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neuro.stroke-laa.v1PRODUCTION
neuro.stroke-laa.v1

Large-Artery Atherosclerotic Stroke (TOAST LAA)

neurologyacutechronicadult
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12/12 authored

Canonical 12-phase frame with authored status for this dossier.

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Detailed

Ischemic stroke with LAA mechanism — carotid ≥50%, intracranial atherosclerosis, vertebrobasilar atheroma, aortic arch atheroma, or CABG-related atheroembolism (AHA/ASA 2021)

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LAA mechanism flagged or being investigated

Patient inputs (15)

Age stratifies CEA vs CAS choice (CREST — older patients benefit more from CEA; younger from CAS); affects bleed risk of intensive statin/DAPT (AHA/ASA 2021)

eGFR for contrast CTA/CTP and SAMMPRIS DAPT bleed-risk assessment

Active smoking accelerates atherosclerosis; cessation pharmacotherapy per AHA/ASA 2021 Class I

High-intensity statin target LDL <55 mg/dL post-LAA stroke (2026 ACC/AHA Lipid; SPARCL PMID 16899775); LDL >100 mandates intensification

NASCET measurement of ipsilateral carotid stenosis drives CEA/CAS decision (AHA/ASA 2021 Class I)

Intracranial vessel patency for SAMMPRIS eligibility (Chimowitz NEJM 2011 PMID 21507093); vertebrobasilar atheroma detection

Confirms ischemic territory + borderzone pattern (perfusion failure phenotype) supporting LAA mechanism (AHA/ASA 2021)

TIA vs minor stroke vs major stroke — qualifying event for SAMMPRIS / NASCET defines treatment window (≤14 d for CEA/CAS per AHA/ASA 2021 Class I)

CEA/CAS within 14 d of symptomatic event maximises benefit per NASCET / pooled European Carotid Surgery Trial (AHA/ASA 2021 Class I)

Target BP <130/80 long-term per AHA/ASA 2021 + 2025 AHA/ACC HTN secondary prevention; avoid SBP <120 in critical bilateral carotid stenosis (perfusion pressure)

Existing antithrombotic on board drives DAPT initiation decision (SAMMPRIS DAPT × 90 d adds clopidogrel to aspirin); avoid triple therapy

Identifies complex aortic arch atheroma ≥4 mm — under-recognised LAA source (Amarenco 1994; ARCH 2014)

Prior carotid intervention reframes anatomy + restenosis surveillance pathway (AHA/ASA 2021)

APOL1 variant + African American ancestry — emerging signal for accelerated atherosclerosis + CKD-stroke overlap (research-grade)

Glycemic control HbA1c <7% reduces atherosclerotic progression (ADA 2026; AHA/ASA 2021)

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Severity triggers (8)

8 need judgement
  • informationallife_threateningsymptomatic_carotid_70_99pct_critical
    Symptomatic carotid stenosis 70-99% (near-occlusion) — highest event-rate phenotype; expedite intervention within 48 h-7 d (AHA/ASA 2021 Class I)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresymptomatic_carotid_stenosis_ge_50pct
    Symptomatic carotid stenosis ≥50% ipsilateral on NASCET measurement → CEA/CAS within 14 d (AHA/ASA 2021 Class I)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereintracranial_atherosclerosis_mad_aspirin_dapt
    Intracranial atherosclerosis 70-99% (MAD — Mod-Adv Disease) on vessel-wall MRI or hi-res CTA — SAMMPRIS DAPT × 90 d + intensive statin (NOT stenting per SAMMPRIS)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverevertebral_basilar_atheroma
    Vertebrobasilar atheroma — posterior circulation LAA phenotype; often underdiagnosed; HINTS central features + posterior infarct on DWI
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereaortic_arch_atheroma
    Complex aortic arch atheroma ≥4 mm or mobile component on TEE — often missed source of LAA stroke (Amarenco NEJM 1994 PMID 8035879)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverecabg_related_atherosclerotic_stroke
    Recent CABG / vascular endovascular procedure → atheroembolic LAA stroke from manipulation of atheromatous aortic arch (AHA/ASA 2021)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatestenting_vs_endarterectomy_crest
    CEA vs CAS decision — CREST showed equivalent composite outcomes but stroke favours CEA (esp ≥70 yo) and MI favours CAS (Brott NEJM 2010 PMID 20505173)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateapol1_overlap_aa
    APOL1 risk variant + African American ancestry — emerging signal for accelerated atherosclerosis + CKD-stroke overlap; recognise as high-risk phenotype (research-grade signal)
    Trigger could not be auto-evaluated — needs clinician judgement.

