Direct Oral Anticoagulant Failures in Atrial Fibrillation With Stroke: Retrospective Admission Analysis and Novel Classification System

David Z Rose; Jane Y Chang; Xiyan Yi; Kevin Kip; Yuanyuan Lu; N Corbin Hilker; Abdelrahman Beltagy

doi:10.1177/19418744231161390

Direct Oral Anticoagulant Failures in Atrial Fibrillation With Stroke: Retrospective Admission Analysis and Novel Classification System

Neurohospitalist. 2023 Jul;13(3):256-265. doi: 10.1177/19418744231161390. Epub 2023 May 12.

Authors

David Z Rose¹, Jane Y Chang², Xiyan Yi³, Kevin Kip⁴, Yuanyuan Lu⁵, N Corbin Hilker¹, Abdelrahman Beltagy⁶

Affiliations

¹ Department of Neurology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
² Ascendant Biotech Inc., Foster City, CA, USA.
³ University of South Dakota, Sioux Falls, SD, USA.
⁴ University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
⁵ College of Public Health, University of South Florida, Tampa, FL, USA.
⁶ Providence Spokane Neuroscience Institute, Spokane, WA, USA.

PMID: 37441203
PMCID: PMC10334065 (available on 2024-07-01)
DOI: 10.1177/19418744231161390

Abstract

Introduction: Breakthrough acute ischemic stroke (AIS) in patients with known, nonvalvular Atrial Fibrillation (AF), on Direct Oral Anticoagulants (DOAC), is an ongoing clinical conundrum. Switching anticoagulants was shown to be ineffective in preventing recurrent AIS. Systematic, patient-level chart review of so-called "DOAC failures" may offer insight into this phenomenon.

Methods: We conducted an IRB-approved, 6-year, retrospective study of AIS admissions, already prescribed DOAC for known AF. We sought plausible, alternative reasons for the AIS using a novel classification schema, CLAMP: C for Compliance concerns, L for Lacunes (small-vessel disease), A for Arteriopathy (atherosclerosis, web, or vasculitis), M for Malignancy, and P for Patent Foramen Ovale (PFO). These categories were labeled as DOAC "Pseudo-failures." Conversely, absence of CLAMP variables were labeled as DOAC "Crypto-failures" conceivably from AF itself ("atriopathy") or pharmacokinetic/pharmacogenomic dysfunction (ie, altered DOAC absorption, clearance, metabolism, or genetic polymorphisms). Forward logistic regression analysis was performed on prespecified DOAC subgroups.

Results: Of 4890 AIS admissions, 606 had AF, and 87 were previously prescribed DOAC (14.4% overall DOAC failure rate, 2.4% annualized over 6 years). Pseudo-failures comprised 77%: Compliance concerns (48.9%), Lacunes (5.7%), Arteriopathy (17.0%), Malignancy (26.1%), and PFO (2.3%). Crypto-failures comprised 23%, had lower CHADSVASc scores (AOR = .65, P = .013), and occurred more with rivaroxaban (41%) than apixaban (16%) or dabigatran (5.6%).

Conclusion: In AIS patients with known AF, DOAC Pseudo-failures, with identified alternate etiologies, are 3 times more likely than DOAC Crypto-failures. The CLAMP schema represents a novel approach to diagnostic classification and therapeutic adjustments in patients already prescribed DOAC for AF.

Keywords: electrophysiology/atrial fibrillation < clinical specialty; ischemic attack; stroke < cerebrovascular disorders; transient < cerebrovascular disorders.