Stroke Risk Mitigation in Patients with Atrial Fibrillation

Educational Objectives

The goal of this program is to improve strategies for stroke risk mitigation in patients with atrial fibrillation (AF). After hearing and assimilating this program, the clinician will be better able to:

1. Analyze the benefits and risks of various anticoagulant therapies for stroke risk mitigation in patients with AF.
2. Recognize the role of LAA occlusion devices in preventing stroke in patients with AF.
3. Appraise the indications, contraindications, and potential complications following LAA closure.

Summary

Atrial fibrillation (AF): is a culmination of triggering beats and a vulnerable atrial substrate; can occur intermittently (paroxysmal AF) or persist continuously (persistent AF); symptoms vary widely; a common origin of AF is the pulmonary veins; tends to progress over time; AF is associated with various comorbidities, including those that contribute to stroke and heart attack; lifestyle modifications play a role in managing risk factors; a definitive diagnosis of AF requires electrocardiography (ECG) or a continuous (30-sec) ECG (telemetry) strip showing the irregular heart rhythm; risk factors for stroke in patients with AF have been identified and are used to assess individual risk, eg, CHA₂DS₂-VASc score (congestive heart failure, hypertension, age ≥75 yr [doubled], diabetes, stroke [doubled], vascular disease, age 65-74 yr, female sex)

Stroke risk mitigation: anticoagulation therapy is recommended for individuals with a CHA₂DS₂-VASc score of ≥2 for men and ≥3 for women; Friberg et al (2012) — demonstrated a significant reduction in stroke rates with anticoagulation, particularly warfarin; as the CHA₂DS₂-VASc score increased, the potential benefit of anticoagulation became more pronounced; the rate of intracranial hemorrhage (ICH) was 1%

Medications: large-scale clinical trials involving >18,000 patients have compared warfarin with newer anticoagulants, eg, direct thrombin inhibitors and anti-Xa agents; these studies suggest that the newer drugs may offer similar or even superior efficacy in reducing ischemic or unknown strokes, particularly in patients with higher risk profiles; the rate of ICH is lower with direct oral anticoagulants (DOACs; gastrointestinal bleeding can occur); each additive therapy further reduces the risk for stroke; evidence suggests superior outcomes with DOACs vs warfarin; cardiology guidelines in the United States strongly recommend DOACs for eligible patients, classifying it as a class 1 recommendation

Pathogenesis: a comprehensive analysis of 23 studies (1996) revealed that, in the absence of rheumatic heart disease, the left atrial appendage (LAA) is the primary source of clots in 91% of AF-related strokes; multiple studies (2009, 2017) have shown that patients undergoing AF ablation had their procedures canceled because of blood clots in the LAA; in the ASSERT trial, Healey et al (2012) monitored 2500 patients with heart rhythm devices and found that the risk for stroke significantly increased after 24 hr of continuous AF; this finding challenges the traditional belief that any amount of AF increases stroke risk and raises the possibility that the underlying condition of the atrium, or atrial substrate, might play a more significant role in stroke risk than previously thought; evidence suggests that there is a transient increase in stroke risk immediately following an AF episode, which then returns to baseline in 2 to 4 wk; underlying atrial cardiomyopathy may contribute to the increased risk, especially in cases of prolonged AF episodes

Mechanism of occlusion devices: the primary mechanism of action for LAA occlusion devices is not only the physical occlusion of the LAA, but also the process of endothelialization; by 6 wk, the endothelium grows over the device and seals off that part of the heart from the rest of the circulation; this process takes ≈45 days to complete

Procedure: cardiac computed tomography (CT) with contrast allows for detailed 3-dimensional reconstruction of the heart, including the LAA; this enables precise measurement of the appendage’s dimensions, crucial for selecting an appropriate sized device for occlusion; the procedure is minimally invasive, typically performed through a single femoral venous access; a specialized catheter is used to navigate to the LAA, where contrast is injected to visualize its anatomy; once the appropriate device is chosen, it is deployed and secured in place; post-procedure monitoring with transesophageal echocardiography (TEE) confirms successful occlusion

Evidence: the WATCHMAN device was approved by the US Food and Drug Administration (FDA) based on a clinical trial comparing it with warfarin; PROTECT AF trial (Reddy et al [2015]) — involved a complex treatment regimen; initially, all patients were placed on both warfarin and aspirin; after 45 days, after TEE confirmed the seal, warfarin was discontinued, and patients transitioned to a combination of aspirin and clopidogrel (Plavix); at the 6-mo mark, patients were further reduced to aspirin monotherapy or even no antiplatelet therapy; this approach, while initially more intensive, aims to balance the risks for stroke and bleeding associated with anticoagulation; meta-analysis by Sohaib et al (2015) — suggested that LAA occlusion significantly reduces risk for hemorrhagic stroke; this was attributed to the discontinuation of anticoagulant therapy, a known cause of bleeding

Medication regimen: a recent FDA approval has allowed for a simplified treatment regimen for patients undergoing LAA occlusion; instead of initiating anticoagulation therapy on day 0, patients may directly start dual antiplatelet therapy (DAPT) with aspirin and clopidogrel; this is particularly beneficial for patients who have concerns about anticoagulation because of personal preferences or underlying medical conditions; recent analysis by Carvalho et al (2023) — showed that, for patients undergoing LAA occlusion, initiating DOAC therapy without any initial antiplatelet therapy does not increase risk for device thrombosis or stroke during the first 45 days after procedure; this approach may offer some benefit by reducing the risk for bleeding complications associated with antiplatelet therapy; Della Rocca et al (2021) — initiated patients on half-dose DOACs (apixaban 2.5 mg twice daily, rivaroxaban 10 mg once daily) with aspirin for the first 45 days; after 45 days, aspirin was discontinued and patients continued on half-dose DOACs; results of the study showed that half-dose DOAC regimen was associated with a lower risk for adverse events compared with standard antithrombotic therapy

