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Safer Paths Better Outcomes: Advancing Secondary Stroke Prevention Through Factor XIa Innovation | Module 1: Applying Evidence-Based Antithrombotic Strategies

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Description

This program is supported by an independent education grant from Bayer. This education program is only available to healthcare professionals in the USA.

In this on-demand session, leading stroke prevention expert Dr. Jeffrey L. Saver translates high-impact evidence from the AHA/ASA guidelines and landmark trials into actionable clinical decisions. Through concise case-based simulations, he explores the integration of novel Factor XIa inhibition, an emerging therapeutic target that potentially uncouples pathologic thrombosis from hemostasis.

Prefer to read instead? Read our Key Clinical Summary here.

Accreditation: AffinityCE designates this activity for 0.25 AMA PRA Category 1 Credit™

Session Highlights

The Therapeutic "Gap": FXIa inhibitors aim to address the critical clinical challenge of preventing recurrent ischemic stroke without increasing life-threatening bleeding. Unlike current therapies, FXIa inhibition potentially uncouples pathologic thrombosis from normal hemostasis.
Mechanism of Action: Activated Factor XI (FXIa) plays a major role in the thrombin amplification loop that leads to thrombus formation, but only a minor role in the initial hemostatic plug formation required to stop bleeding.
Genetic Evidence for Safety: Clinical data show that individuals with genetically lower levels of FXI have a reduced risk of ischemic stroke and venous thromboembolism (VTE). Crucially, these individuals do not exhibit a corresponding increase in spontaneous bleeding events.
PACIFIC-Stroke Findings: This Phase 2b trial demonstrated that Asundexian, a direct oral FXIa inhibitor, achieved >90% inhibition of FXIa activity. Results showed a dose-dependent reduction in recurrent ischemic stroke or TIA without a significant increase in major bleeding compared to placebo.
Emerging Phase III Trials: Large-scale international studies, including OCEANIC-STROKE and LIBREXIA-STROKE, are currently underway to definitively determine if adding Asundexian to standard antiplatelet therapy is superior for long-term secondary prevention in non-cardioembolic stroke patients.

Who Should Watch

Pharmacists
Neurologists
Multidisciplinary stroke care teams
Primary care physicians
Critical care physicians
Hospitalists
Advanced practice providers
Nurses
Care managers involved in multidisciplinary post-stroke care

Presented by

Jeffrey L. Saver, MD, FAHA, FAAN, FANA, is a Distinguished Professor and Director of the UCLA Comprehensive Stroke and Vascular Neurology Program. A world-renowned expert in stroke treatment and prevention, he has authored over 870 research articles and served as the principal investigator for landmark trials including FAST-MAG and SWIFT PRIME. Dr. Saver is a former Chair of the AHA Stroke Council, and a recipient of the World Stroke Organization Lifetime Research Award.

Continuing Education Information

Commercial support: This activity received monetary support through an independent education grant from Bayer.

This continuing education activity will be provided by AffinityCE and MedAll. This activity will provide continuing education credit for pharmacists.

Disclosures

Jeffrey L. Saver, MD, FAHA, FAAN, FANA has disclosed financial interests or relationships within the past 36 months with the following ineligible companies: Consultant for Abbott, Aeromics, Bayer, Biogen, Boehringer Ingelheim, BrainQ, BrainsGate, CSL Behring, Medtronic USA, Roche, Stream Medical, Johnson & Johnson, MIVI Neuroscience and Occlutech. Stock Options from MindRhythm, Neuronics Medical, Rapid Medical.

These disclosures are provided in accordance with ACCME standards to ensure transparency and uphold the integrity of continuing education. Dr. Saver does not intend to reference any unlabeled or unapproved uses of products during the presentation.

AffinityCE staff, MedAll staff, as well as planners and reviewers, have no relevant financial relationships with ineligible companies to disclose.

Mitigation of Relevant Financial Relationships

AffinityCE adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of a CME activity, including faculty, planners, reviewers, or others, are required to disclose all relevant financial relationships with ineligible companies. Relevant financial relationships were mitigated by the peer review of content by non-conflicted reviewers prior to the commencement of the program.

