Direct Oral Anticoagulant "Pseudo-Failure" Vs. "True Failure" To Prevent Ischemic Stroke In Nonvalvular Atrial Fibrillation

Background: Despite the efficacy of Direct Oral Anticoagulants (DOACs) in Nonvalvular Atrial Fibrillation (NVAF), some patients may still develop an ischemic stroke while taking this medication. This can be from a primary efficacy problem, called DOAC “True failure” (due to drug absorption, metabolism, or clearance), or DOAC “Pseudo-failure” (due to alternate causes of stroke, not the NVAF). We aim to study the factors contributing to DOAC Pseudo-failures and isolate DOAC True Failure rates. Methods: IRB-approved, retrospective study of NVAF patients on DOAC who developed ischemic stroke between Jan 2012 and Dec 2017. Variables reviewed include DOAC Pseudo-failure causes listed in the mnemonic CHAMP: C for Compliance concerns (adherence [held for procedure, ran out, or discontinued], incorrect dose, or incorrect frequency [QD vs BID]); H for Hypertensive lacunar disease; A for Arterial diseases (such as Atherosclerosis [intra- or extra-cranial, carotid or vertebral arterial stenosis or dissection]); M for Malignant cancer or other hypercoagulable states; and P for Patent Foramen Ovale (PFO). Results: We identified 87 NVAF patients on DOAC who presented with ischemic stroke: 18 on Dabigatran, 37 on Apixaban and 32 on Rivaroxaban. Of those, 67 patients (77%) had at least one of the CHAMP variables (DOAC Pseudo-failure) while 20 (23%) were DOAC True failures. Compliance concerns were responsible for nearly half (49%) of the Pseudo-failures, followed by Malignancy/hypercoagulability (26%), Arterial disease (17%), HTN (5.7%) and PFO (2.3%). True Failure was lowest for Dabigatran (5.6%) followed by Apixaban (16%) and highest with Rivoraxaban (41%) despite its high compliance rate of 66%. Compliance for the BID DOACs (Dabigatran and Apixaban) were similar at 39 % and 43%, respectively. Conclusion: Patients on DOAC for NVAF who develop ischemic stroke are three times more likely to have another identifiable etiology. Compliance concerns, Cancer/Hypercoagulability, and arterial disease represent over 90% of DOAC Pseudo-failures. Thus, providers should educate patients on correct DOAC doses and frequencies, and screen presumed DOAC failures with scans of the chest, abdomen and pelvis in addition to intracranial and extracranial vessel imaging.