihepatic abscess 1 (0.02) 1 (0.05) 0 (0.00)
Respiratory syncytial virus 1 (0.02) 0 (0.00) 1 (0.05)
bronchitis
Meningoencephalitis viral 1 (0.02) 0 (0.00) 1 (0.05)
Infective aortitis 2 (0.05) 1 (0.05) 1 (0.05)
COVID-19 64 (1.60) 35 (1.74) 29 (1.45)
Diverticulitis intestinal 1 (0.02) 0 (0.00) 1 (0.05)
perforated
COVID-19 pneumonia 35 (0.87) 16 (0.79) 19 (0.95)
Suspected COVID-19 1 (0.02) 0 (0.00) 1 (0.05)
Varicella encephalitis 1 (0.02) 1 (0.05) 0 (0.00)
Injury, poisoning and procedural 222 (5.53) 111 (5.51) 111 (5.56)
complications
Accident 3 (0.07) 1 (0.05) 2 (0.10)
Accidental overdose 2 (0.05) 1 (0.05) 1 (0.05)
Alcohol poisoning 2 (0.05) 1 (0.05) 1 (0.05)
Animal bite 1 (0.02) 1 (0.05) 0 (0.00)
Ankle fracture 5 (0.12) 1 (0.05) 4 (0.20)
Chillblains 1 (0.02) 0 (0.00) 1 (0.05)
Clavicle fracture 2 (0.05) 1 (0.05) 1 (0.05)
Concussion 1 (0.02) 0 (0.00) 1 (0.05)
Fall 45 (1.12) 24 (1.19) 21 (1.05)
Fat embolism 1 (0.02) 1 (0.05) 0 (0.00)
Femoral neck fracture 11 (0.27) 7 (0.35) 4 (0.20)
Femur fracture 21 (0.52) 7 (0.35) 14 (0.70)
Foot fracture 5 (0.12) 2 (0.10) 3 (0.15)
Fractured sacrum 1 (0.02) 0 (0.00) 1 (0.05)
Hand fracture 2 (0.05) 0 (0.00) 2 (0.10)
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Head injury 5 (0.12) 1 (0.05) 4 (0.20)
Heat exhaustion 1 (0.02) 1 (0.05) 0 (0.00)
Hip fracture 27 (0.67) 19 (0.94) 8 (0.40)
Humerus fracture 4 (0.10) 0 (0.00) 4 (0.20)
Incisional hernia 1 (0.02) 0 (0.00) 1 (0.05)
Injury 1 (0.02) 1 (0.05) 0 (0.00)
Intentional overdose 1 (0.02) 1 (0.05) 0 (0.00)
Jaw fracture 1 (0.02) 0 (0.00) 1 (0.05)
Joint dislocation 3 (0.07) 1 (0.05) 2 (0.10)
Multiple fractures 3 (0.07) 1 (0.05) 2 (0.10)
Multiple injuries 1 (0.02) 0 (0.00) 1 (0.05)
Muscle rupture 1 (0.02) 1 (0.05) 0 (0.00)
Overdose 1 (0.02) 1 (0.05) 0 (0.00)
Patella fracture 1 (0.02) 0 (0.00) 1 (0.05)
Pneumothorax traumatic 1 (0.02) 0 (0.00) 1 (0.05)
Radius fracture 4 (0.10) 1 (0.05) 3 (0.15)
Rib fracture 15 (0.37) 6 (0.30) 9 (0.45)
Road traffic accident 4 (0.10) 3 (0.15) 1 (0.05)
Seroma 1 (0.02) 0 (0.00) 1 (0.05)
Spinal compression fracture 2 (0.05) 1 (0.05) 1 (0.05)
Spinal fracture 2 (0.05) 2 (0.10) 0 (0.00)
Splenic rupture 1 (0.02) 0 (0.00) 1 (0.05)
Subdural haematoma 2 (0.05) 0 (0.00) 2 (0.10)
Tendon rupture 1 (0.02) 1 (0.05) 0 (0.00)
Tibia fracture 3 (0.07) 2 (0.10) 1 (0.05)
Ulna fracture 1 (0.02) 1 (0.05) 0 (0.00)
Wrist fracture 3 (0.07) 2 (0.10) 1 (0.05)
Vascular pseudoaneurysm 2 (0.05) 1 (0.05) 1 (0.05)
Vascular graft occlusion 1 (0.02) 1 (0.05) 0 (0.00)
Shoulder fracture 1 (0.02) 1 (0.05) 0 (0.00)
Traumatic fracture 1 (0.02) 0 (0.00) 1 (0.05)
Cervical vertebral fracture 4 (0.10) 2 (0.10) 2 (0.10)
Lumbar vertebral fracture 3 (0.07) 1 (0.05) 2 (0.10)
Thoracic vertebral fracture 1 (0.02) 1 (0.05) 0 (0.00)
Contusion 1 (0.02) 1 (0.05) 0 (0.00)
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Prescribed overdose 1 (0.02) 1 (0.05) 0 (0.00)
Post procedural complication 1 (0.02) 0 (0.00) 1 (0.05)
