Management Options for Atrial Fibrillation Patients Experiencing Stroke Despite Anticoagulation

Atrial fibrillation (AF) is a leading cause of ischemic stroke, and oral anticoagulation (OAC) remains the cornerstone of stroke prevention. However, so-called “breakthrough” thromboembolic events occur in a significant subset of patients (residual risk ~1-2%/year), raising questions about alternative management strategies for secondary prevention. Prior studies found that switching between DOAC subtypes or adding antiplatelet agents does not seem helpful in reducing the high recurrence rate of up to 10% in the first year after “breakthrough” strokes. A recent propensity-matched registry study conducted by Maarse et al. sheds light on the role of left atrial appendage occlusion (LAAO) as a potential intervention in these high-risk cases.

Maarse and colleagues conducted a large international cohort study to evaluate outcomes in patients who underwent LAAO compared to those who continued OAC following a stroke or other thromboembolic event while already on anticoagulation. The study spanned 21 centers over 12 years (2010–2022) and used propensity score matching to reduce selection bias. The primary endpoint was the time to first ischemic stroke within a two-year follow-up period, with secondary endpoints including rates of systemic embolism, transient ischemic attack (TIA), major bleeding, and all-cause mortality.

The study population included 433 patients in the LAAO group (mean age: 72 years, 39% women) and 433 matched controls in the OAC group (mean age: 73 years, 36% women). Both groups had a mean CHA2DS2-VASc score of 5.0, emphasizing their high baseline stroke risk. A history of intracerebral hemorrhage (ICH) was more prevalent in the LAAO group (10%) compared to the OAC group (2%). The annualized stroke rate was significantly lower in the LAAO group at 2.8% compared to 8.9% in the OAC group, with a hazard ratio of 0.33 (95% CI: 0.19–0.58; p < 0.001). Major procedural complications occurred in 7% of patients undergoing LAAO, with pericardial effusion and vascular access complications being the most common issues. Post-procedural management varied, with 67% of patients discontinuing OAC and others continuing adjunctive antiplatelet or anticoagulant therapy. Device-related thrombus was observed in 6% of patients, necessitating individualized approaches to post-procedural antithrombotic regimens. This study highlights LAAO as a feasible and potentially effective option for AF patients who experience stroke despite OAC. Mechanically excluding the left atrial appendage, a common source of thrombus formation in AF, LAAO provides a method to circumvent the limitations of pharmacologic therapies. The observed reduction in recurrent stroke rates supports its utility in this high-risk population. However, procedural risks, while relatively low, require careful consideration, particularly in elderly or frail patients. Decisions regarding post-procedural therapy should be tailored to individual patient characteristics, including bleeding history and device-related findings. The findings of this study pave the way for further exploration through randomized controlled trials. The ongoing ELAPSE and LAAOS-4 trials are expected to provide robust evidence comparing the efficacy of LAAO combined with OAC versus OAC alone in patients with a history of stroke despite anticoagulation. These results will be pivotal in shaping clinical practice.

Conclusion

For AF patients with recurrent thromboembolic events despite adequate anticoagulation, LAAO presents a promising strategy for secondary stroke prevention. Advances in procedural safety and patient selection criteria are likely to enhance its role in managing this high-risk group. Nevertheless, validation through randomized clinical trials remains essential to establish its place in therapeutic protocols and wherever possible, stroke physicians should try to participate in the trials and include this high-risk patients.

References:

Johnson et al. Residual Stroke Risk Among Patients With Atrial Fibrillation Prescribed Oral Anticoagulants: A Patient-Level Meta-Analysis From COMBINE AF JAHA 2024 Sep 3;13(17):e034758. doi: 10.1161/JAHA.123.034758.

Maarse M et al. Left atrial appendage occlusion vs standard of care after ischemic stroke despite anticoagulation. JAMA Neurol. 2024;81(11):1150. doi:10.1001/jamaneurol.2024.2882.

Polymeris et al. Aetiology, secondary prevention strategies and outcomes of ischaemic stroke despite oral anticoagulant therapy in patients with atrial fibrillation JNNP 2022 Jun;93(6):588-598. doi: 10.1136/jnnp-2021-328391.