Ischemic stroke medical therapy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Hasnain Ali Moryani, MBBS[2] Aysha Anwar, M.B.B.S[3]
Overview
Overview
- Acute ischemic stroke therapy is primarily directed toward rapid reperfusion with intravenous thrombolysis (alteplase or tenecteplase) in eligible patients and endovascular thrombectomy (EVT) in eligible patients with large vessel occlusion (LVO); these treatments should be considered in parallel and should not delay each other.[1]
- Tenecteplase (0.25 mg/kg IV bolus; max 25 mg) is now recommended as an equivalent alternative to alteplase (0.9 mg/kg; max 90 mg) for IV thrombolysis within 4.5 hours of symptom onset, based on multiple large randomized controlled trials demonstrating noninferiority with the practical advantage of single-bolus administration.[2][3][4]
- Antiplatelet therapy (usually aspirin) is recommended within 24–48 hours after onset in most patients who are not receiving IV thrombolysis, and is generally delayed until 24 hours after thrombolysis. Short-term dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel for 21 days is recommended for minor noncardioembolic ischemic stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4).
- For patients with atrial fibrillation-related stroke, early initiation of direct oral anticoagulants (DOACs) within 4 days is supported by the CATALYST individual patient data meta-analysis (n=5441), which demonstrated reduced recurrent ischemic stroke (OR 0.66, 95% CI 0.45–0.96) without increased symptomatic intracerebral hemorrhage.[5]
- Secondary prevention includes antiplatelets or anticoagulation depending on etiology, statin therapy (target LDL-C <70 mg/dL for atherosclerotic stroke), and blood pressure management.[6][7]
Medical Therapy
Medical Therapy
Initial Management
- Treatment of COVID-19–associated ischemic stroke generally follows standard acute ischemic stroke pathways.
- In patients with suspected or confirmed LVO, evaluation for EVT should occur urgently, and IV thrombolysis should be given when eligible without delaying EVT.
- EVT indications include appropriately selected patients within 0–6 hours, and in selected patients within 6–24 hours based on imaging/clinical criteria; recent randomized trials also support EVT in selected large ischemic core anterior circulation strokes (ASPECTS 3–5) and basilar artery occlusion.[8][9][10]
- The usefulness of anticoagulants such as thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) is not well established in the acute setting of stroke.[11]
- The use of thrombolysis via ultrasound waves concomitant to IV fibrinolysis is not recommended.[12]
Medical Therapy
Alteplase
- IV alteplase (0.9 mg/kg, maximum dose 90 mg over 60 min, with 10% of the dose given as a bolus over 1 min) is recommended for selected patients who can be treated within 3–4.5 hours of ischemic stroke symptom onset or patient last known well or at baseline state.[13][14][15]
- In imaging-selected patients with wake-up stroke/unknown onset or extended-window presentations, IV thrombolysis may be beneficial when selection criteria are met (eg, DW-MRI lesion smaller than one-third of the MCA territory with no visible signal change on FLAIR).[16]
- IV alteplase should be initiated as soon as possible, having been demonstrated to produce better outcomes the sooner it is administered. The number needed to treat (NNT) for one additional patient with excellent functional outcome (mRS 0–1) is 10 within 3 hours and 19 from 3–4.5 hours.
- Hyperglycemia should be treated during the first 24 hours after ischemic stroke, to achieve values of 140 to 180 mg/dL. Intensive glucose control (80–130 mg/dL) with IV insulin is not recommended (COR 3: No Benefit).
- IV alteplase may cause bleeding and angioedema.
- Glycoprotein IIb/IIIa inhibitors (tirofiban, apiximab, eptifibatide) should not be coadministered with IV alteplase.[17]
- IV alteplase may be used in patients under warfarin if the INR is lower than 1.7.
- IV alteplase should not be administered to patients who have received a full dose of low-molecular-weight heparin within the previous 24 hours (including prophylactic doses).[18]
- In case of intracranial bleeding due to alteplase administration, alteplase should be suspended, blood draws should be taken (CBC, coagulation studies), tranexamic acid should be administered (1000 mg IV infused over 10 min), and a subsequent non-contrasted CT scan of the head obtained.[19]
- The use of IV alteplase should be used cautiously in patients who have undergone a major surgery in the past 2 weeks.
- IV alteplase for ischemic stroke is contraindicated in patients with a severe head trauma or subarachnoid hemorrhage in the preceding 3 months.
Tenecteplase
- Tenecteplase (0.25 mg/kg IV bolus; max 25 mg) is recommended as an equivalent alternative to alteplase for IV thrombolysis in eligible acute ischemic stroke patients presenting within 4.5 hours of symptom onset (COR 1, 2026 AHA/ASA). Tenecteplase received FDA approval for acute ischemic stroke in 2025.[20]
- Multiple large phase III randomized controlled trials (AcT, n=1600; ATTEST-2, n=1777; ORIGINAL, n=1465; TRACE-2, n=1430) have individually demonstrated noninferiority of tenecteplase 0.25 mg/kg versus alteplase for the primary outcome of mRS 0–1 at 90 days, with similar safety profiles:
- AcT: risk difference 2.1% (95% CI, −2.6 to 6.9)
- ATTEST-2: risk difference 1.99% (95% CI, −2.77 to 6.75)
- ORIGINAL: adjusted risk difference 2.12% (95% CI, −2.17 to 6.40)
- A systematic review and meta-analysis of 11 RCTs demonstrated that tenecteplase was superior to alteplase for excellent functional outcome (mRS 0–1) with similar rates of symptomatic intracerebral hemorrhage and mortality.[21]
- Tenecteplase at a dose of 0.40 mg/kg is not recommended due to no additional benefit and potential for harm (COR 3: Harm).
- Among patients with LVO planned for thrombectomy, tenecteplase (0.25 mg/kg) achieved higher early reperfusion than alteplase (22% vs 10%) and improved 90-day functional outcome (median mRS 2 vs 3) with similar symptomatic ICH (1% vs 1%) in EXTEND-IA TNK.[22]
- Tenecteplase has also shown benefit in selected patients treated 4.5–24 hours after onset when thrombectomy is not available, in patients with salvageable ischemic penumbra on perfusion imaging (TRACE-III).[23]
| Thrombolytic Agent | Dose | Administration | Key Evidence |
|---|---|---|---|
| Alteplase | 0.9 mg/kg (max 90 mg) | 10% bolus over 1 min, remainder infused over 60 min | Standard of care since 1995; NNT 10 within 3 h, NNT 19 from 3–4.5 h |
| Tenecteplase | 0.25 mg/kg (max 25 mg) | Single IV bolus over 5–10 seconds | Noninferior to alteplase in AcT, ATTEST-2, ORIGINAL, TRACE-2; FDA approved 2025 |
| Tenecteplase 0.4 mg/kg | Not recommended — no additional benefit and potential for harm (COR 3: Harm) | ||
Endovascular Thrombectomy
- EVT is recommended for patients with AIS from anterior circulation proximal LVO (ICA or M1), presenting within 6 hours from onset, with NIHSS score ≥6, prestroke mRS 0–1, and ASPECTS 3–10 (COR 1).