Skin laceration 1 (0.02) 0 (0.00) 1 (0.05)
Joint injury 2 (0.05) 1 (0.05) 1 (0.05)
Pelvic fracture 8 (0.20) 6 (0.30) 2 (0.10)
Iatrogenic injury 1 (0.02) 0 (0.00) 1 (0.05)
Poisoning 1 (0.02) 0 (0.00) 1 (0.05)
Skull fracture 1 (0.02) 0 (0.00) 1 (0.05)
Traumatic intracranial 3 (0.07) 1 (0.05) 2 (0.10)
haemorrhage
Upper limb fracture 2 (0.05) 1 (0.05) 1 (0.05)
Incorrect dose administered 1 (0.02) 0 (0.00) 1 (0.05)
Post-traumatic pain 1 (0.02) 1 (0.05) 0 (0.00)
Avulsion fracture 1 (0.02) 1 (0.05) 0 (0.00)
Periprosthetic fracture 3 (0.07) 2 (0.10) 1 (0.05)
Toxicity to various agents 2 (0.05) 0 (0.00) 2 (0.10)
Craniocerebral injury 4 (0.10) 2 (0.10) 2 (0.10)
Urinary tract stoma 1 (0.02) 1 (0.05) 0 (0.00)
complication
Contraindicated product 1 (0.02) 1 (0.05) 0 (0.00)
administered
Lisfranc fracture 1 (0.02) 1 (0.05) 0 (0.00)
Foreign body in gastrointestinal 1 (0.02) 1 (0.05) 0 (0.00)
tract
Product administration error 2 (0.05) 1 (0.05) 1 (0.05)
Investigations 59 (1.47) 30 (1.49) 29 (1.45)
Alanine aminotransferase 1 (0.02) 1 (0.05) 0 (0.00)
increased
Amylase increased 1 (0.02) 0 (0.00) 1 (0.05)
Antimicrobial susceptibility test 1 (0.02) 0 (0.00) 1 (0.05)
resistant
Biopsy 1 (0.02) 0 (0.00) 1 (0.05)
Blood creatinine abnormal 1 (0.02) 1 (0.05) 0 (0.00)
Blood creatinine increased 3 (0.07) 2 (0.10) 1 (0.05)
Blood sodium decreased 1 (0.02) 0 (0.00) 1 (0.05)
Creatinine renal clearance 2 (0.05) 1 (0.05) 1 (0.05)
decreased
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Endoscopic retrograde 1 (0.02) 0 (0.00) 1 (0.05)
cholangiopancreatography
Haemoglobin decreased 2 (0.05) 0 (0.00) 2 (0.10)
Weight decreased 3 (0.07) 2 (0.10) 1 (0.05)
Free prostate-specific antigen 1 (0.02) 0 (0.00) 1 (0.05)
increased
Troponin increased 2 (0.05) 1 (0.05) 1 (0.05)
Investigation abnormal 1 (0.02) 0 (0.00) 1 (0.05)
Angiogram 1 (0.02) 1 (0.05) 0 (0.00)
Creatinine renal clearance 1 (0.02) 1 (0.05) 0 (0.00)
abnormal
Influenza A virus test positive 1 (0.02) 1 (0.05) 0 (0.00)
SARS-CoV-2 test positive 30 (0.75) 15 (0.74) 15 (0.75)
SARS-CoV-2 test negative 1 (0.02) 0 (0.00) 1 (0.05)
SARS-CoV-2 antibody test 2 (0.05) 2 (0.10) 0 (0.00)
positive
SARS-CoV-2 test false positive 1 (0.02) 1 (0.05) 0 (0.00)
Myocardial strain imaging 1 (0.02) 1 (0.05) 0 (0.00)
Metabolism and nutrition disorders 54 (1.35) 27 (1.34) 27 (1.35)
Cachexia 1 (0.02) 1 (0.05) 0 (0.00)
Dehydration 10 (0.25) 5 (0.25) 5 (0.25)
Diabetic ketoacidosis 1 (0.02) 0 (0.00) 1 (0.05)
Failure to thrive 3 (0.07) 0 (0.00) 3 (0.15)
Gout 1 (0.02) 0 (0.00) 1 (0.05)
Hyperglycaemia 1 (0.02) 1 (0.05) 0 (0.00)
Hyperkalaemia 6 (0.15) 3 (0.15) 3 (0.15)
Hypernatraemia 1 (0.02) 1 (0.05) 0 (0.00)
Hypervolaemia 1 (0.02) 1 (0.05) 0 (0.00)
Hypoglycaemia 3 (0.07) 1 (0.05) 2 (0.10)
Hypokalaemia 2 (0.05) 0 (0.00) 2 (0.10)
Hyponatraemia 9 (0.22) 6 (0.30) 3 (0.15)
Metabolic acidosis 1 (0.02) 1 (0.05) 0 (0.00)
Obesity 1 (0.02) 0 (0.00) 1 (0.05)
Malnutrition 3 (0.07) 2 (0.10) 1 (0.05)
