2018 anticoagulation therapy

Anticoagulation
Therapy
Joe F. Lau
Geoffrey D. Barnes
Michael B. Streiff
Editors

123


Anticoagulation Therapy


Joe F. Lau • Geoffrey D. Barnes
Michael B. Streiff
Editors

Anticoagulation
Therapy


Editors
Joe F. Lau, MD, PhD
Associate Professor of Cardiology
Department of Cardiology
Zucker School of Medicine
at Hofstra/Northwell
Northwell Health
Manhasset, NY, USA

Geoffrey D. Barnes, MD, MSc

Assistant Professor
Division of Internal Medicine
Frankel Cardiovascular Center at the
University of Michigan
Ann Arbor, MI, USA

Michael B. Streiff, MD
Professor of Medicine and Pathology
Division of Hematology
Department of Medicine
The Johns Hopkins University
School of Medicine
Baltimore, MD, USA

ISBN 978-3-319-73708-9
ISBN 978-3-319-73709-6
/>
(eBook)

Library of Congress Control Number: 2018935389
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Preface

Since the introduction of vitamin K antagonists in the 1950s, the field of anticoagulation has evolved considerably to include an ever-increasing number
of new therapeutic agents and procedures for thromboembolic disease. The
rapidity of change presents a challenge for busy healthcare providers to stay
abreast of the latest developments in the management of thrombotic disease.
This book outlines the current state of antithrombotic therapy which will
serve as a foundation upon which the field will inevitably continue to grow
and develop. We hope that the readers will find this book to be a valuable
resource and reliable reference for patient care.
Manhasset, NY, USA
Ann Arbor, MI, USA
Baltimore, MD, USA

Joe F. Lau, MD, PhD
Geoffrey D. Barnes, MD, MSc
Michael B. Streiff, MD

v

Acknowledgments

For my parents, who sacrificed and gave their all so their children can succeed; for my wife, Nora, and my sons, Justin and Daniel, who have continued
to inspire me through their unwavering and loving support; and to my mentors and colleagues over the years—I thank you for keeping doors open for
the kid who dreamed big.—Joe F. Lau
For my parents, who nurtured my love of science and medicine; for my husband, Grant, and my daughter, Gillian, who give me endless support and
encouragement; and to my mentors, colleagues, and patients who have taught
me the true joy of medicine.—Geoffrey D. Barnes
I would like to acknowledge my wife, Lauren, and my children, Zachary and
Madeline, who have been a source of pride and joy and who have been unbelievably supportive despite my crazy schedule and extremely patient and tolerant of my working vacations and weekends. I would also like to thank my
parents, Richard and Jenny Streiff, as well as the mentors who taught and
inspired me including Richard R. Streiff, MD; Craig S. Kitchens, MD;
Richard Lottenberg, MD; William R. Bell, MD, PhD; Jerry L. Spivak, MD;
and Thomas S. Kickler, MD.—Michael B. Streiff

vii


Contents

1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Joe F. Lau, Geoffrey D. Barnes, and Michael B. Streiff

1

Part I Anticoagulants
2

Warfarin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Gregory C. Hadlock, Allison E. Burnett, and Edith A. Nutescu

3

Unfractionated Heparin and Low-Molecular-Weight
Heparin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Rhynn J. Malloy, Jessica Rimsans, Megan Rhoten,
Katelyn Sylvester, and John Fanikos

4

Parenteral Anticoagulants: Direct Thrombin Inhibitors
and Pentasaccharides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Meghan L. Fletcher and Allison E. Burnett

9

31

59

5

Direct Oral Anticoagulants . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Natalie S. Evans

6

Anticoagulation Reversal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Deborah Hornacek and Marcelo P. V. Gomes

7

Transitioning Between Anticoagulants . . . . . . . . . . . . . . . . . . . . 133
Maya Serhal and Marcelo P. V. Gomes

Part II

87

Clinical Applications of Anticoagulant Therapy

8

The Anticoagulation Clinic. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
Nathan P. Clark and Daniel M. Witt

9

Perioperative Management of Anticoagulants . . . . . . . . . . . . . . 175
Ibrahim M. Ali, Alexander Volodarskiy, and Joe F. Lau

10

Acute Coronary Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
Nilay K. Patel and Sammy Elmariah

11

Antithrombotic Therapy for Patients
with Atrial Fibrillation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217
Kyla M. Lara and Jonathan L. Halperin

ix


Contents

x

12

Anticoagulant Strategies for Electrophysiology Procedures . . . 239
Stuart J. Beldner and David L. Stern

13

Anticoagulation for Cardiac Prosthetic Devices:
Prosthetic Heart Valves, Left Ventricular Assist Devices,
and Septal Closure Devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253
Matthew T. Crim, Supriya Shore, Suegene K. Lee,
and Bryan J. Wells

14

Anticoagulation in Venous Thromboembolism . . . . . . . . . . . . . 297
Geoffrey D. Barnes and Elizabeth T. Renner