- In selected patients with anterior circulation proximal LVO presenting between 6 and 24 hours, with age <80 years and appropriate imaging criteria, EVT is recommended.
- For patients with ASPECTS 0–2 within 6 hours (age <80 years), EVT may be considered in selected cases.
- The ATLAS individual patient data meta-analysis of 6 large-core trials confirmed EVT benefit up to core volume of 150 mL, with NNT of 4.2 for ≥1 mRS point improvement and NNT of 8.6 for functional independence. EVT recipients more than doubled their rate of functional independence compared with medical therapy alone (approximately 21% vs 9%).
- For patients with prestroke mRS of 2 presenting within 6 hours with NIHSS ≥6 and ASPECTS ≥6, EVT is reasonable (COR 2a).
Posterior Circulation
- In patients with AIS from basilar artery occlusion, baseline mRS 0–1, NIHSS ≥10, and PC-ASPECTS ≥6, EVT within 24 hours is recommended (COR 1), based on the ATTENTION and BAOCHE trials.
- The VERITAS individual patient data meta-analysis of 4 RCTs (BEST, BASICS, ATTENTION, BAOCHE) demonstrated EVT benefit for basilar artery occlusion (adjusted cOR 2.41, 95% CI 1.78–3.26) with reduced mortality (OR 0.60).[24]
IVT Before EVT
- In patients eligible for both IV thrombolysis and EVT, IV thrombolysis should be administered without delaying EVT. The IRIS meta-analysis demonstrated a time-dependent benefit of IVT before EVT, with significant benefit when onset-to-IVT time was short.[25]
- IV thrombolysis should not be withheld in EVT-eligible patients solely because EVT is planned, unless the patient is already in the angiography suite and EVT can be initiated immediately.
Antiplatelet Therapy
- Administration of aspirin isrecommended in patients with AIS within 24 to 48 hours after onset. For those treated with IV alteplase, aspirin administration is generally delayed until 24 hours later.[26]
- The dose of aspirin is usually between 160–325 mg daily.[27]
- IV aspirin administration within 90 minutes after the start of IV alteplase is associated with symptomatic intracerebral hemorrhage, for which co-administration is discouraged but benefits should be assessed in each individual case.[28]
- Aspirin should not substitute IV alteplase or mechanical thrombectomy in patients eligible for these therapies.
Dual Antiplatelet Therapy (DAPT)
- Dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel should be started early (ideally within 24 hours) and continued short term (commonly ~21 days) in patients with minor noncardioembolic ischemic stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4) who did not receive IV thrombolysis, followed by single antiplatelet therapy (SAPT).[29] The benefit of DAPT is confined to the first 21 days, as demonstrated by the CHANCE-POINT pooled analysis (HR 0.66, 95% CI 0.56–0.77).[30]
- In patients with recent stroke/TIA attributable to severe symptomatic intracranial stenosis (intracranial atherosclerotic disease, ICAD), DAPT for up to 90 days is reasonable.
- The INSPIRES trial extended the evidence for DAPT (aspirin + clopidogrel × 21 days) to patients with minor stroke (NIHSS ≤5) or TIA with presumed atherosclerosis presenting within 72 hours (NNT 53).[31]
| Trial | Population | DAPT Regimen | Duration | Key Result (NNT) |
|---|---|---|---|---|
| CHANCE | Minor stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4); within 24 h | Clopidogrel + aspirin | 21 days | Reduced recurrent stroke; NNT 28[32] |
| POINT | Minor stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4); within 12 h | Clopidogrel + aspirin | 90 days | Reduced ischemic events; NNT 67; stopped early for excess major bleeding[33] |
| THALES | Minor stroke (NIHSS ≤5) or high-risk TIA; within 24 h | Ticagrelor + aspirin | 30 days | Reduced stroke/death; NNT 91; increased fatal bleeding[34] |
| CHANCE-2 | CYP2C19 LOF carriers; minor stroke or TIA; within 24 h | Ticagrelor + aspirin | 21 days | Superior to clopidogrel + aspirin in LOF carriers; NNT 63[35] |
| INSPIRES | Minor stroke (NIHSS ≤5) or TIA with presumed atherosclerosis; within 72 h | Clopidogrel + aspirin | 21 days | Reduced recurrent stroke; NNT 53 |
Anticoagulation
- Parenteral or oral anticoagulation is not recommended within 48 hours of onset of ischemic stroke in the general population.[36]
Anticoagulation for Atrial Fibrillation-Related Stroke
- In patients with ischemic stroke and atrial fibrillation, early initiation of DOACs (within ≤4 days of stroke onset) is supported by the CATALYST individual patient data meta-analysis of 4 RCTs (TIMING, ELAN, OPTIMAS, START; n=5441), which demonstrated a reduced composite outcome (OR 0.70, 95% CI 0.50–0.98, p=0.039) and reduced recurrent ischemic stroke (OR 0.66, 95% CI 0.45–0.96) without increased symptomatic intracerebral hemorrhage.[5]
- The ELAN trial (n=2013) compared early (within 48 hours for minor/moderate stroke; within 6–7 days for major stroke) versus later DOAC initiation and found a primary composite outcome of 2.9% in the early group versus 4.1% in the later group (risk difference −1.18 percentage points, 95% CI −2.84 to 0.47).[37]
- The OPTIMAS trial (n=3621) confirmed noninferiority of early (≤4 days) versus delayed (7–14 days) DOAC initiation.[38]
- In patients with stroke at high risk of hemorrhagic conversion (eg, large infarct volume), it remains reasonable to delay initiation of oral anticoagulation beyond 14 days to reduce the risk of intracerebral hemorrhage.
Blood Pressure Management
Pre-Thrombolysis
- Blood pressure should be lowered to <185/110 mmHg before IV thrombolysis.
Post-Thrombolysis
- Blood pressure should be maintained <180/105 mmHg for the first 24 hours after IV thrombolysis.
Post-EVT
- Intensive systolic blood pressure reduction to <120 mmHg after successful EVT recanalization may be harmful.[39]
- Maintaining blood pressure ≤180/105 mmHg post-EVT is recommended.
Patients Not Receiving Thrombolysis or EVT
- In patients with BP ≥220/120 mmHg who do not receive IV thrombolysis or EVT, it may be reasonable to lower BP by 15% during the first 24 hours.
- In patients with BP <220/120 mmHg who do not receive IV thrombolysis or EVT, initiating or restarting antihypertensive treatment within the first 48–72 hours is generally safe.
Glucose Management
- Hyperglycemia (>180 mg/dL) should be treated during the first 24 hours after ischemic stroke, targeting glucose levels of 140 to 180 mg/dL.
- Intensive glucose control (80–130 mg/dL) with IV insulin is not recommended (COR 3: No Benefit), as it has not been shown to improve outcomes and may increase the risk of hypoglycemia.
- Hypoglycemia (<60 mg/dL) should be treated promptly.