Mineral deficiency 1 (0.02) 1 (0.05) 0 (0.00)
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Hyperglycaemic hyperosmolar 3 (0.07) 3 (0.15) 0 (0.00)
nonketotic syndrome
Diabetic metabolic 1 (0.02) 1 (0.05) 0 (0.00)
decompensation
Adult failure to thrive 8 (0.20) 3 (0.15) 5 (0.25)
Musculoskeletal and connective tissue 61 (1.52) 37 (1.84) 24 (1.20)
disorders
Arthralgia 1 (0.02) 1 (0.05) 0 (0.00)
Arthritis 2 (0.05) 1 (0.05) 1 (0.05)
Back pain 9 (0.22) 4 (0.20) 5 (0.25)
Bursitis 1 (0.02) 0 (0.00) 1 (0.05)
Cervical spinal stenosis 1 (0.02) 1 (0.05) 0 (0.00)
Muscular weakness 2 (0.05) 2 (0.10) 0 (0.00)
Musculoskeletal pain 1 (0.02) 1 (0.05) 0 (0.00)
Myalgia 1 (0.02) 1 (0.05) 0 (0.00)
Neck pain 1 (0.02) 1 (0.05) 0 (0.00)
Osteitis 2 (0.05) 1 (0.05) 1 (0.05)
Osteoarthritis 18 (0.45) 10 (0.50) 8 (0.40)
Osteonecrosis 1 (0.02) 0 (0.00) 1 (0.05)
Osteoporotic fracture 1 (0.02) 1 (0.05) 0 (0.00)
Pain in extremity 2 (0.05) 2 (0.10) 0 (0.00)
Polyarthritis 1 (0.02) 1 (0.05) 0 (0.00)
Polymyalgia rheumatica 2 (0.05) 1 (0.05) 1 (0.05)
Polymyositis 1 (0.02) 0 (0.00) 1 (0.05)
Rhabdomyolysis 1 (0.02) 1 (0.05) 0 (0.00)
Rheumatoid arthritis 1 (0.02) 1 (0.05) 0 (0.00)
Rotator cuff syndrome 2 (0.05) 1 (0.05) 1 (0.05)
Sacroiliitis 1 (0.02) 0 (0.00) 1 (0.05)
Intervertebral disc protrusion 3 (0.07) 2 (0.10) 1 (0.05)
Musculoskeletal chest pain 3 (0.07) 2 (0.10) 1 (0.05)
Chondrocalcinosis 1 (0.02) 1 (0.05) 0 (0.00)
Sarcopenia 1 (0.02) 1 (0.05) 0 (0.00)
Soft tissue necrosis 1 (0.02) 0 (0.00) 1 (0.05)
Neoplasms benign, malignant and 277 (6.90) 144 (7.15) 133 (6.66)
unspecified (incl cysts and polyps)
Acute myeloid leukaemia 1 (0.02) 0 (0.00) 1 (0.05)
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Acute promyelocytic leukaemia 1 (0.02) 1 (0.05) 0 (0.00)
Adenocarcinoma gastric 1 (0.02) 1 (0.05) 0 (0.00)
Adenocarcinoma of colon 2 (0.05) 1 (0.05) 1 (0.05)
B-cell lymphoma 2 (0.05) 1 (0.05) 1 (0.05)
Basal cell carcinoma 13 (0.32) 7 (0.35) 6 (0.30)
Benign lung neoplasm 1 (0.02) 1 (0.05) 0 (0.00)
Bladder cancer 10 (0.25) 5 (0.25) 5 (0.25)
Bladder cancer recurrent 1 (0.02) 0 (0.00) 1 (0.05)
Bladder transitional cell 5 (0.12) 3 (0.15) 2 (0.10)
carcinoma
Brain neoplasm malignant 1 (0.02) 1 (0.05) 0 (0.00)
Breast cancer 13 (0.32) 6 (0.30) 7 (0.35)
Bronchial carcinoma 3 (0.07) 2 (0.10) 1 (0.05)
Carcinoid tumour pulmonary 1 (0.02) 0 (0.00) 1 (0.05)
Central nervous system 1 (0.02) 0 (0.00) 1 (0.05)
neoplasm
Cholangiocarcinoma 2 (0.05) 1 (0.05) 1 (0.05)
Chronic lymphocytic leukaemia 3 (0.07) 1 (0.05) 2 (0.10)
Colon cancer 12 (0.30) 8 (0.40) 4 (0.20)
Colon cancer stage III 1 (0.02) 0 (0.00) 1 (0.05)
Cutaneous T-cell lymphoma 1 (0.02) 1 (0.05) 0 (0.00)
Diffuse large B-cell lymphoma 2 (0.05) 1 (0.05) 1 (0.05)
Gastric cancer 5 (0.12) 4 (0.20) 1 (0.05)
Gastrointestinal carcinoma 3 (0.07) 2 (0.10) 1 (0.05)
Glioblastoma 2 (0.05) 1 (0.05) 1 (0.05)
Hepatic neoplasm 1 (0.02) 0 (0.00) 1 (0.05)
Laryngeal squamous cell 2 (0.05) 0 (0.00) 2 (0.10)