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RISK_STRATIFICATIONrequiredDrives severity classification
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Recommended regimen

LAA secondary prevention bundle (AHA/ASA 2021): statin + antiplatelet (with SAMMPRIS DAPT for ICAD) + BP + glycemic + smoking cessation ± CEA/CAS
axis: laa_secondary_preventionstep 1 - Step 1 — High-intensity statin (immediate, lifelong)
Selected step "Step 1 — High-intensity statin (immediate, lifelong)" — All confirmed LAA-mechanism patients regardless of LDL (PCSK9-anchored 2026 ACC/AHA Lipid LDL <55 target)
  • atorvastatin
    first line
    HMG_CoA_reductase_inhibitor
    80 mg PO daily • PO • once daily
    triggers: laa_mechanism_confirmed
    SPARCL (Amarenco NEJM 2006 PMID 16899775) — high-dose atorvastatin reduces recurrent stroke ~16%; 2026 ACC/AHA Lipid LDL <55 post-stroke
    rxcui 83367
  • rosuvastatin
    first line
    HMG_CoA_reductase_inhibitor
    20-40 mg PO daily • PO • once daily
    triggers: atorvastatin_intolerance
    Alternative high-intensity statin (2026 ACC/AHA Lipid)
    rxcui 301542
  • ezetimibe
    add on
    cholesterol_absorption_inhibitor
    10 mg PO daily • PO • once daily
    triggers: ldl_>55_on_max_statin
    IMPROVE-IT — driving LDL toward <55 target (2026 ACC/AHA Lipid)
    rxcui 341248

outpatient playbook — drug actions (6)

  1. 1. atorvastatin
    80 mg PO daily • PO • once daily
    trigger: All LAA patients; LDL ≥55
    2026 ACC/AHA Lipid LDL <55
  2. 2. aspirin 81 mg daily (post-DAPT taper at day 90 for SAMMPRIS arm)
    81 mg PO daily • PO • once daily
    trigger: Day 90 post-SAMMPRIS OR baseline non-ICAD LAA
    AHA/ASA 2021 long-term antiplatelet for non-cardioembolic stroke
  3. 3. cilostazol (refractory ICAD)
    100 mg PO BID • PO • BID
    trigger: Recurrent event on DAPT or progressive ICAD lesions
    CSPS.com — add-on antiplatelet for non-cardioembolic stroke
  4. 4. rivaroxaban 2.5 BID + aspirin (COMPASS)
    Rivaroxaban 2.5 mg BID + ASA 81 mg daily • PO • BID + daily
    trigger: Stable polyvascular LAA (≥30 d post-event) + PAD or CAD + low bleed risk
    COMPASS (Eikelboom NEJM 2017) — reduces MACE incl stroke in stable atherosclerosis
  5. 5. lisinopril ± chlorthalidone ± amlodipine
    Per BP target • PO • daily
    trigger: BP ≥130/80
    PROGRESS PMID 11589932; 2025 AHA/ACC HTN
  6. 6. varenicline / NRT / bupropion
    Per agent • PO / patch / lozenge • per agent
    trigger: Active tobacco use
    AHA/ASA 2021 Class I

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Cortical / borderzone infarct pattern suggesting LAA mechanism (AHA/ASA 2021 PMID 34024117); Carotid stenosis ≥50% ipsilateral on CTA/MRA/duplex (NASCET measurement; AHA/ASA 2021 Class I); Intracranial atherosclerosis on vessel-wall MRI or hi-res CTA (SAMMPRIS Chimowitz NEJM 2011 PMID 21507093).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Large-Artery Atherosclerotic Stroke (TOAST LAA)** (neuro.stroke-laa.v1).
Phenotype framing: LAA sub-phenotype: symptomatic carotid ≥50% vs critical 70-99% vs intracranial MAD (Mod-Adv Disease) SAMMPRIS-eligible vs vertebrobasilar vs aortic arch vs CABG-related (AHA/ASA 2021; SAMMPRIS Chimowitz NEJM 2011)
Scope: Ischemic stroke with LAA mechanism — carotid ≥50%, intracranial atherosclerosis, vertebrobasilar atheroma, aortic arch atheroma, or CABG-related atheroembolism (AHA/ASA 2021)

No severity triggers fired against current inputs.