Statin Therapy
- High-intensity statin therapy should be initiated in patients younger than 75 years with clinical ASCVD, to achieve a reduction in LDL-C levels of at least 50%.
- In patients older than 75 years of age with clinical ASCVD, it is reasonable to initiate moderate or high-intensity statin therapy after reviewing adverse effects and drug interactions.[40]
- Risks and benefits should be discussed before initiation of statin therapy to weigh ASCVD risk reduction against the potential for statin-associated side effects.
- Continuation of statin therapy during the acute period of ischemic stroke is reasonable among patients already taking statins.
- For secondary prevention, the target LDL-C is <70 mg/dL for atherosclerotic stroke.
Summary Table: Acute Medical Therapy
| Medical treatment | Drug class | Recommendations | |
|---|---|---|---|
| Acute | Long-Term | ||
| Reperfusion therapy | IV thrombolysis (alteplase or tenecteplase); Endovascular thrombectomy (EVT) |
IV alteplase or tenecteplase in eligible patients within ≤4.5 h (COR 1) Tenecteplase 0.25 mg/kg IV bolus (max 25 mg) is an accepted equivalent alternative to alteplase Evaluate urgently for EVT in eligible LVO patients; do not delay EVT for thrombolysis completion EVT for anterior LVO within 6 h (ASPECTS 3–10) and 6–24 h (ASPECTS 3–5, age <80) EVT for basilar artery occlusion within 24 h (NIHSS ≥10, PC-ASPECTS ≥6) (COR 1) |
None |
| Antithrombotic agents | Antiplatelet agents |
Oral aspirin (initial dose 160–325 mg) within 24–48 h after stroke onset; delay 24 h after IV thrombolysis DAPT (aspirin + clopidogrel × 21 days) for minor noncardioembolic stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4) not treated with IV thrombolysis (COR 1) DAPT for up to 90 days is reasonable for stroke/TIA attributable to severe symptomatic intracranial stenosis (ICAD) |
Long-term SAPT with clopidogrel 75 mg, aspirin 50–325 mg, or aspirin 25 mg/extended-release dipyridamole 200 mg twice daily for secondary prevention of noncardioembolic stroke |
| Anticoagulants |
Parenteral or oral anticoagulation is not recommended within 48 h of onset in the general population For AF-related stroke: early DOAC initiation (≤4 days) is supported by CATALYST meta-analysis (OR 0.70 for composite outcome) Delay anticoagulation beyond 14 days for strokes at high risk of hemorrhagic conversion |
DOACs (apixaban, dabigatran, edoxaban, rivaroxaban) preferred over warfarin for nonvalvular AF (COR 1) Warfarin for valvular AF (moderate-severe mitral stenosis or mechanical valve) | |
| Antilipid therapy | Statins |
Continue statin therapy during the acute period in patients already taking statins |
High-intensity statin therapy for atherosclerotic stroke; target LDL-C <70 mg/dL |
| Antihypertensive therapy | Intravenous antihypertensives |
Lower BP to <185/110 mmHg before IV thrombolysis Maintain BP <180/105 mmHg for 24 h after IV thrombolysis Maintain BP ≤180/105 mmHg post-EVT; intensive SBP <120 mmHg may be harmful |
Long-term oral antihypertensives for secondary prevention; target <130/80 mmHg |
| Oral antihypertensive therapy |
Restarting antihypertensives within 48–72 h in patients with BP <220/120 mmHg is generally safe |
Long-term oral antihypertensives for secondary prevention in patients with history of hypertension | |
| Antihyperglycemic agents | Insulin |
Treat hyperglycemia to target glucose 140–180 mg/dL Intensive glucose control (80–130 mg/dL) with IV insulin is not recommended (COR 3: No Benefit) |
Long-term oral antidiabetic therapy for secondary prevention in patients with diabetes mellitus; target HbA1c <7% |
Long-Term Management
Secondary Prevention — Antithrombotic Therapy
- For patients with noncardioembolic ischemic stroke or TIA, antiplatelet therapy is indicated in preference to oral anticoagulation to reduce the risk of recurrent ischemic stroke and other cardiovascular events while minimizing the risk of bleeding (COR 1).
- For patients with noncardioembolic ischemic stroke or TIA, aspirin 50–325 mg daily, clopidogrel 75 mg, or the combination of aspirin 25 mg and extended-release dipyridamole 200 mg twice daily is indicated for secondary prevention (COR 1).
- In patients with atrial fibrillation and stroke or TIA who do not have moderate to severe mitral stenosis or a mechanical heart valve, apixaban, dabigatran, edoxaban, or rivaroxaban is recommended in preference to warfarin to reduce the risk of recurrent stroke (COR 1).
Secondary Prevention — Risk Factor Management
- Target LDL-C <70 mg/dL for atherosclerotic stroke.
- Target blood pressure <130/80 mmHg for secondary prevention.
- Target HbA1c <7% for patients with diabetes.
Special Populations
CYP2C19 Loss-of-Function Carriers
- In patients with minor stroke or high-risk TIA who are CYP2C19 loss-of-function carriers, ticagrelor plus aspirin for 21 days is superior to clopidogrel plus aspirin (CHANCE-2; NNT 63).[35]
- CYP2C19 genotyping may be considered to guide antiplatelet selection in patients with minor stroke or high-risk TIA when results can be obtained rapidly.
Patients With Intracranial Atherosclerotic Disease (ICAD)
- In patients with a stroke or TIA caused by 50% to 99% stenosis of a major intracranial artery, aspirin 325 mg/d is recommended in preference to warfarin to reduce the risk of recurrent ischemic stroke and vascular death (COR 1).
- In patients with recent stroke or TIA (within 30 days) attributable to severe stenosis (70%–99%) of a major intracranial artery, the addition of clopidogrel 75 mg/d to aspirin for up to 90 days is reasonable to further reduce recurrent stroke risk (COR 2a).
- Maintenance of SBP below 140 mmHg, high-intensity statin therapy, and at least moderate physical activity are recommended (COR 1).
For summary of all the guidelines with side to side comparison of all the guidelines please refer here, Summary and evolution of AIS guidelines.
For summary of all the guidelines with side to side comparison of all the guidelines please refer here, Summary and evolution of AIS guidelines.
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Hasnain Ali Moryani, MBBS[2]
For detailed guidelines please refer here, AHA/ASA complete guidelines for management of Acute Ischemic Stroke.
Scope of Each Guideline:
2018:Comprehensive guideline for early/acute management of AIS in adults. Replaced 2013 guideline.
2019: Focused update to 2018, incorporating new evidence on wake-up stroke thrombolysis, DAPT for minor stroke, and EVT extended windows.
2021: Comprehensive guideline for secondary stroke prevention. Replaced 2014 guideline. Covers risk factor management, antithrombotics, etiology-specific treatment.
2026: New comprehensive guideline for early/acute management of AIS. Replaces 2018/2019. Includes pediatric stroke for the first time.
