Current Gaps in the Provision of Safe and Effective Anticoagulation in Atrial Fibrillation and the Potential for Factor XI-Directed Therapeutics

Shaun G Goodman; Denis Roy; Charles V Pollack Jr; Kori Leblanc; Kevin F Kwaku; Geoffrey D Barnes; Marc P Bonaca; Mellanie True Hills; Elena Campello; John Fanikos; Jean M Connors; Jeffrey I Weitz

doi:10.1097/HPC.0000000000000351

Current Gaps in the Provision of Safe and Effective Anticoagulation in Atrial Fibrillation and the Potential for Factor XI-Directed Therapeutics

Crit Pathw Cardiol. 2024 Feb 21. doi: 10.1097/HPC.0000000000000351. Online ahead of print.

Authors

Affiliations

¹ Division of Cardiology, St Michael's Hospital, Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto, ON, and Canadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada.
² Department of Medicine and Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada.
³ Department of Emergency Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
⁴ Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
⁵ Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
⁶ Frankel Cardiovascular Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
⁷ Division of Cardiology, CPC Clinical Research, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA.
⁸ StopAfib.org, American Foundation for Women's Health, Decatur, TX, USA.
⁹ General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Padova, Italy.
¹⁰ Department of Pharmacy, Brigham and Women's Hospital, Boston, MA, USA.
¹¹ Hematology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹² McMaster University, Hamilton, ON, Canada, and Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada.

PMID: 38381695
DOI: 10.1097/HPC.0000000000000351

Abstract

The global prevalence of atrial fibrillation is rapidly increasing, in large part due to the aging of the population. Atrial fibrillation is known to increase the risk of thromboembolic stroke by five times, but it has been evident for decades that well-managed anticoagulation therapy can greatly attenuate this risk. Despite advances in pharmacology (such as the shift from vitamin K antagonists to direct oral anticoagulants) that have increased the safety and convenience of chronic oral anticoagulation in atrial fibrillation, a preponderance of recent observational data indicates that protection from stroke is poorly achieved on a population basis. This outcomes deficit is multifactorial in origin, stemming from a combination of underprescribing of anticoagulants (often as a result of bleeding concerns by prescribers), limitations of the drugs themselves (drug-drug interactions, bioaccumulation in renal insufficiency, short half-lives that result in lapses in therapeutic effect, etc.), and suboptimal patient adherence that results from lack of understanding/education, polypharmacy, fear of bleeding, forgetfulness, and socioeconomic barriers, among other obstacles. Often this adherence is not reported to treating clinicians, further subverting efforts to optimize care. A multidisciplinary, interprofessional panel of clinicians met during the 2023 International Society of Thrombosis and Haemostasis Congress to discuss these gaps in therapy, how they can be more readily recognized, and the potential for Factor XI-directed anticoagulants to improve the safety and efficacy of stroke prevention. A full appreciation of this potential requires a re-evaluation of traditional teaching about the "coagulation cascade" and decoupling the processes that result in (physiologic) hemostasis and (pathologic) thrombosis. The panel discussion is summarized and presented here.