15

Thrombophilic States . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
Adriana Guigova and Tony Philip

16

Thrombophilia Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345
Teresa L. Carman

17

Heparin-Induced Thrombocytopenia . . . . . . . . . . . . . . . . . . . . . 359
Emily Downs, Svetlana Goldman, Surabhi Palkimas,
and Aditya M. Sharma

18

Anticoagulation Therapy in Pregnant Patients . . . . . . . . . . . . . 391
Steven A. Savella, Jessica A. Kvasic, and Joe F. Lau

19

Anticoagulation in the Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . 409
Ruchika Harisingani, Ibrahim M. Ali, Bhakti Shah,
and Salonie Pereira

20

Anticoagulation in the Patient with Cancer . . . . . . . . . . . . . . . . 425

Simon Mantha, Dipti Gupta, Chadi Salmane, Mansour
Khaddr, Gerald A. Soff, and Richard Steingart

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 441


Contributors

Ibrahim M. Ali Department of Cardiology, Northwell Health, Zucker
School of Medicine at Hofstra/Northwell, Manhasset, NY, USA
Geoffrey D. Barnes Department of Internal Medicine, Division of
Cardiovascular Medicine, Frankel Cardiovascular Center at the University of
Michigan, Ann Arbor, MI, USA
Stuart J. Beldner Department of Cardiology, Northwell Health, Zucker
School of Medicine at Hofstra/Northwell, Manhasset, NY, USA
Allison E. Burnett University of New Mexico College of Pharmacy,
Albuquerque, NM, USA
Teresa L. Carman Division of Cardiovascular Medicine, University
Hospitals Cleveland Medical Center, Cleveland, OH, USA
Department of Medicine, Case Western Reserve University School of
Medicine, Cleveland, OH, USA
Nathan P. Clark Clinical Pharmacy Anticoagulation and Anemia Service,
Kaiser Permanente Colorado, Aurora, CO, USA
Matthew T. Crim Department of Medicine, Division of Cardiology, Emory
University School of Medicine, Atlanta, GA, USA
Emily Downs Department of Surgery, Division of Thoracic and
Cardiovascular Surgery, University of Virginia Medical Center, University of
Virginia, Charlottesville, VA, USA
Sammy Elmariah Division of Cardiology, Department of Medicine,
Massachusetts General Hospital, Boston, MA, USA

Natalie S. Evans Department of Cardiovascular Medicine, Section of
Vascular Medicine, Cleveland Clinic, Cleveland, OH, USA
John Fanikos Department of Pharmacy, Brigham and Women’s Hospital,
Boston, MA, USA
Meghan L. Fletcher Inpatient Pharmacy Department, University of New
Mexico Hospital, Albuquerque, NM, USA
Svetlana Goldman Department of Pharmacy, University of Virginia Medical
Center, University of Virginia, Charlottesville, VA, USA
xi


xii

Marcelo P. V. Gomes Department of Cardiovascular Medicine, Section of
Vascular Medicine, Cleveland Clinic, Cleveland, OH, USA
Adriana Guigova Division of Hematology/Oncology, Department of
Medicine, Zucker School of Medicine at Hofstra/Northwell, Northwell
Health, Lake Success, NY, USA
Dipti Gupta Department of Medicine, Memorial Sloan Kettering Cancer
Center, New York, NY, USA
Gregory C. Hadlock Inpatient Pharmacy Department, University of New
Mexico Hospital, Albuquerque, NM, USA
Jonathan L. Halperin The Cardiovascular Institute, Mount Sinai Medical
Center, New York, NY, USA
Ruchika Harisingani Department of Medicine, Northwell Health, Zucker
School of Medicine at Hofstra/Northwell, Manhasset, NY, USA
Deborah Hornacek Department of Cardiovascular Medicine, Section of
Vascular Medicine, Cleveland Clinic, Cleveland, OH, USA
Mansour Khaddr Department of Medicine, Memorial Sloan Kettering
Cancer Center, New York, NY, USA

Jessica A. Kvasic Department of Medicine, Zucker School of Medicine at
Hofstra/Northwell, Northwell Health, Manhasset, NY, USA
Kyla M. Lara Department of Medicine, The Icahn School of Medicine at
Mount Sinai, New York, NY, USA
Joe F. Lau Department of Cardiology, Zucker School of Medicine at Hofstra/
Northwell, Northwell Health, Manhasset, NY, USA
Suegene K. Lee Department of Medicine, Division of Cardiology, Emory
University School of Medicine, Atlanta, GA, USA
Rhynn J. Malloy Department of Pharmacy, Brigham and Women’s Hospital,
Boston, MA, USA
Simon Mantha Department of Medicine, Memorial Sloan Kettering Cancer
Center, New York, NY, USA
Edith A. Nutescu Department of Pharmacy Systems, Outcomes and Policy,
Center for Pharmacoepidemiology and Pharmacoeconomic Research, The
University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA
Surabhi Palkimas Department of Pharmacy, University of Virginia Medical
Center, University of Virginia, Charlottesville, VA, USA
Nilay K. Patel Division of Cardiology, Department of Medicine,
Massachusetts General Hospital, Boston, MA, USA
Salonie Pereira Department of Medicine, Northwell Health, Zucker School
of Medicine at Hofstra/Northwell, Manhasset, NY, USA