Activity Accreditation for Health Professions

Physicians

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and MedAll. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.

AffinityCE designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Physician Assistants

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and MedAll. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.

AffinityCE designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credits™. Physician assistants should claim only the credit commensurate with the extent of their participation in the activity.

Nurse Practitioners

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of AffinityCE and MedAll. AffinityCE is accredited by the ACCME to provide continuing medical education for physicians.

AffinityCE designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credits™. Nurse practitioners should claim only the credit commensurate with the extent of their participation in the activity.

Nurses & Other Professionals

All other health care professionals completing this continuing education activity will be issued a statement of participation indicating the number of hours of continuing education credit. This may be used for professional education CE credit. Please consult your accrediting organization or licensing board for their acceptance of this CE activity.

System Requirements

Mobile device (e.g., large-format smart phone; laptop or tablet computer) or desktop computer with a video display of at least 1024 × 768 pixels at 24-bit color depth, capable of connecting to the Internet at broadband or faster speeds, with a current version Internet browser and popular document viewing software (e.g., Microsoft Office, PDF viewer, image viewer) installed. Support for streaming or downloadable audio-visual materials (e.g., streaming MP4, MP3 audio) in hardware and software may be required to view, review, or participate in portions of the program.

Unapproved and/or off-label use disclosure

AffinityCE/MedAll requires CE faculty to disclose to the participants:

When products or procedures being discussed are off-label, unlabeled, experimental, and/or investigational (not US Food and Drug Administration [FDA] approved); and
Any limitations on the information presented, such as data that are preliminary or that represent ongoing research, interim analyses, and/or unsupported opinion.

CME Inquiries

For all CME policy-related inquiries, please contact us at ce@affinityced.com.

Participation Costs

There is no cost to participate in this program.

This continuing education activity is active starting February 27th 2026 and will expire on December 31st 2026.

Estimated time to complete this activity: 15 minutes.

Learning objectives

Upon completion of this activity, participants should be better able to:

Interpret emerging clinical evidence on Factor XIa inhibition - including findings from PACIFIC-STROKE and ongoing Phase III studies such as OCEANIC-STROKE and LIBREXIA-STROKE - to inform treatment decisions in non-cardioembolic stroke.

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Computer generated transcript

Warning!
The following transcript was generated automatically from the content and has not been checked or corrected manually.