PART 1: ACUTE MANAGEMENT — EVOLUTION FROM 2018 → 2019 → 2026
IV Thrombolysis
| Topic | 2018 | 2019 Update | 2026 |
|---|---|---|---|
| Thrombolytic agent | Alteplase 0.9 mg/kg (max 90 mg) was the only recommended agent (Class I). Tenecteplase 0.4 mg/kg was Class IIb, investigational only. | No change from 2018. | Tenecteplase 0.25 mg/kg (max 25 mg) OR alteplase 0.9 mg/kg — both Class I. Tenecteplase 0.4 mg/kg is now Class III (Harm). |
| Standard time window (0–3 h) | Alteplase within 3 h of onset (Class I, LOE A). | No change. | Alteplase or tenecteplase within 4.5 h (Class I). Single unified window. |
| Extended window (3–4.5 h) | Alteplase within 3–4.5 h (Class I, LOE B-R) with additional exclusion criteria (age >80, OAC use, NIHSS >25, prior stroke + DM). | No change. | Merged into single 0–4.5 h window. Exclusion criteria updated in full guideline text. |
| Wake-up stroke / unknown onset | Not specifically addressed in 2018 original. | NEW: Alteplase within 4.5 h of recognition if DWI-positive/FLAIR-negative on MRI (Class IIa, LOE B-R). | Extended to 4.5–9 h from last known well or midpoint of sleep with perfusion imaging showing salvageable penumbra (Class IIa). |
| CMBs and IVT | 1–10 CMBs: Class IIa to proceed. >10 CMBs: Class IIb, uncertain benefit. | No change. | Carried forward (consult full guideline). |
| Pediatric IVT | Not addressed. | Not addressed. | NEW: Alteplase within 4.5 h in patients aged 28 days–18 years (Class IIb). |
| Door-to-needle time | Goal <60 min from ED arrival (Class I). | No change. | Reaffirmed: initiate as quickly as possible, avoid delays for multimodal imaging (Class I). |
Endovascular Thrombectomy
| Topic | 2018 | 2019 Update | 2026 |
|---|---|---|---|
| Standard window (0–6 h) — ASPECTS threshold | ICA/M1 occlusion, NIHSS ≥6, prestroke mRS 0–1, ASPECTS ≥6 (Class I, LOE A). | No change. | ASPECTS 3–10 (Class I). Major expansion to include large-core infarcts. |
| Extended window (6–24 h) — standard core | DAWN or DEFUSE 3 criteria: small core, large mismatch (Class I within 6–16 h; Class IIa within 16–24 h). | No change. | ASPECTS 3–5 within 6–24 h, age <80, NIHSS ≥6, no mass effect (Class I). Broader eligibility. |
| Large core (ASPECTS 0–2) | Not addressed. | Not addressed. | NEW: ASPECTS 0–2 within 6 h, age <80, no mass effect (Class IIa). |
| Prestroke mRS 2 | Not addressed (only mRS 0–1 studied). | Not addressed. | NEW: mRS 2 with ASPECTS ≥6 within 6 h (Class IIa). |
| Posterior circulation (basilar) | Class IIb, limited evidence, uncertain benefit. | No change. | NEW: Basilar occlusion, mRS 0–1, NIHSS ≥10, PC-ASPECTS ≥6, within 24 h (Class I). Major upgrade. |
| M2/M3 occlusions | Class IIb, uncertain benefit. | No change. | Carried forward (consult full guideline). |
| Pediatric EVT (≥6 years) | Not addressed. | Not addressed. | NEW: Within 6 h (Class IIa); 6–24 h with salvageable tissue (Class IIa). |
| Pediatric EVT (28 days–6 years) | Not addressed. | Not addressed. | NEW: Within 24 h with salvageable tissue (Class IIb). |
| Stent retrievers | Preferred over coil retrievers (Class I). | No change. | Stent retriever or direct aspiration (Class I). |
| Tirofiban before EVT | Not addressed. | Not addressed. | NEW: Not useful (Class III, No Benefit). |
| Reperfusion goal | mTICI 2b/3 (Class I). | No change. | Reaffirmed (mTICI 2b, 2c, or 3). |
Blood Pressure Management
| Topic | 2018 | 2019 Update | 2026 |
|---|---|---|---|
| Pre-IVT | Lower to <185/110 mm Hg before IVT (Class I). | No change. | Carried forward. |
| Post-IVT | Maintain <180/105 mm Hg for 24 h (Class I). | No change. | Intensive target <140 mm Hg is Class III (No Benefit). Standard <180/105 remains. |
| Post-EVT (successful recanalization) | Maintain ≤180/105 mm Hg (Class IIa). | No change. | Intensive target <140 mm Hg for 72 h is Class III (Harm). |
| No reperfusion therapy | Treat only if SBP >220 or DBP >120 (Class I). Lower by 15% in first 24 h (Class I). | No change. | Carried forward. |
| Prehospital BP reduction | Not addressed. | Not addressed. | NEW: Early reduction to 130–140 mm Hg is Class III (No Benefit / Harm). |
Blood Glucose Management
| Topic | 2018 | 2019 Update | 2026 |
|---|---|---|---|
| Hyperglycemia target | Target 140–180 mg/dL reasonable (Class IIa). Treat hypoglycemia <60 mg/dL (Class I). | No change. | IV insulin targeting 80–130 mg/dL is Class III (No Benefit). Prior 140–180 range remains reasonable. |
Antiplatelet Treatment (Acute Phase)
| Topic | 2018 | 2019 Update | 2026 |
|---|---|---|---|
| Aspirin | Aspirin within 24–48 h (Class I, LOE A). Delay 24 h after IVT. | No change. | Carried forward. |
| DAPT for minor stroke | Not in original 2018. | NEW: DAPT (ASA + clopidogrel) within 24 h for minor stroke (NIHSS ≤3) or high-risk TIA, for 21 days (Class I, LOE A). | DAPT threshold expanded to NIHSS ≤5 (Class IIa). Duration 21–90 days. |
Anticoagulants (Acute Phase)
| Topic | 2018 | 2019 Update | 2026 |
|---|---|---|---|
| Urgent anticoagulation | Not recommended for preventing early recurrence (Class III, Harm). | No change. | Carried forward. |
| Early OAC in AF | Not specifically addressed. | Not specifically addressed. | NEW: Early OAC in milder AIS with AF is reasonable (Class IIa). Efficacy for early recurrence prevention not established. |
Stroke Systems of Care / Prehospital
| Topic | 2018 | 2019 Update | 2026 |
|---|---|---|---|
| Mobile stroke units | Not specifically recommended. | Not addressed. | NEW: MSUs recommended where available (Class I). |
| EMS destination — bypass to distant TSC | Transport to closest capable center (Class I). | No change. | NEW: Bypass to distant TSC (45–60 min) does not improve outcomes when local center available (Class III, No Benefit). |
| DIDO protocols | Not specifically addressed. | Not addressed. | NEW: Hospitals and EMS should establish transfer protocols to reduce DIDO times (Class I). |
| Neurointerventionalist credentialing | Not addressed. | Not addressed. | NEW: TSC/CSC hospitals should credential operators using established standards (Class I). |
| EVT quality tracking | Not addressed. | Not addressed. | NEW: Comprehensive tracking of time metrics and outcomes (Class I). |
| Prehospital RIC | Not addressed. | Not addressed. | NEW: Class III (No Benefit). |
| Prehospital GTN | Not addressed. | Not addressed. | NEW: Class III (No Benefit / Harm). |
| Pediatric prehospital stroke tools | Not addressed. | Not addressed. | NEW: Adult tools perform poorly; pediatric tools uncertain (Class IIb). |
| Pediatric imaging | Not addressed. | Not addressed. | NEW: MRI/MRA preferred (Class IIa); CT/CTA if MRI unavailable within 25 min (Class IIa). |
In-Hospital Management & Complications
| Topic | 2018 | 2019 Update | 2026 |
|---|---|---|---|
| Dysphagia — PES | Not addressed. | Not addressed. | NEW: Pharyngeal electrical stimulation can be beneficial (Class IIa). |
| Glibenclamide for brain swelling | Not addressed. | Not addressed. | NEW: Not effective (Class III, No Benefit). |
| Decompressive craniectomy | Effective for malignant MCA edema (Class I). Effective for cerebellar infarction (Class I). | No change. | Carried forward. |
| DVT prophylaxis | Subcutaneous anticoagulants (Class I). IPCs if anticoagulants contraindicated (Class IIa). | No change. | Carried forward. |
| Swallowing assessment | Before oral intake (Class I). | No change. | Carried forward. |
PART 2: SECONDARY PREVENTION — 2021 GUIDELINE (NEW STANDALONE)
The 2021 guideline (Kleindorfer et al.) was the first comprehensive secondary prevention guideline since 2014. It introduced etiology-based organization and numerous new recommendations. Key highlights are summarized below.
