ISCHEMIC STROKE

Prevention of ischemic stroke

David Goldemund M.D.
Updated on 04/06/2024, published on 02/02/2024

primary stroke prevention – interventions and measures taken to reduce the risk of stroke in asymptomatic individuals
secondary stroke prevention – interventions taken to reduce the risk of recurrent ischemic stroke in individuals who have already suffered a stroke or TIA; the treatment is based on the cause of the previous ischemic stroke and takes into account individual vascular risk factors

Stroke prevention involves:

initial vascular risk stratification (to assess an individual’s likelihood of experiencing a cardiovascular event) – analyze risk factors + personal medical history (including prior stroke or another cardiovascular event)
- SCORE2 (Systematic COronary Risk Evaluation) – a risk stratification tool used primarily in Europe to estimate the 10-year risk of fatal atherosclerotic cardiovascular disease (CVD), including stroke
- Framingham Risk Score (focuses on the risk of coronary disease)
- ASCVD (Atherosclerotic Cardiovascular Disease) Risk Calculator – used for primary prevention
- CHA₂DS₂-VASc Score (risk of stroke in patients with atrial fibrillation)
management of vascular risk factors
antithrombotic therapy
- antiplatelet agents – aspirin, clopidogrel, ticagrelor, or their combinations (DAPT) are commonly prescribed
  - SAPT or short-term DAPT followed by SAPT
  - SAPT + low-dose anticoagulants in selected patients
- anticoagulants – for those with cardioembolic risk factors (most commonly atrial fibrillation) or significant thrombophilia
surgical and endovascular procedures
- carotid endarterectomy or angioplasty with stenting on extracerebral and cerebral arteries
- PFO closure, LAA closure, pulmonary AV shunt occlusion, RF ablation, cardiac surgery, etc.
regular monitoring and strict adherence to treatment are crucial

Vascular risk factors

For an overview of vascular risk factors, see here and here

Cardiovascular disease risk predictors

SCORE2 → calculator
ASCVD (Atherosclerotic Cardiovascular Disease) Risk Calculator

Dyslipidemia

Arterial hypertension (HTN)

arterial hypertension
overview of oral antihypertensive agents

Cardioembolic strokes

Other risk factors

smoking
diabetes mellitus
sleep apnea syndrome
hyperhomocysteinemia
oral contraceptives
elevated hs-CRP

Antiplatelet and anticoagulant therapy

Antiplatelet therapy

Anticoagulant therapy

Anticoagulant therapy – overview
- Warfarin
- Low Molecular Weight Heparins (LMWHs)
- Direct Oral Anticoagulants (DOACs)
  - Dabigatran (PRADAXA)
  - Apixaban (ELIQUIS)
  - Rivaroxaban (XARELTO)
  - Edoxaban (LIXIANA)
- Reduced-dose DOACs
Timing of anticoagulant therapy
Risk and prevention of bleeding in anticoagulant therapy
Neutralization of the anticoagulant effects
Perioperative and Periprocedural Management of Anticoagulant Therapy

Specific situations

Preventive interventional procedures

Carotid endarterectomy (CEA)

Angioplasty and stenting

Preventive cardiologic procedures

Novel and experimental approaches

Anti-XI inhibitors

Factor XIa inhibitors are a novel class of anticoagulants that target factor XI, a component of the intrinsic coagulation pathway. While they have primarily been investigated for their potential to prevent venous thromboembolism (VTE) and reduce the risk of thrombosis without increasing the risk of bleeding, there is emerging interest in their role in cardiovascular prevention, including stroke prevention

milvexian is a peroral factor XIa inhibitor
- AXIOMATIC-SSP – milvexian, added to dual antiplatelet therapy, did not substantially reduce the composite outcome of symptomatic ischemic stroke and did not meaningfully increase the risk of major bleeding
- ongoing stroke trial LIBREXIA (placebo-controlled study to demonstrate the efficacy and safety of milvexian in addition to single or dual antiplatelet therapy for stroke prevention after an acute ischemic stroke or high-risk TIA)
osocimab
ibisomab

Anti-inflammatory drugs

Inflammation plays a significant role in the development and progression of atherosclerosis

colchicine
- by targeting inflammation, colchicine may help reduce the inflammatory burden on blood vessels, potentially slowing the progression of atherosclerosis and reducing the risk of stroke
- the CLEAR trial investigated the effect of colchicine on markers of inflammation and lipid profile in patients with a history of ischemic stroke/TIA. While the primary endpoints were changes in inflammatory markers and lipid profile, the study also reported a reduction in recurrent vascular events, including stroke, in patients treated with colchicine compared to placebo
- preliminary results of CONVINCE trial – colchicine failed to show significant benefit in the treatment of patients with non-cardioembolic ischemic stroke in the primary analysis; however, the results did reveal a significant reduction in recurrent stroke and cardiovascular events in the per-protocol analysis and in the subgroup of patients with coronary artery disease
beyond colchicine, other anti-inflammatory agents and interventions targeting specific inflammatory pathways are being studied for their potential to reduce inflammation-related stroke risk
- interleukin-1 (IL-1) inhibitors (canakinumab and anakinra)
- tumor necrosis factor-alpha (TNF-α) inhibitors (such as infliximab and etanercept)
- P-selectin inhibitors (inclacumab and crizanlizumab)
  - P-selectin is a cell adhesion molecule involved in the recruitment of leukocytes to sites of inflammation
- CCR2 inhibitors
  - chemokine receptor 2 (CCR2) is involved in the recruitment of monocytes to sites of inflammation
- low-dose methotrexate (CIRT trial)