When Direct Oral AnticoagulantsShould Not Be Standard Treatment – JACC State-of-the-Art Review
Antoine Bejjani, MD,a,b,c,* Candrika D. Khairani, MD, MMSC,a,b,* Ali Assi, MD, MBA,d Gregory Piazza, MD, MS,a,b,d Parham Sadeghipour, MD,e,f Azita H. Talasaz, PHARMD,g,h John Fanikos, RPH, MBA,i Jean M. Connors, MD,j Deborah M. Siegal, MD, MSC,k Geoffrey D. Barnes, MD, MSC,l Karlyn A. Martin, MD, MS,m Dominick J. Angiolillo, MD, PHD,n Dawn Kleindorfer, MD,o Manuel Monreal, MD, PHD,p David Jimenez, MD, PHD,q Saskia Middeldorp, MD, PHD,r Mitchell S.V. Elkind, MD, MS,s,t Christian T. Ruff, MD, MPH,b Samuel Z. Goldhaber, MD,a,b Harlan M. Krumholz, MD, SM,u,v,w Roxana Mehran, MD,x Mary Cushman, MD, MSC,y,z John W. Eikelboom, MBBS,aa Gregory Y.H. Lip, MD,bb,cc Jeffrey I. Weitz, MD,dd,ee Renato D. Lopes, MD, PHD,ff,gg Behnood Bikdeli, MD, MSa,b,r,hh
a) Thrombosis Research Group, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA;
b) Cardiovascular Medicine Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA;
c) Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA;
d) Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA;
e) Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran;
f) Clinical Trial Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran;
g) Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran;
h) Virginia Commonwealth University, Richmond, Virginia, USA;
i) Department of Pharmacy, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA;
j) Hematology Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA;
k) Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada;
l) Frankel Cardiovascular Center, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA;
m) Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA;
n) Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, USA;
o) University of Cincinnati, Cincinnati, Ohio, USA;
p) Cátedra de Enfermedad Tromboembólica, Universidad Católica San Antonio de Murcia, Spain;
q) Respiratory Department, Hospital Ramón y Cajal and Medicine Department, Universidad de Alcalá (Instituto de Ramón y Cajal de Investigación Sanitaria), Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain;
r) Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands;
s) Department of Neurology, Vagelos College of Physicians and Surgeons, New York, New York, USA;
t) Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA;
u) Yale New Haven Hospital/Yale Center for Outcomes Research and Evaluation, New Haven, Connecticut, USA;
v) Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut, USA;
w) Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine,
For most patients, direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists for stroke prevention in atrial fibrillation and for venous thromboembolism treatment. However, randomized controlled trials suggest that DOACs may not be as efficacious or as safe as the current standard of care in conditions such as mechanical heart valves, thrombotic antiphospholipid syndrome, and atrial fibrillation associated with rheumatic heart disease. DOACs do not provide a net benefit in conditions such as embolic stroke of undetermined source. Their efficacy is uncertain for conditions such as left ventricular thrombus, catheter-associated deep vein thrombosis, cerebral venous sinus thrombosis, and for patients with atrial fibrillation or venous thrombosis who have end-stage renal disease. This paper provides an evidence-based review of randomized controlled trials on DOACs, detailing when they have demonstrated efficacy and safety, when DOACs should not be the standard of care, where their safety and efficacy are uncertain, and areas requiring further research. (J Am Coll Cardiol 2024;83:444–465) © 2024 by the American College of Cardiology Foundation.