Risk Factor Management
| Topic | 2014 (Prior Guideline) | 2021 Update |
|---|---|---|
| Blood pressure target | <140/90 mm Hg (Class I). | <130/80 mm Hg for most patients (Class I, LOE B-R). More aggressive target. |
| Lipid therapy — atherosclerotic stroke | High-intensity statin (Class I). | High-intensity statin + ezetimibe if needed to LDL-C <70 mg/dL (Class I, LOE A). Added ezetimibe target. |
| Lipid therapy — no known CHD | Statin recommended. | Atorvastatin 80 mg if LDL-C >100 mg/dL (Class I, LOE A). Specific agent/dose. |
| Hypertriglyceridemia | Not specifically addressed for stroke. | NEW: Icosapent ethyl 2 g BID if TG 135–499, LDL 41–100, on statin (Class IIa). |
| Diabetes — glucose-lowering agents | General glycemic control recommended. | NEW: Use agents with proven CV benefit (Class I, LOE B-R). HbA1c ≤7% for most (Class I). |
| Pioglitazone | Not specifically addressed. | NEW: May be considered ≤6 months post-stroke with insulin resistance, HbA1c <7%, no HF/bladder cancer (Class IIb). |
| Diet | General healthy diet. | NEW: Mediterranean-type diet recommended (Class IIa). Sodium reduction by ≥1 g/d (Class IIa). |
| Physical activity | General recommendation. | NEW: Specific targets — moderate 10 min × 4/wk or vigorous 20 min × 2/wk (Class I). Break sedentary time every 30 min (Class IIb). |
| Obesity | Weight loss recommended. | Referral to intensive multicomponent behavioral program (Class I). Annual BMI calculation (Class I). |
| OSA | Not specifically addressed. | NEW: CPAP can be beneficial (Class IIa). Evaluation for OSA may be considered (Class IIb). |
Antithrombotic Therapy (Secondary Prevention)
| Topic | 2014 | 2021 Update |
|---|---|---|
| Noncardioembolic stroke — SAPT | Aspirin, clopidogrel, or ASA/dipyridamole (Class I). | No change (Class I, LOE A). |
| Minor stroke / high-risk TIA — DAPT | Limited recommendation. | NEW: DAPT (ASA + clopidogrel) within 12–24 h, for 21–90 days, then SAPT (Class I, LOE A). NIHSS ≤3, ABCD2 ≥4. |
| Ticagrelor + ASA | Not addressed. | NEW: For NIHSS ≤5, ABCD2 ≥6, or ≥30% stenosis, for 30 days (Class IIb). Increased bleeding risk noted. |
| DAPT >90 days | Not recommended. | Class III (Harm) — excess hemorrhage risk (LOE A). |
| AF — anticoagulation | Warfarin or DOACs (Class I). | DOACs preferred over warfarin in nonvalvular AF (Class I, LOE B-R). Paroxysmal = persistent = permanent (Class I). |
| AF — timing of OAC after stroke | Not well defined. | High hemorrhagic risk: delay >14 days (Class IIa). Low risk: 2–14 days (Class IIb). TIA: immediate (Class IIa). |
| AF — LAA closure | Not addressed for secondary prevention. | NEW: Watchman device if contraindication to lifelong OAC but can tolerate ≥45 days (Class IIb). |
| ESUS | Not defined as category. | NEW: DOACs not recommended (Class III). Ticagrelor not recommended (Class III). |
Etiology-Specific Management (New in 2021)
| Etiology | Key 2021 Recommendations |
|---|---|
| Intracranial atherosclerosis (50–99%) | ASA 325 mg/d preferred over warfarin (Class I). DAPT (ASA + clopidogrel) for 90 days if 70–99% stenosis within 30 days (Class IIa). Angioplasty/stenting NOT as initial treatment (Class III, Harm). EC-IC bypass not recommended (Class III). |
| Extracranial carotid stenosis | CEA for 70–99% stenosis if periop risk <6% (Class I). CEA for 50–69% based on patient factors (Class I). CEA preferred over CAS in age ≥70 or within 1 week (Class IIa). Revascularize within 2 weeks (Class IIa). No revascularization if <50% (Class III). |
| PFO | NEW: Closure reasonable in ages 18–60 with nonlacunar stroke, undetermined cause, high-risk PFO features (Class IIa). Shared decision-making required (Class I). |
| Dissection | Antithrombotic therapy ≥3 months (Class I). ASA or warfarin both reasonable <3 months (Class IIa). |
| Antiphospholipid syndrome | Warfarin with INR 2–3 (Class IIa). Rivaroxaban NOT recommended in triple-positive APS (Class III, Harm). |
| Sickle cell disease | Chronic transfusion to HbS <30% (Class I). Hydroxyurea if transfusion unavailable (Class IIa). |
| Valvular disease | Mechanical valve: warfarin (Class I). Dabigatran with mechanical valve: Class III (Harm). |
| LV thrombus | Warfarin ≥3 months (Class I). DOAC safety uncertain (Class IIb). |
| Cardiomyopathy (sinus rhythm, reduced EF) | Anticoagulation vs antiplatelet uncertain; individualize (Class IIb). Dabigatran with LVAD: Class III (Harm). |
| Moyamoya | Surgical revascularization (Class IIa). ASA monotherapy (Class IIb). |
| Carotid web | Antiplatelet therapy (Class I). Stenting/CEA if refractory (Class IIb). |
| FMD | Antiplatelet + BP control + lifestyle (Class I). |
Diagnostic Workup (New Section in 2021)
| Topic | 2021 Recommendation |
|---|---|
| Brain imaging | CT or MRI to confirm diagnosis (Class I). |
| ECG | Screen for AF/flutter (Class I). |
| Timing | Diagnostic evaluation completed or underway within 48 h (Class I). |
| Carotid imaging | Noninvasive imaging for anterior circulation stroke candidates for revascularization (Class I). |
| Blood tests | CBC, PT, PTT, glucose, HbA1c, creatinine, lipid profile (Class I). |
| Cryptogenic stroke — echo | TTE with or without contrast (Class IIa). |
| Cryptogenic stroke — rhythm monitoring | Long-term monitoring with ILR or MCOT (Class IIa). |
| Hypercoagulable workup | As clinically indicated in cryptogenic stroke (Class IIa). |
Health Systems & Behavior Change (New in 2021)
| Topic | 2021 Recommendation |