carcinoma
Leukaemia 1 (0.02) 1 (0.05) 0 (0.00)
Lung adenocarcinoma 3 (0.07) 1 (0.05) 2 (0.10)
Lung carcinoma cell type 2 (0.05) 2 (0.10) 0 (0.00)
unspecified recurrent
Lymphoma 2 (0.05) 1 (0.05) 1 (0.05)
Malignant fibrous histiocytoma 1 (0.02) 1 (0.05) 0 (0.00)
Malignant melanoma 9 (0.22) 5 (0.25) 4 (0.20)
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Malignant neoplasm of ampulla 1 (0.02) 0 (0.00) 1 (0.05)
of Vater
Meningioma 2 (0.05) 2 (0.10) 0 (0.00)
Metastases to liver 2 (0.05) 2 (0.10) 0 (0.00)
Myelodysplastic syndrome 3 (0.07) 3 (0.15) 0 (0.00)
Myelofibrosis 1 (0.02) 0 (0.00) 1 (0.05)
Myeloid leukaemia 1 (0.02) 1 (0.05) 0 (0.00)
Neoplasm 3 (0.07) 2 (0.10) 1 (0.05)
Neoplasm malignant 9 (0.22) 5 (0.25) 4 (0.20)
Nephroblastoma 1 (0.02) 0 (0.00) 1 (0.05)
Non-small cell lung cancer 1 (0.02) 0 (0.00) 1 (0.05)
stage I
Non-small cell lung cancer 1 (0.02) 1 (0.05) 0 (0.00)
stage III
Non-Hodgkin's lymphoma 1 (0.02) 0 (0.00) 1 (0.05)
Non-Hodgkin's lymphoma 1 (0.02) 0 (0.00) 1 (0.05)
stage IV
Oesophageal adenocarcinoma 1 (0.02) 1 (0.05) 0 (0.00)
Oesophageal carcinoma 4 (0.10) 2 (0.10) 2 (0.10)
Oropharyngeal cancer 1 (0.02) 1 (0.05) 0 (0.00)
Oropharyngeal squamous cell 1 (0.02) 0 (0.00) 1 (0.05)
carcinoma
Ovarian cancer 4 (0.10) 2 (0.10) 2 (0.10)
Pancreatic carcinoma 8 (0.20) 6 (0.30) 2 (0.10)
Pancreatic carcinoma 3 (0.07) 0 (0.00) 3 (0.15)
metastatic
Plasma cell myeloma 4 (0.10) 3 (0.15) 1 (0.05)
Prostate cancer metastatic 5 (0.12) 3 (0.15) 2 (0.10)
Prostate cancer recurrent 1 (0.02) 1 (0.05) 0 (0.00)
Prostatic adenoma 1 (0.02) 0 (0.00) 1 (0.05)
Rectal cancer 1 (0.02) 1 (0.05) 0 (0.00)
Rectosigmoid cancer 1 (0.02) 1 (0.05) 0 (0.00)
Renal cancer 6 (0.15) 3 (0.15) 3 (0.15)
Skin cancer 7 (0.17) 2 (0.10) 5 (0.25)
Small cell lung cancer 2 (0.05) 1 (0.05) 1 (0.05)
Squamous cell carcinoma 5 (0.12) 1 (0.05) 4 (0.20)
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Squamous cell carcinoma of 3 (0.07) 0 (0.00) 3 (0.15)
skin
Throat cancer 1 (0.02) 1 (0.05) 0 (0.00)
Tongue neoplasm malignant 2 (0.05) 1 (0.05) 1 (0.05)
stage unspecified
Transitional cell cancer of the 1 (0.02) 0 (0.00) 1 (0.05)
renal pelvis and ureter
Transitional cell carcinoma 1 (0.02) 0 (0.00) 1 (0.05)
Ureteric cancer 1 (0.02) 1 (0.05) 0 (0.00)
Uterine cancer 2 (0.05) 0 (0.00) 2 (0.10)
Lung cancer metastatic 5 (0.12) 3 (0.15) 2 (0.10)
Renal cancer metastatic 2 (0.05) 0 (0.00) 2 (0.10)
Gastrointestinal tract adenoma 2 (0.05) 2 (0.10) 0 (0.00)
Metastases to peritoneum 2 (0.05) 1 (0.05) 1 (0.05)
Colorectal adenocarcinoma 1 (0.02) 1 (0.05) 0 (0.00)
Adenocarcinoma pancreas 1 (0.02) 0 (0.00) 1 (0.05)
Gastrointestinal cancer 1 (0.02) 0 (0.00) 1 (0.05)
metastatic
Brain cancer metastatic 3 (0.07) 1 (0.05) 2 (0.10)
Oesophageal cancer metastatic 2 (0.05) 0 (0.00) 2 (0.10)
Thyroid cancer metastatic 2 (0.05) 2 (0.10) 0 (0.00)
Hepatic cancer metastatic 2 (0.05) 2 (0.10) 0 (0.00)
Breast cancer metastatic 2 (0.05) 2 (0.10) 0 (0.00)