Contributors


Contributors

xiii

Tony Philip Division of Hematology/Oncology, Department of Medicine,

Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Lake
Success, NY, USA
Elizabeth T. Renner Anticoagulation Service, Faculty Group Practice:
Pharmacy Innovations and Partnerships, University of Michigan, Ann Arbor,
MI, USA
Megan Rhoten Department of Pharmacy, Brigham and Women’s Hospital,
Boston, MA, USA
Jessica Rimsans Department of Pharmacy, Brigham and Women’s Hospital,
Boston, MA, USA
Chadi Salmane Department of Medicine, Memorial Sloan Kettering Cancer
Center, New York, NY, USA
Steven A. Savella Department of Cardiology, Zucker School of Medicine at
Hofstra/Northwell, Northwell Health, Manhasset, NY, USA
Maya Serhal Department of Cardiovascular Medicine, Section of Vascular
Medicine, Cleveland Clinic, Cleveland, OH, USA
Bhakti Shah Department of Medicine, Northwell Health, Zucker School of
Medicine at Hofstra/Northwell, Manhasset, NY, USA
Aditya M. Sharma Department of Medicine, Cardiovascular Medicine
Division, Heart and Vascular Center, University of Virginia Medical Center,
University of Virginia, Charlottesville, VA, USA
Supriya Shore Department of Medicine, Division of Cardiology, Emory
University School of Medicine, Atlanta, GA, USA
Gerald A. Soff Department of Medicine, Memorial Sloan Kettering Cancer
Center, New York, NY, USA
Richard Steingart Department of Medicine, Memorial Sloan Kettering
Cancer Center, New York, NY, USA
David L. Stern Department of Cardiology, Northwell Health, Zucker School
of Medicine at Hofstra/Northwell, Manhasset, NY, USA
Michael B. Streiff Division of Hematology, Department of Medicine,
The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Katelyn Sylvester Department of Pharmacy, Brigham and Women’s
Hospital, Boston, MA, USA
Alexander Volodarskiy Department of Cardiology, New York-Presbyterian/
Queens, Flushing, NY, USA
Bryan J. Wells Department of Medicine, Division of Cardiology, Emory
University School of Medicine, Atlanta, GA, USA
Daniel M. Witt University of Utah College of Pharmacy, Salt Lake City,
UT, USA


About the Editors

Joe F. Lau, MD, PhD, FACC, FASE, FSVM,
RPVI is Associate Professor of Cardiology at the
Zucker School of Medicine at Hofsta/Northwell.
Dr. Lau is an attending cardiologist and vascular
medicine specialist at Northwell Health, the largest integrated health system in New York State,
where he serves as the Director of Vascular
Medicine and Medical Director of the NonInvasive Vascular Laboratory. Dr. Lau has an
extensive clinical practice with research goals
that focus on both cardiac and vascular diseases, while publishing and lecturing frequently within the field. His clinical practice emphasizes on caring for
patients with thrombotic disorders such as atrial fibrillation and venous
thromboembolism. Dr. Lau is also currently involved with numerous clinical
trials, observational studies, and investigator-initiated trials. His research
interests include evaluating the mechanisms of vascular and thrombotic complications associated with cancer and cancer therapies. Dr. Lau is actively
involved with national vascular medicine and cardiovascular societies, with
leadership roles in both the American Heart Association and the American
College of Cardiology, for which he is currently a member of the ACC
Scientific Sessions Program Committee and Peripheral Vascular Disease
Section Leadership Council.

Geoffrey D. Barnes, MD, MSc, FACC, RPVI is
a cardiologist and vascular medicine specialist at
the University of Michigan. He has a long-standing interest in anticoagulation care and the care
of patients with thrombotic disorders, including
atrial fibrillation and venous thromboembolism.
In addition to his clinical practice in vascular
medicine, his research aims to improve systems
of care for patients on anticoagulants and with thrombotic disorders, such as
atrial fibrillation and venous thromboembolism. He is the co-director of the
Michigan Anticoagulation Quality Improvement Initiative and has received
funding from the NIH to improve anticoagulation care delivery. He is an
active leader of many national and international thrombosis and cardiovascular societies and organizations, including the American College of Cardiology,
xv


xvi

the American Heart Association, the International Society on Thrombosis and
Haemostasis, the Society for Vascular Medicine, the National PERT
Consortium, and the Anticoagulation Forum.
Michael B. Streiff, MD, FACP is a hematologist who specializes in the management of venous
thromboembolism and anticoagulation. He is codirector of the Johns Hopkins Venous
Thromboembolism Collaborative that has developed innovative information technology strategies that have led to dramatic improvements in
VTE prevention and management at Johns
Hopkins Medical Institutions. Their work has
won awards from the North American Thrombosis
Forum and the Centers for Disease Control and Prevention. He chairs the
Venous Thromboembolism Guideline Committee for the National
Comprehensive Cancer Network and has served on several international consensus panels to develop evidence-based guidelines for the management of
VTE. He is a board member of the Anticoagulation Forum and the president

