Key Clinical Summary: Etiology-Driven Secondary Stroke Prevention & the Emerging Role of Factor XIa Inhibitors

This is a micro-learning module summary of Dr. Andrew Demchuk's Secondary Stroke Prevention education session which you can find here. Before participating please read our CME and disclosure information which can be found here. This program was supported by an independent medical education grant from Bayer. This content is intended for US Healthcare Professionals only.

1 Why Etiology Matters

• Stroke remains a growing public-health crisis—7-13 million new events/year worldwide, with average first-year costs ≈ $50 000 and a projected doubling of incidence over the next two decades.
• Recurrence (~5 % at one year) is largely preventable when the cause is correctly identified and targeted.

2 Multidisciplinary Stroke-Prevention Clinics (MDT)

• Nurse-led, rapid-access clinics integrate stroke physicians, pharmacists, and rehabilitation staff to triage high-risk TIA/minor stroke, arrange urgent imaging, and provide a routine 3-month follow-up visit.
• MDTs improve adherence, close investigation gaps, and coordinate lifestyle and pharmacologic optimisation.

3 Etiology-Tailored Therapeutic Highlights

• Large-artery atherosclerosis
• Revascularise carotid or other critical stenoses early.
• Intensify LDL lowering to < 1.8 mmol/L
• Small-vessel disease (lipohyalinosis)
• Target systolic BP < 130 mm Hg and optimise type 2 diabetes control (e.g. GLP-1 RA).
• Cardio-embolic sources
• Non-valvular AF: DOACs preferred; combine DOAC + clopidogrel (omit aspirin) for patients needing stents (AUGUSTUS paradigm).
• Rheumatic AF or mechanical valves: remain on warfarin (INVICTUS).
• LV thrombus: DOACs appear at least as safe as VKAs (No-LVT)
• Cancer-associated coagulopathy
• Suspect when DWI shows small, multi-territory hits and D-dimer > 3 µg/mL—recurrence risk up to 40 % at 30 days; treat with LMWH or DOAC, individualising for GI/GU tumours.
• Patent Foramen Ovale (age < 60 y)
• Screen with TCD bubble, which has a three-fold higher yield for large shunts than transthoracic echo; close when large shunt and no alternate cause.
• Embolic Stroke of Uncertain Source (ESUS)
• Default to aspirin; pursue prolonged rhythm monitoring and cardiac MRI if initial work-up unrevealing; ESUS cohorts are now enrolled in Factor XIa trials (see below).
• Unusual arteriopathies (e.g., carotid web, FMD)
• Recognise shelf-like carotid defects on CTA; consider anticoagulation or surgical removal after recurrence despite DAPT.

4 Emerging Therapy – Factor XIa Inhibitors

• Target the intrinsic coagulation pathway, aiming to reduce thrombosis with minimal haemostatic compromise.
• Phase III programmes (PACIFIC-Stroke, OCEANIC, Librexia) include large-artery and ESUS populations; results expected within 18-36 months.
• These agents may serve as an add-on or alternative to current antithrombotics.

5 Key Take-Home Messages

• Aetiology-driven care, delivered through MDT stroke-prevention clinics, is central to reducing recurrent events and healthcare costs.
• Follow a structured, time-linked diagnostic pathway; stop when a convincing cause is found, but dig deeper (cancer, PFO, ESUS) when it is not.
• Match therapy to the cause
• Factor XIa inhibitors hold promise as the next leap forward in secondary prevention—stay tuned and consider trial participation.

By embedding these evidence-based strategies into everyday practice, clinicians can meaningfully curb the rising global burden of stroke recurrence.