Colon cancer metastatic 2 (0.05) 1 (0.05) 1 (0.05)
Lung neoplasm malignant 30 (0.75) 15 (0.74) 15 (0.75)
Small cell lung cancer 1 (0.02) 1 (0.05) 0 (0.00)
metastatic
Prostate cancer 19 (0.47) 7 (0.35) 12 (0.60)
Brain neoplasm 2 (0.05) 0 (0.00) 2 (0.10)
Metastatic neoplasm 1 (0.02) 1 (0.05) 0 (0.00)
Colorectal cancer 3 (0.07) 1 (0.05) 2 (0.10)
Renal neoplasm 1 (0.02) 0 (0.00) 1 (0.05)
Non-small cell lung cancer 2 (0.05) 2 (0.10) 0 (0.00)
Penile neoplasm 1 (0.02) 1 (0.05) 0 (0.00)
Metastatic squamous cell 1 (0.02) 1 (0.05) 0 (0.00)
carcinoma
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Non-Hodgkin's lymphoma 1 (0.02) 1 (0.05) 0 (0.00)
unspecified histology indolent
Bladder transitional cell 1 (0.02) 0 (0.00) 1 (0.05)
carcinoma stage IV
Renal cell carcinoma 3 (0.07) 3 (0.15) 0 (0.00)
Metastatic uterine cancer 1 (0.02) 0 (0.00) 1 (0.05)
Adenosquamous cell carcinoma 1 (0.02) 1 (0.05) 0 (0.00)
Malignant neoplasm of 3 (0.07) 0 (0.00) 3 (0.15)
unknown primary site
Desmoplastic mesothelioma 1 (0.02) 0 (0.00) 1 (0.05)
Hepatic cancer 1 (0.02) 0 (0.00) 1 (0.05)
Invasive ductal breast 1 (0.02) 1 (0.05) 0 (0.00)
carcinoma
Adrenal gland cancer 1 (0.02) 0 (0.00) 1 (0.05)
Mucoepidermoid carcinoma of 1 (0.02) 1 (0.05) 0 (0.00)
salivary gland
Invasive breast carcinoma 1 (0.02) 0 (0.00) 1 (0.05)
Myeloproliferative neoplasm 1 (0.02) 0 (0.00) 1 (0.05)
Epiglottic cancer 1 (0.02) 1 (0.05) 0 (0.00)
Nervous system disorders 146 (3.64) 69 (3.42) 77 (3.86)
Altered state of consciousness 1 (0.02) 1 (0.05) 0 (0.00)
Amyotrophic lateral sclerosis 4 (0.10) 2 (0.10) 2 (0.10)
Carotid artery stenosis 2 (0.05) 1 (0.05) 1 (0.05)
Cauda equina syndrome 1 (0.02) 0 (0.00) 1 (0.05)
Cerebral haemorrhage 2 (0.05) 1 (0.05) 1 (0.05)
Cerebrovascular accident 3 (0.07) 2 (0.10) 1 (0.05)
Cerebrovascular disorder 1 (0.02) 1 (0.05) 0 (0.00)
Chorea 1 (0.02) 1 (0.05) 0 (0.00)
Coma 1 (0.02) 0 (0.00) 1 (0.05)
Dementia 16 (0.40) 10 (0.50) 6 (0.30)
Dementia Alzheimer's type 7 (0.17) 3 (0.15) 4 (0.20)
Dizziness 4 (0.10) 2 (0.10) 2 (0.10)
Dysarthria 1 (0.02) 1 (0.05) 0 (0.00)
Epilepsy 8 (0.20) 2 (0.10) 6 (0.30)
Guillain-Barre syndrome 1 (0.02) 0 (0.00) 1 (0.05)
Haemorrhage intracranial 3 (0.07) 0 (0.00) 3 (0.15)
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Haemorrhagic stroke 1 (0.02) 0 (0.00) 1 (0.05)
Headache 1 (0.02) 1 (0.05) 0 (0.00)
Hemiparesis 2 (0.05) 1 (0.05) 1 (0.05)
Hepatic encephalopathy 1 (0.02) 0 (0.00) 1 (0.05)
Hypoaesthesia 1 (0.02) 0 (0.00) 1 (0.05)
Mental impairment 1 (0.02) 1 (0.05) 0 (0.00)
Migraine 1 (0.02) 0 (0.00) 1 (0.05)
Movement disorder 1 (0.02) 1 (0.05) 0 (0.00)
Normal pressure hydrocephalus 1 (0.02) 1 (0.05) 0 (0.00)
Parkinsonism 1 (0.02) 1 (0.05) 0 (0.00)
Peripheral sensory neuropathy 1 (0.02) 0 (0.00) 1 (0.05)
Polyneuropathy 1 (0.02) 0 (0.00) 1 (0.05)
Presyncope 2 (0.05) 1 (0.05) 1 (0.05)
Sciatica 2 (0.05) 1 (0.05) 1 (0.05)
Seizure 7 (0.17) 3 (0.15) 4 (0.20)