of the Medical and Scientific Advisory Board for the National Blood Clot
Alliance. Dr. Streiff and the Johns Hopkins Anticoagulation Management
Service team have played a key role in developing evidence-based guidelines
and electronic order sets for anticoagulation therapy at Johns Hopkins
Medical Institutions. He has published over 150 articles and book chapters
focusing on topics in VTE management and thrombosis and hemostasis and
delivered over 300 lectures at local, national, and international meetings.

About the Editors


Abbreviations

ABC
ABW
ACA
ACC
ACCP
ACF
ACS
ACT
ADP
AERS
AF
AHA
AMS
APC
APC-r
APS
aPTT

ASA
ASD
ASH
AST
AT
ATE
AV
AVM
AVR
BAL
β2GP-1
BID
BMI
CABG
CAD
CBC
CDC
CDTM
CFX
CI

Age, biomarkers, and clinical history score
Adjusted body weight
Anticardiolipin antibody
American College of Cardiology
American College of Chest Physicians
Anticoagulation Forum
Acute coronary syndrome
Activated clotting time
Adenosine diphosphate

Adverse Event Report System
Atrial fibrillation
American Heart Association
Anticoagulation Management Service
Activated Protein C
Activated protein C resistance
Antiphospholipid antibody syndrome
Partial thromboplastin time
Aspirin
Atrial septal defect
American Society of Hematology
Aspartate aminotransferase
Antithrombin
Arterial thromboembolism
Atrioventricular
Arteriovenous malformation
Aortic valve replacement
Bronchoalveolar lavage
β2-Glycoprotein-1 antibody
Bis in die (twice a day)
Body mass index
Coronary artery bypass graft
Coronary artery disease
Complete blood count
Center for Disease Control and Prevention (USA)
Collaborative drug therapy management
Chromogenic factor X
Confidence interval
xvii

Abbreviations

xviii

CKD
CKD-EPI
CMR
CrCl
COR
COX-1,2
CPB
CRRT
DAPT
DCCV
DCT
DDAVP
DES
DIC
dL
DOAC
dRVVT
DTI
dTT
DVT
DW
EACTS
ECG
ECMO
ECT

EGD
eGFR
ELISA
ERCP
ESC
ESRD
ET
ETP
FDA
FIRM
FFP
FSVM
FVa
FVL
GFR
GI
GPI
HAS-BLED

Chronic kidney disease
Chronic Kidney Disease Epidemiology Collaboration
formula
Cardiac magnetic resonance imaging
Creatinine clearance
Class of recommendation
Cyclooxygenase-1, 2
Cardiopulmonary bypass
Continuous renal replacement therapy
Dual antiplatelet therapy
Direct current cardioversion

Direct clotting time
Desmopressin acetate
Drug-eluting stent
Disseminated intravascular coagulation
Deciliter
Direct oral anticoagulant
Dilute Russell’s viper venom time
Direct thrombin inhibitor
Dilute thrombin time
Deep vein thrombosis
Dosing weight
European Association for Cardio-Thoracic Surgery
Electrocardiogram
Extracorporeal membrane oxygenation
Ecarin clotting time
Esophagogastroduodenoscopy
Estimated glomerular filtration rate
Enzyme-linked immunosorbent assay
Endoscopic retrograde cholangiopancreatography
European Society of Cardiology
End-stage renal disease
Essential thrombocythemia (also known as essential
thrombocytosis)
Endogenous thrombin potential
Food and Drug Administration (USA)
Focal impulse and rotor modulation
Fresh frozen plasma
Fellow of the Society of Vascular Medicine
Activated factor V
Factor V Leiden mutation

Glomerular filtration rate
Gastrointestinal
Glycoprotein IIb/IIIa inhibitor
Hypertension, abnormal renal/liver function, stroke,
bleeding history or predisposition, labile INRs, elderly
(> 65 years old), use of drugs that promote bleeding
excess, or alcohol


