How do you manage patients with atrial fibrillation having a thromboembolic infarct despite being on adequate anticoagulation?

This scenario is always challenging. In terms of anticoagulation, the efficacy of DOACs in preventing embolic events in AF patients is around 70%, which is impressive compared to warfarin but not foolproof. In cases of a second embolic event while on anticoagulation, two reasonable approaches are often considered: continuing with the same agent or switching to another.

Before deciding on an approach, I ensure the patient has been consistently adherent to their medication. Patients may inadvertently miss doses, take medication at incorrect intervals, or face challenges like cost, which can lead to medication conservation. Clinically driven factors such as dose adjustments or temporary cessation for procedures may also contribute to suboptimal...

In addition to what Dr. @Dr. First Last and Dr. @Dr. First Last said, I would like to add that evaluating for underlying hyper-coagulable states like occult or active malignancy or anti-phospholipid antibody syndrome. There have been reports of higher DOAC failure rates in those with aggressive forms of cancers, especially GI, lung, and ovarian. If there is evidence of APLS, then management would be switching to warfarin and if there is underlying aggressive or occult malignancy then therapeutic lovenox (DOACs were non-inferior to Lovenox; gold standard remains Lovenox for thromboembolism precipitated by malignancy). Additionally, evaluate if any drugs induce the metabolism (including certain chemotherapeutic agents) of the respective DOAC,...

If the DOAC is not apixaban, I would switch to that drug, since it has shown superior efficacy in some studies. If it is apixaban, I would consider switching to warfarin after making sure that the stroke workup has been completed, including hypercoagulable states, cardiac abnormalities, etc.

Previous answer (October 06, 2024)

I would strongly consider L atrial appendage closure. If not an option, switch anticoagulants, perhaps to warfarin.

Updating some of the available evidence regarding ischemic stroke while on DOAC for atrial fibrillation, since much of the discussion was in 2024:

This topic of "breakthrough stroke" has been investigated ever since the 2020 paper by David Seiffge using multi-center pooled observational registry data that made 2 observations: 1) Those with AF who had stroke on oral anticoagulants constitute a higher-risk group (ischemic stroke recurrence ~9% per year) and 2) switching OAC does not appear to change the risk (Seiffge PMID 32052481). Subsequent meta-analysis of observational studies in 2025 (Romoli et al., PMID 40758940) and another large registry study in 2026 (D'Anna et al., PMID 42048077) confirm the same finding that switching to another an...