Spinal claudication 1 (0.02) 1 (0.05) 0 (0.00)
Spinal cord compression 1 (0.02) 0 (0.00) 1 (0.05)
Subarachnoid haemorrhage 2 (0.05) 0 (0.00) 2 (0.10)
Syncope 41 (1.02) 18 (0.89) 23 (1.15)
Temporal lobe epilepsy 3 (0.07) 1 (0.05) 2 (0.10)
Unresponsive to stimuli 1 (0.02) 1 (0.05) 0 (0.00)
Vertebrobasilar insufficiency 1 (0.02) 1 (0.05) 0 (0.00)
Vocal cord paralysis 1 (0.02) 0 (0.00) 1 (0.05)
Cervical radiculopathy 1 (0.02) 0 (0.00) 1 (0.05)
Alcoholic seizure 1 (0.02) 1 (0.05) 0 (0.00)
Cognitive disorder 3 (0.07) 1 (0.05) 2 (0.10)
Vascular dementia 2 (0.05) 1 (0.05) 1 (0.05)
Ischaemic stroke 6 (0.15) 5 (0.25) 1 (0.05)
Partial seizures 1 (0.02) 1 (0.05) 0 (0.00)
Parkinson's disease 4 (0.10) 1 (0.05) 3 (0.15)
Orthostatic intolerance 1 (0.02) 1 (0.05) 0 (0.00)
Carotid arteriosclerosis 1 (0.02) 0 (0.00) 1 (0.05)
Dementia with Lewy bodies 1 (0.02) 1 (0.05) 0 (0.00)
Hypoxic-ischaemic 1 (0.02) 1 (0.05) 0 (0.00)
encephalopathy
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Intensive care unit acquired 1 (0.02) 1 (0.05) 0 (0.00)
weakness
Basilar artery aneurysm 1 (0.02) 0 (0.00) 1 (0.05)
Intracranial mass 2 (0.05) 1 (0.05) 1 (0.05)
Psychiatric disorders 31 (0.77) 12 (0.60) 19 (0.95)
Completed suicide 3 (0.07) 0 (0.00) 3 (0.15)
Confusional state 10 (0.25) 4 (0.20) 6 (0.30)
Delirium 11 (0.27) 6 (0.30) 5 (0.25)
Depression 1 (0.02) 0 (0.00) 1 (0.05)
Suicide attempt 1 (0.02) 0 (0.00) 1 (0.05)
Mental status changes 4 (0.10) 1 (0.05) 3 (0.15)
Major depression 1 (0.02) 1 (0.05) 0 (0.00)
Renal and urinary disorders 94 (2.34) 49 (2.43) 45 (2.25)
Calculus urinary 1 (0.02) 1 (0.05) 0 (0.00)
Glomerulonephritis 1 (0.02) 0 (0.00) 1 (0.05)
Hydronephrosis 4 (0.10) 1 (0.05) 3 (0.15)
Nephrolithiasis 4 (0.10) 2 (0.10) 2 (0.10)
Nephrotic syndrome 1 (0.02) 0 (0.00) 1 (0.05)
Pelvi-ureteric obstruction 1 (0.02) 1 (0.05) 0 (0.00)
Renal colic 1 (0.02) 1 (0.05) 0 (0.00)
Renal disorder 1 (0.02) 1 (0.05) 0 (0.00)
Renal failure 16 (0.40) 11 (0.55) 5 (0.25)
Urinary incontinence 1 (0.02) 0 (0.00) 1 (0.05)
Urinary retention 4 (0.10) 1 (0.05) 3 (0.15)
Renal mass 2 (0.05) 0 (0.00) 2 (0.10)
Renal impairment 2 (0.05) 1 (0.05) 1 (0.05)
Chronic kidney disease 6 (0.15) 2 (0.10) 4 (0.20)
Urethral stenosis 1 (0.02) 0 (0.00) 1 (0.05)
Acute kidney injury 50 (1.25) 28 (1.39) 22 (1.10)
Malnutrition-inflammation- 1 (0.02) 1 (0.05) 0 (0.00)
atherosclerosis syndrome
Immune-mediated renal 1 (0.02) 1 (0.05) 0 (0.00)
disorder
Reproductive system and breast 9 (0.22) 8 (0.40) 1 (0.05)
disorders
Benign prostatic hyperplasia 6 (0.15) 5 (0.25) 1 (0.05)
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Breast hyperplasia 1 (0.02) 1 (0.05) 0 (0.00)
Prostatitis 1 (0.02) 1 (0.05) 0 (0.00)
Erectile dysfunction 1 (0.02) 1 (0.05) 0 (0.00)
Respiratory, thoracic and mediastinal 170 (4.24) 84 (4.17) 86 (4.31)
disorders
Acute pulmonary oedema 3 (0.07) 3 (0.15) 0 (0.00)
Acute respiratory distress 3 (0.07) 3 (0.15) 0 (0.00)
syndrome
Acute respiratory failure 14 (0.35) 5 (0.25) 9 (0.45)