Abbreviations

xix

Hct
HD
HEMORR2HAGES

HEP
HERDOO2

HFS
Hgb
HIT
HITTS
HMW
HR
HR
HRS
HTN
IBW

ICD
ICH
IM
INR
IPC
IQR
ISHLT
ISTH
IU
IV
IVC
LA
LAA
LAFB
LBBB
LBW
LD
LDL
LMWH
LOE
LV
LVAD
LVEF
MACE
MDRD
mg
MI

Hematocrit
High dose

Hepatic or renal disease, ethanol abuse, malignancy,
older age (age > 75 years), reduced platelet count or
function, hypertension (uncontrolled), anemia, genetic
factors, excessive fall risk, and stroke.
HIT Expert Probability
Hyperpigmentation, edema, or redness in either leg;
D-dimer level ≥ 250 μg/L; obesity with body mass
index ≥ 30; or older age, ≥ 65 years
Heart Failure Society
Hemoglobin
Heparin-induced thrombocytopenia
Heparin-induced thrombocytopenia thrombosis
syndrome
High-molecular-weight
Hazard ratio
Heart rate
Heart Rhythm Society
Hypertension
Ideal body weight
Implantable cardioverter defibrillator
Intracranial hemorrhage, intracerebral hemorrhage
Intramuscular
International normalized ratio
Intermittent pneumatic compression
Interquartile range
International Society for Heart & Lung Transplantation
International Society on Thrombosis and Haemostasis
International units
Intravenous
Inferior vena cava

Lupus anticoagulant
Left atrial appendage
Left anterior fascicular block
Left bundle branch block
Lean body weight
Low dose
Low-density lipoprotein
Low-molecular-weight heparin
Level of evidence
Left ventricular
Left ventricular assist device
Left ventricular ejection fraction
Major adverse cardiovascular events
Modification of Diet in Renal Disease formula
Milligrams
Myocardial infarction


Abbreviations

xx

MRA
MRI
MRV
MTHFR
MVR
NCBAP
NBTE
NOAC

NPO
NSAID
NSTE-ACS
NSTEMI
NT-proBNP
NVAF
OAC
OBRI
OCP
OD
OR
PAD
PaGIA
PAI-1
PAR-1
PC
PCC
PCI
PD
PE
PEO-CO
PF4
PFO
PGM
P-gp
PICC
PK
PNH
PNP
PO

POC
PS
PSM
PST
PT
PTAV
PV
PVI

Magnetic resonance angiography
Magnetic resonance imaging
Magnetic resonance venography
Methylenetetrahydrofolate reductase
Mitral valve replacement
National Certification Board for Anticoagulation
Providers
Nonbacterial thrombotic endocarditis
Novel oral anticoagulant, non-vitamin K antagonist
oral anticoagulant
Nil per os—nothing by mouth
Nonsteroidal anti-inflammatory drug
Non-ST-segment acute coronary syndromes
Non-ST-segment elevation myocardial infarction
N-terminal pro-B-type natriuretic peptide
Non-valvular atrial fibrillation
Oral anticoagulation
Outpatient bleeding risk index
Oral contraceptive pills
Optical density
Odds ratio

Peripheral artery disease
Particle gel immunoassay
Plasminogen activator inhibitor 1
Protease-activated receptor-1
Protein C
Prothrombin complex concentrate
Percutaneous coronary intervention
Pharmacodynamics
Pulmonary embolism
Polyethoxylated castor oil
Platelet factor 4
Patent foramen ovale
Prothrombin gene mutation
P-glycoprotein
Peripherally inserted central catheters
Pharmacokinetics
Paroxysmal nocturnal hemoglobinuria
Platelet neutralization procedure
Per os (per oral)
Point-of-care
Protein S
Patient self-management
Patient self-testing
Prothrombin time
Percutaneous transluminal aortic valvuloplasty
Polycythemia vera
Pulmonary vein isolation


Abbreviations

xxi

RBBB
RCT
RR
RRR
SC
SCD
SD
SLE
SQ
SRA
START/STOPP
STEMI
STS
SVT
SVT
TAFI
TAVR
TBW
TEE
THA
TIA
TKA
TNK
TOAT
TRALI
TSOAC
TT

TTE
TTR
UA
UFH
USPTF
VATS
Vd
VEGF
VKA
VKOR
VSD
VT
VTE
vWF
WHO

Right bundle branch block
Randomized control/controlled trial
Relative risk
Relative risk ratio
Subcutaneous
Sequential compression devices
Standard deviation
Systemic lupus erythematosus
Subcutaneous
Serotonin release assay
Screening tool to alert doctors to right treatment/
screening tool of older persons’ prescriptions
ST-segment elevation myocardial infarction
Society of Thoracic Surgeons

Superficial vein thrombosis
Supraventricular tachycardia
Thrombin-activatable fibrinolysis inhibitor
Transcatheter aortic valve replacement
Total body weight
Transesophageal echocardiogram
Total hip arthroplasty
Transient ischemia attack
Total knee arthroplasty
Tenecteplase
Triple oral anticoagulant therapy
Transfusion-related acute lung injury
Target-specific oral anticoagulants
Thrombin time
Transthoracic echocardiogram
Time-in-therapeutic range
Unstable angina
Unfractionated heparin
US Preventative Task Force
Video-assisted thoracoscopic surgery
Volume of distribution
Vascular endothelial growth factor
Vitamin K antagonist
Vitamin K epoxide reductase
Ventricular septal defect
Ventricular tachycardia
Venous thromboembolism
von Willebrand factor
World Health Organization