Plan

Regimen axis: **LAA secondary prevention bundle (AHA/ASA 2021): statin + antiplatelet (with SAMMPRIS DAPT for ICAD) + BP + glycemic + smoking cessation ± CEA/CAS** — step "Step 1 — High-intensity statin (immediate, lifelong)".
1. atorvastatin 80 mg PO daily PO once daily (HMG_CoA_reductase_inhibitor, first line) — SPARCL (Amarenco NEJM 2006 PMID 16899775) — high-dose atorvastatin reduces recurrent stroke ~16%; 2026 ACC/AHA Lipid LDL <55 post-stroke
2. rosuvastatin 20-40 mg PO daily PO once daily (HMG_CoA_reductase_inhibitor, first line) — Alternative high-intensity statin (2026 ACC/AHA Lipid)
3. ezetimibe 10 mg PO daily PO once daily (cholesterol_absorption_inhibitor, add on) — IMPROVE-IT — driving LDL toward <55 target (2026 ACC/AHA Lipid)

Setting playbook (outpatient) — Stroke clinic 7-14 d + 90 d + 12 mo: LDL <55, BP <130/80, HbA1c <7%, smoking cessation, DAPT taper at day 90 for SAMMPRIS, carotid surveillance post-CEA/CAS, vascular cognitive impairment screen (AHA/ASA 2021)
4. atorvastatin 80 mg PO daily PO once daily — All LAA patients; LDL ≥55 (2026 ACC/AHA Lipid LDL <55)
5. aspirin 81 mg daily (post-DAPT taper at day 90 for SAMMPRIS arm) 81 mg PO daily PO once daily — Day 90 post-SAMMPRIS OR baseline non-ICAD LAA (AHA/ASA 2021 long-term antiplatelet for non-cardioembolic stroke)
6. cilostazol (refractory ICAD) 100 mg PO BID PO BID — Recurrent event on DAPT or progressive ICAD lesions (CSPS.com — add-on antiplatelet for non-cardioembolic stroke)
7. rivaroxaban 2.5 BID + aspirin (COMPASS) Rivaroxaban 2.5 mg BID + ASA 81 mg daily PO BID + daily — Stable polyvascular LAA (≥30 d post-event) + PAD or CAD + low bleed risk (COMPASS (Eikelboom NEJM 2017) — reduces MACE incl stroke in stable atherosclerosis)
8. lisinopril ± chlorthalidone ± amlodipine Per BP target PO daily — BP ≥130/80 (PROGRESS PMID 11589932; 2025 AHA/ACC HTN)
9. varenicline / NRT / bupropion Per agent PO / patch / lozenge per agent — Active tobacco use (AHA/ASA 2021 Class I)

Non-pharmacologic actions:
- AHA "Get With The Guidelines" outcome documentation — mRS, statin, BP, antithrombotic, smoking cessation, AF screen done
- Recurrent-stroke counselling — any focal deficit = 911
- Sleep study if STOP-BANG ≥3
- Mediterranean diet (PREDIMED) + aerobic 150 min/wk
- Vascular surgery follow-up if CEA/CAS performed

AVOID / contraindication checks:
- SAMMPRIS_DAPT_capped_at_90_days_to_limit_bleeding (Chimowitz NEJM 2011 PMID 21507093)
- CEA_or_CAS_within_14d_of_symptomatic_event (AHA/ASA 2021 Class I; NASCET)
- Avoid_SBP_<120_in_critical_bilateral_carotid_stenosis (perfusion pressure dependent)
- Cilostazol_contraindicated_in_HF_NYHA_III_IV
- COMPASS_regimen_avoid_in_high_bleeding_risk_or_chronic_DAPT_indication (Eikelboom NEJM 2017)
- High_intensity_statin_baseline_LFTs_repeat_at_4 6wk (2026 ACC/AHA Lipid)
- Varenicline_caution_in_severe_psych_history (AHA/ASA 2021)