Hello, everyone. I'm Doctor Jeffrey Saber, a professor of neurology at UCLA and I'll be talking in this brief program about applying evidence-based antithrombotic strategies for secondary stroke prevention. Here are my disclosures. The objective of this presentation is to help you implement evidence-based antithrombotic strategies for secondary prevention following non-cardimbolic ischemic stroke or TIA as outlined in the recently issued American Heart Association guideline recommendations, and with additional insights from contemporary trials. To motivate things, let's start off with a polling question. In patients with minor non-cardiollic ischemic stroke or high-risk TIA who present within 24 hours and have no contraindications, which antithrombotic strategy would you recommend to reduce early recurrent stroke risk? And you can see the five strategies below, they're kind of wordy, so I'll let you read through them and give you a chance to give an answer. All right. Now, let's go ahead and we'll cover the material that provides the answer for that in a case-based way. We're gonna have 3 motivating cases today. This is the first Ms. Jones, who's a 68 Caucasian woman who presented with right-sided numbness affecting the face, arm, And leg and no other deficits. Uh, and that stroke scale was 2. She does have a background medical history of hypertension, hyperlipidemia, and diabetes. And she was on no antithrombiotics prior to presenting with this stroke. And you can see on the MRI scan, on the right, the DWI shows a Abnormality in the ventral postolateral portion of the thalamus where a pure sensory stroke will occur from a small lacunar infarct. Diagnostic workup in Ms. Jones followed the usual workup for causes in ischemic stroke patients by imaging the blood vessels in the aorta, head, and neck. Doing coagulation labs for the clotting system, looking for structural cardiac disease with echocardiography, and looking for cardiac dysrhythmias with cardiac telemetry. And in Ms. Jones, Three of these were completely normal. There was some left ventricular hypertrophy seen on her echo consistent with her hypertension, but that is not a cause of stroke directly. So, um, the, uh, this suggests that she had, uh, through lacunar stroke due to intrinsic occlusions in small vessels from microaertherosclerosis or lipohadeosis too small to see. So, What should be done for the antithrombotic therapy in this patient. And the new guidelines from the AHA recommend double antiplatelet therapy or DPPT for 21 days, and then single antiplatelet therapy thereafter or SAPT. When the patient presents with a minor ischemic stroke, as here, and a stroke scale less than 3, that is non-cardiembolic. Or a non-cardibolic high-risk TIA and they've not received intravenous thrombolysis. Uh, in, uh, these patients at lower risk for hemorrhagic transformation and high risk for ischemic stroke, starting with uh double antiplatelet therapy for the first high-risk 21 days is recommended. And stronger evidence exists for the combination of aspirin and clopidogrel. Uh, Uh, a, as a first-line option, aspirin and ticagrelor is also recognized as a first-line option, but may have a little bit more complications, so it does not have a strong a recommendation. Why are we using antiplatelet agents in this setting for non-cardibolic stroke? And the classic view is shown here that uh in patients with atherosclerotic intrusions into the lumen, as in the top, uh, that causes this laminar high-speed flow over the irregular surface of the atherosclerotic plaque. Precipitating platelet activation and aggregation and platelet-rich thrombi. Uh, for those, antiplatelet therapy is preferred. In contrast, for cardiomembolic stroke, most forms, uh, such as atrial fibrillation, it due to stasis in the atrium, low flow, and whenever blood isn't flowing, it tends to clot through the coagulation system, forming red clots, erythrocyte rich. Um, and there where the clotting protein cascade is the driver anticoagulant mech uh, Anticoagulant medications are preferred. In thinking about the antiplatelet agents for patients with non-carbolic stroke, here is a schema of the platelet showing the site of action of our major classes, uh, aspirin, the COX-1 inhibitor, uh, Clopidogrel, ticagrelor, and others as uh PGY2 inhibitors, the GP2-3 blockers, and phosphodiesterase inhibitors. Now, where does the 21 day recommendation for intensive depth come from? It's driven in part by the fact that under standard therapy in patients with non-cardimolic stroke, the risk of recurrence is very front-loaded, as you see here. It is tremendously high in the 1st 3 weeks, still somewhat high between 3 weeks and 3 months, and then medium ongoing risk thereafter. So, uh, the trials that looked at, uh, clopidogrel and aspirin versus aspirin alone, DAT versus single aspirin were the chance and point trials. And here, you can see, uh, that the patients who had clopidogrel and aspirin were less likely to have a stroke than aspirin alone. And Essentially, all of the benefit of the double therapy occurred in the 1st 3 weeks. If we pull the data from these trials, the double antiplatelet therapy reduces the recurrence in the first three weeks from 6.3% to 4.4%. Uh, however, as you see in the graph, after, um, the major ischemic events cluster early, and then, uh, become low, whereas the bleeding episodes and double antiplatelet therapy will increase the bleeding risk over single antiplatelet therapy remains, uh, modestly elevated throughout the time of therapy. So the Benefit in reducing ischemic stroke versus the cost of increasing hemorrhage, clearly worth undertaking in the 1st 3 weeks, and then it's not clearly beneficial, so the switch to single antiplatelet therapy occurs. The guidelines did have this very nice, very detailed algorithm. Uh, I advise people to have it handy. You start with the non-chombolic stroke or TIA, and you see they're under 24 hours, didn't get TPA minor deficit, that puts you to clopidogrel and aspirin for the 1st 21 days for Ms. Jones. OK, let's turn To case two, Mr. Smith, who's a 72-year-old Asian man who presents with isolated right arm weakness, an anti-stroke scale of 3, history of high BP and tobacco use, and was taking aspirin prior to the event. And on the clearar MRI to the right, you can see abnormality in the motor strip right at the hand knob, affecting just the arm. The workup in Mr. Smith found a normal echocardiogram, no atrial fibrillation, but two relevant other findings. On the vessel imaging, there was 60% stenosis of the intracranial left internal carotid siphon, um, not in the neck, not operable, but severe afro there, symptomatic large artery afro. And on coagulation testing,