Trial Abbreviations

ACUITY
ACUTE

ADVANCE
AFFIRM
AMPLIFY

AMPLIFY-EXT
ANNEXA-A
ANNEXA-R
APEX

APOLLO

APPRAISE
ARISTOTLE
AREVA
ARTEMIS
ASAP

Acute Catheterization and Urgent Intervention
Triage Strategy trial
Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) Multicenter
Study
Action in Diabetes and Vascular Disease: Preterax
and Diamicron MR Controlled Evaluation trial
Atrial Fibrillation Follow-up Investigation of

Rhythm Management
Apixaban for the Initial Management of Pulmonary
Embolism and Deep-Vein Thrombosis as FirstLine Therapy trial
Apixaban for Extended Treatment of Venous
Thromboembolism trial
Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors Apixaban
Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors Rivaroxaban
Acute Medically III VTE (Venous Thromboembolism) Prevention with Extended Duration
Betrixaban trial
Fondaparinux combined with intermittent pneumatic compression vs. intermittent pneumatic
compression alone for prevention of venous
thromboembolism after abdominal surgery: a
randomized, double-blind comparison
Apixaban for Prevention of Acute Ischemic and
Safety Events
Apixaban for Reduction in Stroke and Other
Thromboembolic Events in Atrial Fibrillation trial
Anticoagulation et Remplacement Valvulaire
(France)
Affordability and Real-world Antiplatelet Treatment
Effectiveness After Myocardial Infarction Study
ASA Plavix Feasibility Study with Watchman
Left Atrial Appendage Closure Technology study

xxiii


Trial Abbreviations

xxiv

ASAP-TOO
ASPIRE
ATBAT

ATLAS-TIMI-46
ATLAS-TIMI-51
ATLAS ACS 2-TIMI 51

ATOLL

ATRIA
ATTRACT

AUGUSTUS
AUREC
AVERROES
AXAFA

BRAVO-3
BRIDGE

BRUISE CONTROL
CALISTO
CASSINI

Assessment of the Watchman Device in Patients
Unsuitable for Oral Anticoagulation
Low-Dose Aspirin for Preventing Recurrent
Venous Thromboembolism

Anticoagulant Therapy with Bivalirudin to Assist
in the performance of percutaneous coronary
intervention in patients with heparin-induced
Thrombocytopenia
Rivaroxaban versus placebo in patients with acute
coronary syndromes
Rivaroxaban in patients with a recent acute coronary syndrome
Anti-Xa Therapy to Lower cardiovascular events
in addition to Aspirin with or without thienopyridine therapy in Subjects with Acute Coronary
Syndrome 2—Thrombolysis in Myocardial
Infarction 51 Trial
Acute STEMI Treated with Primary PCI and IV
Enoxaparin or UFH to Lower Ischemic and
Bleeding Events at Short- and Long-Term
Follow-up trial
Anticoagulation and Risk Factors in Atrial Fibrillation study
Acute Venous Thrombosis: Thrombus Removal
with Adjunctive Catheter-Directed Thrombolysis
trial
Apixaban in Patients With Atrial Fibrillation and
ACS/PCI
Austrian Study of Recurrent Venous Thromboembolism
Apixaban Versus Acetylsalicylic Acid to Prevent
Stroke in Atrial Fibrillation trial
Apixaban During Atrial Fibrillation Catheter
Ablation: Comparison to Vitamin K Antagonist
Therapy
Bivalirudin Versus Heparin Anticoagulation in
Transcatheter Aortic Valve Replacement
Bridging Anticoagulation in Patients who Require

Temporary Interruption of Warfarin Therapy for
an Elective Invasive Procedure or Surgery
Bridge or Continue Coumadin for Device Surgery
Randomized Controlled Trial
Comparison of Arixtra in Lower Limb Superficial
Vein Thrombosis with Placebo trial
Efficacy and Safety of Rivaroxaban Prophylaxis
Compared with Placebo in Ambulatory Cancer
Patients Initiating Systemic Cancer Therapy and
at High Risk for Venous Thromboembolism


Trial Abbreviations

xxv

CATCH
CAVENT
CLOT

COMPASS
CRUSADE

DAWA

EINSTEIN
EINSTEIN CHOICE
EINSTEIN PE

EINSTEIN DVT

EMANATE

ENGAGE AF-TIMI 48

ENSURE-AF

ENTRUST-PCI

EQUINOX

ESSENCE
EUROMAX

Comparison of Acute Treatments in Cancer
Haemostasis trial
Catheter-Directed Venous Thrombolysis in Acute
Iliofemoral Vein Thrombosis study
Randomized Comparison of Low-MolecularWeight Heparin versus Oral Anticoagulant
Therapy for the Prevention of Recurrent Venous
Thromboembolism in Patients with Cancer
Cardiovascular Outcomes for People Using
Anticoagulation Strategies trial
Can Rapid Risk Stratification of Unstable Angina
Patients Suppress Adverse Outcomes With Early
Implementation of the ACC/AHA Guidelines
study
Dabigatran Versus Warfarin After Bioprosthesis
Valve Replacement for the Management of Atrial
Fibrillation Postoperatively study