Asthma 1 (0.02) 1 (0.05) 0 (0.00)
Atelectasis 1 (0.02) 0 (0.00) 1 (0.05)
Bronchospasm 2 (0.05) 0 (0.00) 2 (0.10)
Chronic obstructive pulmonary 33 (0.82) 17 (0.84) 16 (0.80)
disease
Dyspnoea 21 (0.52) 11 (0.55) 10 (0.50)
Dyspnoea exertional 1 (0.02) 0 (0.00) 1 (0.05)
Hypercapnia 1 (0.02) 1 (0.05) 0 (0.00)
Hypoxia 2 (0.05) 0 (0.00) 2 (0.10)
Idiopathic pulmonary fibrosis 2 (0.05) 1 (0.05) 1 (0.05)
Interstitial lung disease 3 (0.07) 2 (0.10) 1 (0.05)
Lung disorder 2 (0.05) 1 (0.05) 1 (0.05)
Orthopnoea 1 (0.02) 1 (0.05) 0 (0.00)
Pleural effusion 13 (0.32) 6 (0.30) 7 (0.35)
Pneumonitis 2 (0.05) 1 (0.05) 1 (0.05)
Pneumothorax 5 (0.12) 3 (0.15) 2 (0.10)
Pneumothorax spontaneous 1 (0.02) 0 (0.00) 1 (0.05)
Pulmonary embolism 34 (0.85) 15 (0.74) 19 (0.95)
Pulmonary fibrosis 4 (0.10) 4 (0.20) 0 (0.00)
Pulmonary hypertension 1 (0.02) 0 (0.00) 1 (0.05)
Pulmonary oedema 9 (0.22) 7 (0.35) 2 (0.10)
Pulmonary sarcoidosis 1 (0.02) 1 (0.05) 0 (0.00)
Respiratory arrest 1 (0.02) 0 (0.00) 1 (0.05)
Respiratory failure 29 (0.72) 12 (0.60) 17 (0.85)
Pulmonary mass 1 (0.02) 0 (0.00) 1 (0.05)
Pulmonary arterial 1 (0.02) 1 (0.05) 0 (0.00)
hypertension
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Organising pneumonia 2 (0.05) 2 (0.10) 0 (0.00)
Skin and subcutaneous tissue disorders 4 (0.10) 4 (0.20) 0 (0.00)
Decubitus ulcer 1 (0.02) 1 (0.05) 0 (0.00)
Skin ulcer 3 (0.07) 3 (0.15) 0 (0.00)
Diabetic foot 2 (0.05) 2 (0.10) 0 (0.00)
Social circumstances 2 (0.05) 1 (0.05) 1 (0.05)
Walking disability 1 (0.02) 1 (0.05) 0 (0.00)
Loss of personal independence 1 (0.02) 0 (0.00) 1 (0.05)
in daily activities
Surgical and medical procedures 67 (1.67) 27 (1.34) 40 (2.00)
Aortic valve replacement 1 (0.02) 0 (0.00) 1 (0.05)
Bladder catheterisation 1 (0.02) 1 (0.05) 0 (0.00)
Cardiac pacemaker insertion 2 (0.05) 1 (0.05) 1 (0.05)
Cardioversion 6 (0.15) 3 (0.15) 3 (0.15)
Carotid endarterectomy 1 (0.02) 0 (0.00) 1 (0.05)
Cholecystectomy 1 (0.02) 0 (0.00) 1 (0.05)
Euthanasia 2 (0.05) 1 (0.05) 1 (0.05)
Foot amputation 1 (0.02) 1 (0.05) 0 (0.00)
Hip arthroplasty 9 (0.22) 5 (0.25) 4 (0.20)
Hysterectomy 1 (0.02) 1 (0.05) 0 (0.00)
Leg amputation 1 (0.02) 0 (0.00) 1 (0.05)
Lung lobectomy 2 (0.05) 0 (0.00) 2 (0.10)
Mastectomy 1 (0.02) 0 (0.00) 1 (0.05)
Mitral valve replacement 1 (0.02) 0 (0.00) 1 (0.05)
Resuscitation 1 (0.02) 0 (0.00) 1 (0.05)
Toe amputation 1 (0.02) 0 (0.00) 1 (0.05)
Stent placement 2 (0.05) 0 (0.00) 2 (0.10)
Cardiac pacemaker replacement 4 (0.10) 1 (0.05) 3 (0.15)
Knee operation 1 (0.02) 0 (0.00) 1 (0.05)
Medical device implantation 1 (0.02) 1 (0.05) 0 (0.00)
Coronary revascularisation 1 (0.02) 0 (0.00) 1 (0.05)
Transurethral bladder resection 3 (0.07) 0 (0.00) 3 (0.15)
Medical device removal 1 (0.02) 0 (0.00) 1 (0.05)
Hospitalisation 1 (0.02) 0 (0.00) 1 (0.05)
Prosthesis implantation 1 (0.02) 1 (0.05) 0 (0.00)
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Intervertebral disc operation 1 (0.02) 0 (0.00) 1 (0.05)
