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Published on: February 28, 2012
Direct Oral Anticoagulant Failures in Atrial Fibrillation With Stroke: Retrospective Admission Analysis and Novel
David Z Rose1, Jane Y Chang2, Xiyan Yi3
1Department of Neurology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Insights
Direct oral anticoagulants (DOAC) are often prescribed for atrial fibrillation (AF) patients. In cases of breakthrough acute ischemic stroke (AIS), alternative causes like compliance issues or other conditions are more likely than DOAC failure.
Area of Science:
- Neurology
- Cardiology
- Pharmacology
Background:
- Acute ischemic stroke (AIS) in patients with nonvalvular atrial fibrillation (AF) on direct oral anticoagulants (DOACs) presents a clinical challenge.
- Switching anticoagulants has not proven effective in preventing recurrent AIS.
- Understanding the reasons for 'DOAC failures' is crucial for patient management.
Purpose of the Study:
- To investigate alternative etiologies for AIS in patients with known AF who are prescribed DOACs.
- To introduce and apply a novel classification schema (CLAMP) to categorize DOAC failures.
- To differentiate between DOAC 'Pseudo-failures' and 'Crypto-failures'.
Main Methods:
- A 6-year retrospective study of AIS admissions in patients prescribed DOAC for AF.
- Utilized the CLAMP schema: Compliance, Lacunes, Arteriopathy, Malignancy, Patent Foramen Ovale.
- Performed forward logistic regression analysis on DOAC subgroups.
Main Results:
- Out of 4890 AIS admissions, 87 patients were on DOAC for AF, yielding a 14.4% DOAC failure rate.
- DOAC 'Pseudo-failures' (with identified alternate causes) comprised 77% of cases.
- Compliance issues (48.9%) and Malignancy (26.1%) were the most frequent Pseudo-failures. Crypto-failures were associated with lower CHADSVASc scores and more frequent with rivaroxaban.
Conclusions:
- In AIS patients with AF on DOACs, identified alternative etiologies (Pseudo-failures) are significantly more common than true DOAC failures (Crypto-failures).
- The CLAMP schema provides a structured approach for diagnosing and managing AIS in patients with AF on DOACs.
- This classification aids in identifying specific causes beyond anticoagulation inadequacy.
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.
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