Monitoring

Regimen monitoring:
- LDL at 4-6 wk after statin start; q6-12 mo thereafter; target <55 (2026 ACC/AHA Lipid)
- BP home log + clinic q3 mo until <130/80; then q6 mo (2025 AHA/ACC HTN)
- Carotid duplex at 6 wk + 6 mo + annually post CEA/CAS (AHA/ASA 2021)
- HbA1c q3 mo if DM until <7%, then q6 mo (ADA 2026)
- Bleed surveillance on DAPT (CBC, stool guaiac if symptoms; cap at 90 d per SAMMPRIS)
- Annual MoCA for vascular cognitive impairment screen (AHA/ASA 2021)
- Smoking status every visit + reinforcement (AHA/ASA 2021 Class I)

Setting (outpatient) monitoring:
- Clinic visit at 7-14 d for medication reconciliation
- Stroke clinic 90 d + 12 mo
- LDL at 4-6 wk after statin then q6-12 mo (target <55)
- BP home log + clinic q3 mo (target <130/80)
- HbA1c q3 mo until controlled then q6 mo
- Carotid duplex post-CEA/CAS 6 wk + 6 mo + annually
- PHQ-9 + MoCA at 90 d, 6 mo, 12 mo

Follow-up plan: Stroke clinic 7-14 d + 90 d + 12 mo: LDL <55, BP <130/80, HbA1c <7%, antithrombotic adherence, smoking cessation, carotid surveillance (AHA/ASA 2021)
- Close-out criterion: Secondary prevention bundle on board + carotid surveillance scheduled

Monitoring phase: Inpatient telemetry; carotid duplex post-CEA at 6 wk + 6 mo + annually; LFTs/CK on statin; bleed surveillance on DAPT (SAMMPRIS 90-d cap to limit bleed signal) (AHA/ASA 2021)

Disposition

Current setting: outpatient — Stroke clinic 7-14 d + 90 d + 12 mo: LDL <55, BP <130/80, HbA1c <7%, smoking cessation, DAPT taper at day 90 for SAMMPRIS, carotid surveillance post-CEA/CAS, vascular cognitive impairment screen (AHA/ASA 2021)

Disposition criteria:
- Continue lifelong secondary prevention — no de-escalation of antithrombotic / statin (AHA/ASA 2021)
- Transition to community exercise programs at 6-12 mo per functional status

Escalation triggers (move to higher acuity):
- New TIA-spectrum / focal deficit → ED
- LDL >55 on max statin → ezetimibe + PCSK9i (2026 ACC/AHA Lipid)
- BP >140/90 on 3-drug regimen → resistant HTN workup (cardio.htn.resistant.v1)
- Restenosis on carotid duplex → vascular surgery re-evaluation
- Recurrent event on DAPT → cilostazol or COMPASS add-on

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Symptomatic carotid stenosis 70-99% (near-occlusion) — highest event-rate phenotype; expedite intervention within 48 h-7 d (AHA/ASA 2021 Class I)
- [SEVERE] Symptomatic carotid stenosis ≥50% ipsilateral on NASCET measurement → CEA/CAS within 14 d (AHA/ASA 2021 Class I)
- [SEVERE] Intracranial atherosclerosis 70-99% (MAD — Mod-Adv Disease) on vessel-wall MRI or hi-res CTA — SAMMPRIS DAPT × 90 d + intensive statin (NOT stenting per SAMMPRIS)

Citations

- 2021 AHA/ASA Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack + 2025 AHA/ACC HTN + 2026 ACC/AHA Dyslipidemia + ADA 2026 [PMID:34024117](https://pubmed.ncbi.nlm.nih.gov/34024117/)
- Cited evidence (PMID 16899775) [PMID:16899775](https://pubmed.ncbi.nlm.nih.gov/16899775/)
- Cited evidence (PMID 20505173) [PMID:20505173](https://pubmed.ncbi.nlm.nih.gov/20505173/)
- Cited evidence (PMID 7477192) [PMID:7477192](https://pubmed.ncbi.nlm.nih.gov/7477192/)
- Cited evidence (PMID 21507093) [PMID:21507093](https://pubmed.ncbi.nlm.nih.gov/21507093/)

Last reconciled with current guidelines: 2026-05-15.
References
  • 2021 AHA/ASA Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack + 2025 AHA/ACC HTN + 2026 ACC/AHA Dyslipidemia + ADA 2026 — PMID:34024117
  • Cited evidence (PMID 16899775) — PMID:16899775
  • Cited evidence (PMID 20505173) — PMID:20505173
  • Cited evidence (PMID 7477192) — PMID:7477192
  • Cited evidence (PMID 21507093) — PMID:21507093