Checklists: patients who cannot tolerate any form of anticoagulation, even half-dose DOACs for 6 wk, are not ideal candidates; additionally, patients with severe kidney dysfunction, requiring dialysis, or those with significant bleeding risks may not be suitable; ability to receive intravenous heparin during the procedure is required, as well as TEE for monitoring, and femoral vein access for device delivery; patients considering LAA occlusion should be evaluated for surgical suitability, including anesthesia tolerance; accurate sizing of the occlusion device is crucial; this often involves imaging studies, eg, chest CT, TEE; previous imaging studies may be sufficient if they provide adequate information about the LAA size and morphology; the goal is to select a device that is neither too small nor too large to ensure optimal occlusion and minimize the risk for complications

Evidence: PRAGUE-17 study (Osmancik et al [2020]) — compared the efficacy and safety of apixaban vs LAA occlusion using the WATCHMAN device; both strategies were found to be noninferior in preventing stroke, systemic embolism, and major bleeding; the study employed shorter-term (3 mo) DAPT regimen, suggesting that a more streamlined approach may be feasible

Anticoagulation failure: evidence suggests that patients with AF who experience a stroke while on anticoagulant therapy tend to have less severe strokes compared with those who are not on anticoagulation

Lee et al (2021): found that patients with LAA occlusion devices experienced less severe strokes compared with those without the device, as measured by the modified Rankin Score; patients who had experienced a stroke despite being on anticoagulant therapy were compared with controls who underwent LAA occlusion because of bleeding complications and were unable to continue anticoagulation; the study group, who had not responded to anticoagulation, showed a slight reduction in the expected rate of stroke after the procedure; the study suggests that LAA occlusion may provide additional protection against stroke in patients who have experienced a stroke despite being on anticoagulant therapy; while the overall reduction in stroke risk was modest, it highlights a potential benefit for this high-risk patient group

LAAOS III study (Whitlock et al [2021]): investigated the impact of surgical LAA occlusion during cardiac surgery on stroke risk; patients who underwent the procedure and continued anticoagulation were at significantly lower risk for stroke and systemic embolism compared with those who did not have the procedure; combining surgical LAA occlusion with anticoagulation may offer additional protection against stroke in high-risk patients; future studies — eg, LAAOS IV, will explore the potential benefits of percutaneous LAA occlusion in combination with anticoagulation

Readings

Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg. 1996;61(2):755-759. doi:10.1016/0003-4975(95)00887-X; Carvalho PEP, Gewehr DM, Miyawaki IA, et al. Network meta-analysis of initial antithrombotic regimens after left atrial appendage occlusion. J Am Coll Cardiol. 2023;82(18):1765-1773. doi:10.1016/j.jacc.2023.08.010; Della Rocca DG, Magnocavallo M, Di Biase L, et al. Half-dose direct oral anticoagulation versus standard antithrombotic therapy after left atrial appendage occlusion. JACC Cardiovasc Interv. 2021;14(21):2353-2364. doi:10.1016/j.jcin.2021.07.031; Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J. 2012;33(12):1500-1510. doi:10.1093/eurheartj/ehr488; Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fibrillation and the risk of stroke [published correction appears in N Engl J Med. 2016 Mar 10;374(10):998. doi: 10.1056/NEJMx160004]. N Engl J Med. 2012;366(2):120-129. doi:10.1056/NEJMoa1105575; Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893-2962. doi:10.1093/eurheartj/ehw210; Lee OH, Kim YD, Kim JS, et al. Percutaneous left atrial appendage occlusion yields favorable neurological outcomes in patients with non-valvular atrial fibrillation. Korean Circ J. 2021;51(7):626-638. doi:10.4070/kcj.2020.0527; Osmancik P, Herman D, Neuzil P, et al. Left atrial appendage closure versus direct oral anticoagulants in high-risk patients with atrial fibrillation. J Am Coll Cardiol. 2020;75(25):3122-3135. doi:10.1016/j.jacc.2020.04.067; Sohaib SM, Fox KF. A meta-analysis of left atrial appendage closure for stroke prevention in atrial fibrillation-adding to the debate but elements remain unresolved. J Thorac Dis. 2015;7(8):E226-E229. doi:10.3978/j.issn.2072-1439.2015.08.03; Whitlock RP, Belley-Cote EP, Paparella D, et al. Left atrial appendage occlusion during cardiac surgery to prevent stroke. N Engl J Med. 2021;384(22):2081-2091. doi:10.1056/NEJMoa2101897; Writing Committee Members, Joglar JA, Chung MK, et al. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines [published correction appears in J Am Coll Cardiol. 2024 Mar 5;83(9):959. doi: 10.1016/j.jacc.2024.01.020] [published correction appears in J Am Coll Cardiol. 2024 Jun 25;83(25):2714. doi: 10.1016/j.jacc.2024.05.033]. J Am Coll Cardiol. 2024;83(1):109-279. doi:10.1016/j.jacc.2023.08.017.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Frisch was recorded at the 22nd Annual Cerebrovascular Update, held March 16-17, 2023, in Philadelphia, PA, and presented by Thomas Jefferson University. For information about upcoming CME activities from this presenter, please visit jefferson.edu. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

NE160101

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.