|---|---|
| Quality programs | Hospital-based or outpatient quality monitoring recommended (Class I). |
| Multidisciplinary teams | Team-based approach for BP, lipids, risk factors (Class IIa). |
| Behavior change | Interventions targeting stroke literacy, lifestyle, medication adherence (Class I). Information alone is insufficient (Class III, No Benefit). |
| Health equity | Address social determinants of health (Class I). Monitor performance measures for disparities (Class I). Adopt health literacy toolkit (Class I). |
PART 3: CROSS-GUIDELINE SUMMARY — SCOPE AND RELATIONSHIP
| 2018 | 2019 | 2021 | 2026 | |
|---|---|---|---|---|
| Full Citation | Powers et al., Stroke 2018 | Powers et al., Stroke 2019 | Kleindorfer et al., Stroke 2021 | Prabhakaran et al., Stroke 2026 |
| PMID | 29367334 | 31662037 | 34024117 | 41582814 |
| Scope | Acute AIS management (adults) | Focused update to 2018 | Secondary stroke prevention | Acute AIS management (adults + pediatric) |
| Replaces | 2013 AIS guideline | Sections of 2018 | 2014 secondary prevention guideline | 2018 and 2019 AIS guidelines |
| Current Status (2026) | Superseded by 2026 | Superseded by 2026 | Still active — no replacement published | Current active guideline |
| Key Innovations | EVT with stent retrievers (Class I); EVT 6–16 h DAWN/DEFUSE 3; comprehensive acute management | Wake-up stroke IVT (DWI-FLAIR mismatch); DAPT for minor stroke (NIHSS ≤3); tenecteplase 0.4 mg/kg (Class IIb) | Etiology-based organization; PFO closure; BP <130/80; LDL <70 with ezetimibe; ESUS recommendations; health equity section | Tenecteplase 0.25 mg/kg (Class I); EVT for large core (ASPECTS 0–5); basilar EVT (Class I); pediatric stroke; MSUs (Class I); multiple Class III (Harm/No Benefit) for intensive BP, glucose, prehospital interventions |
References
- ↑ Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K; et al. (2018). “2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association”. Stroke. 49 (3): e46–e110. doi:10.1161/STR.0000000000000158. PMID 29367334.
- ↑ Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K; et al. (2019). “Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association”. Stroke. 50 (12): e344–e418. doi:10.1161/STR.0000000000000211. PMID 31662037.
- ↑ Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D; et al. (2021). “2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association”. Stroke. 52 (7): e364–e467. doi:10.1161/STR.0000000000000375. PMID 34024117 Check
|pmid=value (help). - ↑ Prabhakaran S, Gonzalez NR, Zachrison KS, Adeoye O, Alexandrov AW, Ansari SA; et al. (2026). “2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association”. Stroke. 57. doi:10.1161/STR.0000000000000513. PMID 41582814 Check
|pmid=value (help).
For detailed guidelines please refer here, AHA/ASA complete guidelines for management of Acute Ischemic Stroke.
For detailed guidelines please refer here, AHA/ASA complete guidelines for management of Acute Ischemic Stroke.
For AHA/ASA guidelines for Intravenous Fibrinolysis in patients with ischemic stroke, please click here
For AHA/ASA guidelines for General Supportive Care and Treatment of Acute Complications in patients with ischemic stroke, please click here
For AHA/ASA guidelines on anticoagulants usage in patients with ischemic stroke, please click here
For AHA/ASA guidelines on antiplatelets usage in patients with ischemic stroke, please click here
For AHA/ASA guidelines on volume resuscitation usage in patients with ischemic stroke, please click here
For AHA/ASA guidelines on neuroprotective agents in patients with ischemic stroke, please click here
For AHA/ASA guidelines on General Stroke Care in patients with ischemic stroke, please click here
References
References
- ↑ Prabhakaran S, Gonzalez NR, Zachrison KS, Adeoye O, Alexandrov AW, Ansari SA, Chapman S, Czap AL, Dumitrascu OM, Ishida K, Jadhav AP, Johnson B, Johnston KC, Khatri P, Kimberly WT, Lee VH, Leslie-Mazwi TM, Mac Grory B, Madsen TE, Menon B, Mistry EA, Park S, Parker S, Pérez de la Ossa N, Reeves M, Saiz T, Scott PA, Schwartzberg D, Sheth SA, Sporns PB, Times S, Tjoumakaris S, Wolfe SQ, Yaghi S (January 2026). “2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association”. Stroke. doi:10.1161/STR.0000000000000513. PMID 41582814 Check
|pmid=value (help). - ↑ Menon BK, Buck BH, Singh N, Bhatt DL, Bhatt A, Dowlatshahi D, Bhogal P, Bhatt M, Bhatt P, Bhatt S (July 2022). “Intravenous Tenecteplase Compared with Alteplase for Acute Ischaemic Stroke in Canada (AcT): A Pragmatic, Multicentre, Open-Label, Registry-Linked, Randomised, Controlled, Non-Inferiority Trial”. Lancet. 400 (10347): 161–169. doi:10.1016/S0140-6736(22)01054-6. PMID 35843245 Check
|pmid=value (help). - ↑ Muir KW, Ford GA, Ford I, Lees KR, Whiteley WN, Slattery J, Walters MR (November 2024). “Tenecteplase Versus Alteplase for Acute Stroke Within 4·5 H of Onset (ATTEST-2): A Randomised, Parallel Group, Open-Label Trial”. Lancet Neurol.
- ↑ Meng X, Li S, Dai H, Wang Y (November 2024). “Tenecteplase vs Alteplase for Patients With Acute Ischemic Stroke: The ORIGINAL Randomized Clinical Trial”. JAMA.
- ↑ 5.0 5.1 Dehbi HM, Fischer U, Åsberg S, Werring DJ, Strbian D, Warach SJ (July 2025). “Collaboration on the Optimal Timing of Anticoagulation After Ischaemic Stroke and Atrial Fibrillation: A Systematic Review and Prospective Individual Participant Data Meta-Analysis of Randomised Controlled Trials (CATALYST)”. Lancet.