Oral Rivaroxaban for Symptomatic Venous
Thromboembolism
Rivaroxaban or Aspirin for Extended Treatment
of Venous Thromboembolism
Oral Direct Factor Xa Inhibitor Rivaroxaban in
Patients With Acute Symptomatic Pulmonary
Embolism
Oral Direct Factor Xa Inhibitor Rivaroxaban in
Patients With Acute Symptomatic Deep-Vein
Thrombosis
Apixaban compared with parenteral heparin and/
or vitamin K antagonist in patients with nonvalvular atrial fibrillation undergoing cardioversion
Effective Anticoagulation with Factor Xa Next
Generation in Atrial Fibrillation – Thrombolysis
in Myocardial Infarction 48
Edoxaban Versus Enoxaparin–Warfarin in
Patients Undergoing Cardioversion of Atrial
Fibrillation Trial
Edoxaban Treatment Versus Vitamin K
Antagonist in Patients With Atrial Fibrillation
Undergoing Percutaneous Coronary Intervention
Bioequipotency Study of Idrabiotaparinux and
Idraparinux in Patients With Deep Venous
Thrombosis of the Lower Limbs
Efficacy and Safety of Subcutaneous Enoxaparin
in Unstable Angina and Non-Q-Wave MI trial
European Ambulance Acute Coronary Syndrome
Angiography Trial

Trial Abbreviations

xxvi

FUTURA/OASIS 8

GARFIELD
GELIA
GLORIA-AF
GUSTO
HEAT-PPCI
HOKUSAI-VTE
HOPE-2
HORIZONS-AMI
ISAR-TRIPLE
LIWACAP

LOWERING-IT
MATISSE DVT

MATISSE PE

MOMENTUM
OASIS
OASIS-5

OASIS-6

Fondaparinux Trial with Unfractionated Heparin
During Revascularization in Acute Coronary

Syndromes
Global Anticoagulant Registry in the FIELD
registry
German Experience with Low Intensity Anticoagulation
Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation
Global Use of Strategies to Open Occluded
Coronary Arteries
Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention
Edoxaban for the long-term treatment of venous
thromboembolism
(Heart Outcomes Prevention Evaluation) placebocontrolled randomized clinical trial
Harmonizing Outcomes with Revascularization
and Stents in Acute Myocardial Infarction trial
Triple Therapy in Patients on Oral Anticoagulation
After Drug-Eluting Stent Implantation
Low-intensity oral anticoagulant plus low-dose
aspirin during the first six months versus standardintensity oral anticoagulant therapy after mechanical heart valve replacement: a pilot study of
low-intensity warfarin and aspirin in cardiac
prostheses
LOWERing the INtensity of oral anticoaGulant
Therapy trial
Mondial Assessment of Thromboembolism treatment Initiated by Synthetic pentasaccharide with
Symptomatic Endpoints—Deep Vein Thrombosis
Mondial Assessment of Thromboembolism treatment Initiated by Synthetic pentasaccharide with
Symptomatic Endpoints—Pulmonary Embolism
A Fully Magnetically Levitated Circulatory
Pump for Advanced Heart Failure
Organization to Assess Strategies in Acute
Ischemic Syndromes
Comparison of Fondaparinux and Enoxaparin in

Acute Coronary Syndromes: The Fifth Organization
to Assess Strategies in Acute Ischemic Syndromes
Investigators
The Effects of Fondaparinux on Mortality and
Reinfarction in Patients with Acute ST-segment
Elevation Myocardial Infarction: The Sixth
Organization to Assess Strategies in Acute Ischemic
Syndromes Investigators


Trial Abbreviations

xxvii

OCEAN
ORBIT
PEITHO
PEGASUS
PENTHIFRA-Plus
PERIOP 2

PIONEER AF-PCI

POPular TAVI
PREFER in AF
PREPIC
PREVENT-HIT

PREVAIL

PROACT
PROTECT AF

RE-ALIGN

RE-CIRCUIT

RECORD
RE-COVER

Optimal Anticoagulation for Higher Risk Patients
Post-Catheter Ablation for Atrial Fibrillation Trial
Outcomes Registry for Better Informed Treatment
of Atrial Fibrillation registry
Pulmonary Embolism Thrombolysis trial
Placebo on a Background of Aspirin-Thrombolysis
in Myocardial Infarction
Pentasaccharide in Hip-Fracture Surgery Plus
A Safety and Effectiveness of LMWH vs Placebo
Bridging Therapy for Patients on Long Term
Warfarin Requiring Temporary Interruption of
Warfarin
A Study Exploring Two Strategies of Rivaroxaban
and One of Oral Vitamin K Antagonist in Patients
With Atrial Fibrillation Who Undergo
Percutaneous Coronary Intervention trial
Antiplatelet Therapy for Patients Undergoing
Transcatheter Aortic Valve Implantation
Prevention of Thromboembolic Events—European
Registry in Atrial Fibrillation