Implantable defibrillator 1 (0.02) 0 (0.00) 1 (0.05)
replacement
Medical device change 1 (0.02) 1 (0.05) 0 (0.00)
Haemorrhoid operation 1 (0.02) 1 (0.05) 0 (0.00)
Cardiac resynchronisation 3 (0.07) 2 (0.10) 1 (0.05)
therapy
Cardiac ablation 2 (0.05) 1 (0.05) 1 (0.05)
Aortic valve repair 1 (0.02) 0 (0.00) 1 (0.05)
Eye operation 1 (0.02) 1 (0.05) 0 (0.00)
Hydrocele operation 1 (0.02) 1 (0.05) 0 (0.00)
Skin graft 1 (0.02) 0 (0.00) 1 (0.05)
Bladder polypectomy 1 (0.02) 1 (0.05) 0 (0.00)
Cataract operation 1 (0.02) 0 (0.00) 1 (0.05)
Percutaneous coronary 1 (0.02) 0 (0.00) 1 (0.05)
intervention
Peripheral artery bypass 1 (0.02) 1 (0.05) 0 (0.00)
Large intestinal polypectomy 1 (0.02) 0 (0.00) 1 (0.05)
Transcatheter aortic valve 3 (0.07) 1 (0.05) 2 (0.10)
implantation
Left atrial appendage closure 1 (0.02) 1 (0.05) 0 (0.00)
implant
Vascular disorders 91 (2.27) 44 (2.18) 47 (2.35)
Aortic aneurysm 4 (0.10) 3 (0.15) 1 (0.05)
Aortic aneurysm rupture 3 (0.07) 2 (0.10) 1 (0.05)
Aortic dissection 2 (0.05) 1 (0.05) 1 (0.05)
Aortic stenosis 9 (0.22) 5 (0.25) 4 (0.20)
Arteriosclerosis 3 (0.07) 1 (0.05) 2 (0.10)
Axillary vein thrombosis 1 (0.02) 0 (0.00) 1 (0.05)
Circulatory collapse 2 (0.05) 2 (0.10) 0 (0.00)
Femoral artery aneurysm 1 (0.02) 1 (0.05) 0 (0.00)
Hypertension 3 (0.07) 1 (0.05) 2 (0.10)
Hypertensive crisis 4 (0.10) 2 (0.10) 2 (0.10)
Hypotension 12 (0.30) 6 (0.30) 6 (0.30)
Intermittent claudication 2 (0.05) 1 (0.05) 1 (0.05)
Jugular vein thrombosis 1 (0.02) 1 (0.05) 0 (0.00)
 Overall Apixaban Aspirin
System organ class Preferred term n (%) n (%) n (%)
Orthostatic hypotension 6 (0.15) 1 (0.05) 5 (0.25)
Pelvic venous thrombosis 1 (0.02) 1 (0.05) 0 (0.00)
Peripheral ischaemia 2 (0.05) 1 (0.05) 1 (0.05)
Peripheral vascular disorder 1 (0.02) 1 (0.05) 0 (0.00)
Thrombosis 2 (0.05) 1 (0.05) 1 (0.05)
Venous thrombosis 2 (0.05) 0 (0.00) 2 (0.10)
Shock haemorrhagic 1 (0.02) 0 (0.00) 1 (0.05)
Deep vein thrombosis 13 (0.32) 5 (0.25) 8 (0.40)
Iliac artery stenosis 1 (0.02) 0 (0.00) 1 (0.05)
Haemorrhage 2 (0.05) 2 (0.10) 0 (0.00)
Peripheral artery aneurysm 4 (0.10) 1 (0.05) 3 (0.15)
Neurogenic shock 1 (0.02) 1 (0.05) 0 (0.00)
Hypertensive urgency 2 (0.05) 2 (0.10) 0 (0.00)
Venous thrombosis limb 1 (0.02) 0 (0.00) 1 (0.05)
Peripheral arterial occlusive 8 (0.20) 5 (0.25) 3 (0.15)
disease
Arterial occlusive disease 1 (0.02) 0 (0.00) 1 (0.05)
Peripheral artery stenosis 1 (0.02) 0 (0.00) 1 (0.05)
Peripheral artery thrombosis 1 (0.02) 0 (0.00) 1 (0.05)
Iliac artery restenosis 1 (0.02) 0 (0.00) 1 (0.05)
Product issues 12 (0.30) 8 (0.40) 4 (0.20)
Device malfunction 2 (0.05) 1 (0.05) 1 (0.05)
Device electrical finding 1 (0.02) 1 (0.05) 0 (0.00)
Device lead damage 4 (0.10) 2 (0.10) 2 (0.10)
Lead dislodgement 4 (0.10) 3 (0.15) 1 (0.05)
Device inappropriate shock 1 (0.02) 1 (0.05) 0 (0.00)
delivery
Missing code 7 (0.17) 4 (0.20) 3 (0.15)
Missing code 7 (0.17) 4 (0.20) 3 (0.15)