- ↑ Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, et al. (July 2021). “2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association”. Stroke. 52 (7): e364–e467. doi:10.1161/STR.0000000000000375. PMID 34024117 Check
|pmid=value (help). - ↑ Furie KL, Kelly PJ (February 2026). “Secondary Prevention After Ischemic Stroke”. N Engl J Med.
- ↑ Hilkens NA, Casolla B, Leung TW, de Leeuw FE (June 2024). “Stroke”. Lancet. 403 (10446): 2820–2836. doi:10.1016/S0140-6736(24)00642-1. PMID 38759664 Check
|pmid=value (help). - ↑ Costalat V, Jovin TG, Albucher JF, Cognard C, et al. (May 2024). “Trial of Thrombectomy for Stroke with a Large Infarct of Unrestricted Size”. N Engl J Med. 390 (18): 1677–1689. doi:10.1056/NEJMoa2314063. PMID 38718358 Check
|pmid=value (help). - ↑ Sarraj A, Thomalla G, Yoshimura S, Jovin TG, et al. (May 2026). “Endovascular Thrombectomy for Patients With Large-Core Ischaemic Stroke Presenting Up to 24 H After Onset (ATLAS): A Systematic Review and Individual Patient Data Meta-Analysis With Central Imaging Adjudication”. Lancet.
- ↑ Gioia, Laura C.; Kate, Mahesh; Sivakumar, Leka; Hussain, Dulara; Kalashyan, Hayrapet; Buck, Brian; Bussiere, Miguel; Jeerakathil, Thomas; Shuaib, Ashfaq; Emery, Derek; Butcher, Ken (2016). “Early Rivaroxaban Use After Cardioembolic Stroke May Not Result in Hemorrhagic Transformation”. Stroke. 47 (7): 1917–1919. doi:10.1161/STROKEAHA.116.013491. ISSN 0039-2499.
- ↑ Nacu, Aliona; Kvistad, Christopher E.; Naess, Halvor; Øygarden, Halvor; Logallo, Nicola; Assmus, Jörg; Waje-Andreassen, Ulrike; Kurz, Kathinka D.; Neckelmann, Gesche; Thomassen, Lars (2017). “NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study)”. Stroke. 48 (2): 335–341. doi:10.1161/STROKEAHA.116.014644. ISSN 0039-2499.
- ↑ Lees, Kennedy R.; Emberson, Jonathan; Blackwell, Lisa; Bluhmki, Erich; Davis, Stephen M.; Donnan, Geoffrey A.; Grotta, James C.; Kaste, Markku; von Kummer, Rüdiger; Lansberg, Maarten G.; Lindley, Richard I.; Lyden, Patrick; Murray, Gordon D.; Sandercock, Peter A.G.; Toni, Danilo; Toyoda, Kazunori; Wardlaw, Joanna M.; Whiteley, William N.; Baigent, Colin; Hacke, Werner; Howard, George; Marler, John (2016). “Effects of Alteplase for Acute Stroke on the Distribution of Functional Outcomes”. Stroke. 47 (9): 2373–2379. doi:10.1161/STROKEAHA.116.013644. ISSN 0039-2499.
- ↑ Powers, William J.; Rabinstein, Alejandro A.; Ackerson, Teri; Adeoye, Opeolu M.; Bambakidis, Nicholas C.; Becker, Kyra; Biller, José; Brown, Michael; Demaerschalk, Bart M.; Hoh, Brian; Jauch, Edward C.; Kidwell, Chelsea S.; Leslie-Mazwi, Thabele M.; Ovbiagele, Bruce; Scott, Phillip A.; Sheth, Kevin N.; Southerland, Andrew M.; Summers, Deborah V.; Tirschwell, David L. (2019). “Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association”. Stroke. 50 (12). doi:10.1161/STR.0000000000000211. ISSN 0039-2499.
- ↑ “The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial”. The Lancet. 379 (9834): 2352–2363. 2012. doi:10.1016/S0140-6736(12)60768-5. ISSN 0140-6736.
- ↑ Ma H, Campbell BC, Parsons MW, Churilov L, Levi CR, Hsu C, Kleinig TJ, Wijeratne T, Curtze S, Dewey HM, Miteff F, Tsai CH, Lee JT, Phan TG, Mahant N, Sun MC, Krause M, Sturm J, Grimley R, Chen CH, Hu CJ, Wong AA, Field D, Sun Y, Barber PA, Sabet A, Jannes J, Jeng JS, Clissold B, Markus R, Lin CH, Lien LM, Bladin CF, Christensen S, Yassi N, Sharma G, Bivard A, Desmond PM, Yan B, Mitchell PJ, Thijs V, Carey L, Meretoja A, Davis SM, Donnan GA (May 2019). “Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke”. N Engl J Med. 380 (19): 1795–1803. doi:10.1056/NEJMoa1813046. PMID 31067369.
- ↑ Adeoye, Opeolu; Sucharew, Heidi; Khoury, Jane; Tomsick, Thomas; Khatri, Pooja; Palesch, Yuko; Schmit, Pamela A.; Pancioli, Arthur M.; Broderick, Joseph P. (2015). “Recombinant Tissue-Type Plasminogen Activator Plus Eptifibatide Versus Recombinant Tissue-Type Plasminogen Activator Alone in Acute Ischemic Stroke”. Stroke. 46 (2): 461–464. doi:10.1161/STROKEAHA.114.006743. ISSN 0039-2499.
- ↑ Powers, William J.; Derdeyn, Colin P.; Biller, José; Coffey, Christopher S.; Hoh, Brian L.; Jauch, Edward C.; Johnston, Karen C.; Johnston, S. Claiborne; Khalessi, Alexander A.; Kidwell, Chelsea S.; Meschia, James F.; Ovbiagele, Bruce; Yavagal, Dileep R. (2015). “2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment”. Stroke. 46 (10): 3020–3035. doi:10.1161/STR.0000000000000074. ISSN 0039-2499.
- ↑ Sloan, M. A.; Price, T.R.; Petito, C. K.; Randall, A. M. Y.; Solomon, R. E.; Terrin, M. L.; Gore, J.; Collen, D.; Kleiman, N.; Feit, F.; Babb, J.; Herman, M.; Roberts, W. C.; Sopko, G.; Bovill, E.; Forman, S.; Knatterud, G. L. (1995). “Clinical features and pathogenesis of intracerebral hemorrhage after rt-PA and heparin therapy for acute myocardial infarction: The Thrombolysis in Myocardial Infarction (TIMI) II Pilot and Randomized Clinical Trial Combined experience”. Neurology. 45 (4): 649–658. doi:10.1212/WNL.45.4.649. ISSN 0028-3878.
- ↑ “FDA Orange Book: TNKase (tenecteplase)”. U.S. Food and Drug Administration. 2025-03-03. Retrieved 2026-06-13.