Prevention du Risque d'Embolie Pulmonaire par
Interruption Cave study
A Comparative Clinical and Pharmacoeconomic
Study Comparing Argatroban® IV vs Desirudin
SC for Patients With Suspected Heparin-Induced
Thrombocytopenia (HIT)With or Without
Thrombosis Syndrome (HIT/TS)
Watchman LAA Closure Device in Patients With
Atrial Fibrillation Versus Long-Term Warfarin
Therapy
Prospective Randomized On-X Anticoagulation
Clinical Trial
Watchman Left Atrial Appendage System for
Embolic Protection in Patients With Atrial Fibrillation
Randomized, phase II study to Evaluate the
sAfety and pharmacokinetics of oraL dabIGatran
etexilate in patients after heart valve replacemeNt
trial
Randomized Evaluation of Dabigatran Etexilate
Compared to warfarIn in pulmonaRy Vein
Ablation: Assessment of an Uninterrupted periproCedUral antIcoagulation sTrategy
REgulation of Coagulation in major Orthopedic
surgery reducing the Risk of DVT and PE trial
A Phase III, Randomized, Double Blind, Parallelgroup Study of the Efficacy and Safety of Oral
Dabigatran Etexilate 150 mg Twice Daily Compared


Trial Abbreviations

xxviii

RE-DEEM

RE-DUAL

RE-LY
REMATCH
RE-MEDY

RE-NOVATE

RE-SONATE

REVERSE-AD
RIETE
ROCKET-AF

SAVE-ONCO

to Warfarin (INR 2.0–3.0) for 6 Month Treatment of
Acute Symptomatic Venous Thromboembolism
(VTE), Following Initial Treatment (5–10 Days)
With a Parenteral Anticoagulant Approved for This
Indication
RandomizEd Dabigatran Etexilate Dose Finding
Study in Patients With Acute Coronary Syndromes
Post Index Event With Additional Risk Factors for
Cardiovascular Complications Also Receiving
Aspirin and Clopidogrel: Multi-centre, Prospective,
Placebo Controlled, Cohort Dose Escalation Study

Randomized Evaluation of Dual Therapy with
Dabigatran vs. Triple Therapy Strategy with
Warfarin in Patients with NVAF that have undergone PCI with Stenting
Randomized
Evaluation
of
Long-Term
Anticoagulation Therapy trial
Long-Term Use of a Left Ventricular Assist
Device for End-Stage Heart Failure
A Phase III, Randomised, Multicenter, Doubleblind, Parallel-group, Active Controlled Study to
Evaluate the Efficacy and Safety of Oral
Dabigatran Etexilate (150 mg Bid) Compared to
Warfarin (INR 2.0–3.0) for the Secondary
Prevention of Venous Thromboembolism
A Phase III Randomised, Parallel Group, Doubleblind, Active Controlled Study to Investigate the
Efficacy and Safety of Orally Administered
220 mg Dabigatran Etexilate Capsules (110 mg
Administered on the Day of Surgery Followed by
220 mg Once Daily) Compared to Subcutaneous
40 mg Enoxaparin Once Daily for 28–35 Days, in
Prevention of Venous Thromboembolism in
Patients With Primary Elective Total Hip Arthroplasty Surgery
Twice-daily Oral Direct Thrombin Inhibitor
Dabigatran Etexilate in the Long-Term Prevention
of Recurrent Symptomatic VTE
A Study of the RE-VERSal Effects of Idarucizumab on Active Dabigatran
Registro Informatizado de Pacientes con Enfermedad TromboEmbólica (Spain)
Rivaroxaban Once Daily Oral Direct Factor Xa
Inhibition Compared with Vitamin K Antagonism

for Prevention of Stroke and Embolism Trial in
Atrial Fibrillation trial
Semuloparin for prevention of VTE in Cancer
Patients Receiving Chemotherapy trial


Trial Abbreviations

xxix

SPORTIF
SYNERGY

ULTIMA
VENTURE AF

WARFASA
WOA

WOEST

XANTUS
X-VeRT

Stroke Prevention using ORal Thrombin Inhibitor
in atrial Fibrillation
Superior Yield of the New strategy of Enoxaparin,
Revascularization and GlYcoprotein IIb/IIIa inhibitors trial
ULTrasound Accelerated Thrombolysis of
PulMonAry Embolism trial

A randomized, open-label, active-controlled multicenter study to evaluate the safety of rivaroxaban and vitamin K antagonists in subjects
undergoing catheter ablation for atrial fibrillation
Aspirin for Preventing the Recurrence of Venous
Thromboembolism
Comparing warfarin to aspirin after aortic valve
replacement with the St. Jude Medical Epic heart
valve bioprosthesis
What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation
and coronary StenTing trial
Xarelto for Prevention of Stroke in Patients with
Atrial Fibrillation
EXplore the efficacy and safety of once-daily oral
riVaroxaban for the prEvention of caRdiovascular events in patients with nonvalvular aTrial
fibrillation scheduled for cardioversion trial