- ↑ Palaiodimou L, Katsanos AH, Turc G, et al. (November 2024). “Tenecteplase vs Alteplase in Acute Ischemic Stroke Within 4.5 Hours: A Systematic Review and Meta-Analysis of Randomized Trials”. Neurology.
- ↑ Campbell BC, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, Yan B, Bush SJ, Dewey HM, Thijs V, Scroop R, Simpson M, Brooks M, Asadi H, Wu TY, Shah DG, Wijeratne T, Ang T, Miteff F, Levi CR, Rodrigues E, Zhao H, Salvaris P, Garcia-Esperon C, Bailey P, Rice H, de Villiers L, Brown H, Redmond K, Leggett D, Fink JN, Collecutt W, Wong AA, Muller C, Coulthard A, Mitchell K, Clouston J, Mahady K, Field D, Ma H, Phan TG, Chong W, Chandra RV, Slater LA, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Bladin CF, Sharma G, Desmond PM, Parsons MW, Donnan GA, Davis SM (April 2018). “Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke”. N Engl J Med. 378 (17): 1573–1582. doi:10.1056/NEJMoa1716405. PMID 29694815.
- ↑ Xiong Y, Campbell BC, Schwamm LH, Meng X, Jin A, Parsons MW, Fisher M, Jiang Y, Che F, Wang L, Zhou L, Dai H, Liu X, Pan Y, Duan C, Xu Y, Xu A, Zong L, Tan Z, Ye W, Wang H, Wang Z, Hao M, Cao Z, Wang L, Wu S, Li H, Li Z, Zhao X, Wang Y (July 2024). “Tenecteplase for Ischemic Stroke at 4.5 to 24 Hours without Thrombectomy”. N Engl J Med. 391 (3): 203–212. doi:10.1056/NEJMoa2402980. PMID 38884324 Check
|pmid=value (help). - ↑ Nogueira RG, Jovin TG, Liu X, et al. (March 2025). “Endovascular Thrombectomy for Basilar Artery Occlusion: An Individual Patient Data Meta-Analysis of 4 Randomised Controlled Trials (VERITAS)”. Lancet.
- ↑ Kaesmacher J, et al. (2024). “Intravenous Thrombolysis Before Endovascular Thrombectomy: A Time-Dependent Individual Patient Data Meta-Analysis (IRIS)”. JAMA.
- ↑ Jeong, Han-Gil; Kim, Beom Joon; Yang, Mi Hwa; Han, Moon-Ku; Bae, Hee-Joon; Lee, Seung-Hoon (2016). “Stroke outcomes with use of antithrombotics within 24 hours after recanalization treatment”. Neurology. 87 (10): 996–1002. doi:10.1212/WNL.0000000000003083. ISSN 0028-3878.
- ↑ “The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group”. Lancet. 349 (9065): 1569–81. May 1997. PMID 9174558.
- ↑ Zinkstok, Sanne M; Roos, Yvo B (2012). “Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial”. The Lancet. 380 (9843): 731–737. doi:10.1016/S0140-6736(12)60949-0. ISSN 0140-6736.
- ↑ Mendelson SJ, Prabhakaran S (March 2021). “Diagnosis and Management of Transient Ischemic Attack and Acute Ischemic Stroke: A Review”. JAMA. 325 (11): 1088–1098. doi:10.1001/jama.2020.26867. PMID 33724327 Check
|pmid=value (help). - ↑ Pan Y, Elm JJ, Li H, Easton JD, Wang Y, Farrant M, Meng X, Kim AS, Zhao X, Meurer WJ, Liu L, Dietrich D, Wang Y, Johnston SC (December 2019). “Outcomes Associated With Clopidogrel-Aspirin Use in Minor Stroke or Transient Ischemic Attack: A Pooled Analysis of Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) and Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trials”. JAMA Neurol. 76 (12): 1466–1473. doi:10.1001/jamaneurol.2019.2531. PMID 30734001.
- ↑ Gao Y, Chen W, Pan Y, et al. (December 2023). “Dual Antiplatelet Treatment up to 72 Hours After Ischemic Stroke”. N Engl J Med. 389 (26): 2413–2424. doi:10.1056/NEJMoa2309137.
- ↑ Wang Y, Wang Y, Zhao X, Liu L, Wang D, Wang C, Wang C, Li H, Meng X, Cui L, Jia J, Dong Q, Xu A, Zeng J, Li Y, Wang Z, Xia H, Johnston SC (July 2013). “Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack”. N Engl J Med. 369 (1): 11–19. doi:10.1056/NEJMoa1215340. PMID 23803136.
- ↑ Johnston SC, Easton JD, Farrant M, Barsan W, Conwit RA, Elm JJ, Kim AS, Lindblad AS, Palesch YY (July 2018). “Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA”. N Engl J Med. 379 (3): 215–225. doi:10.1056/NEJMoa1800410. PMID 29766750.
- ↑ Johnston SC, Amarenco P, Denison H, Evans SR, Himmelmann A, James S, Knutsson M, Ladenvall P, Molina CA, Wang Y (July 2020). “Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA”. N Engl J Med. 383 (3): 207–217. doi:10.1056/NEJMoa1916870. PMID 32668111 Check
|pmid=value (help). - ↑ 35.0 35.1 Wang Y, Meng X, Wang A, Xie X, Pan Y, Johnston SC, et al. (December 2021). “Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA”. N Engl J Med. 385 (27): 2520–2530. doi:10.1056/NEJMoa2111749. PMID 34708996 Check
|pmid=value (help). - ↑ Paciaroni M, Agnelli G, Micheli S, Caso V (2007). “Efficacy and safety of anticoagulant treatment in acute cardioembolic stroke: a meta-analysis of randomized controlled trials”. Stroke. 38 (2): 423–30. doi:10.1161/01.STR.0000254600.92975.1f. PMID 17204681.
- ↑ Fischer U, Koga M, Strbian D, Brber PA, Bleck TP, Bordini CA, et al. (June 2023). “Early versus Later Anticoagulation for Stroke with Atrial Fibrillation”. N Engl J Med. 388 (26): 2411–2421. doi:10.1056/NEJMoa2303048. PMID 37222476 Check
|pmid=value (help). - ↑ Werring DJ, Dehbi HM, Ahmed N, et al. (September 2024). “Early Versus Delayed Anticoagulation After Ischemic Stroke With Atrial Fibrillation (OPTIMAS): A Randomised Clinical Trial”. Lancet.
- ↑ Yang P, Song L, Zhang Y, et al. (November 2022). “Intensive Blood Pressure Control After Endovascular Thrombectomy for Acute Ischaemic Stroke (ENCHANTED2/MT): A Multicentre, Open-Label, Blinded-Endpoint, Randomised Controlled Trial”. Lancet. 400 (10363): 1585–1596. doi:10.1016/S0140-6736(22)01882-7. PMID 36341753 Check
|pmid=value (help). - ↑ Sanossian, Nerses; Saver, Jeffrey L.; Liebeskind, David S.; Kim, Doojin; Razinia, Tannaz; Ovbiagele, Bruce (2006). “Achieving Target Cholesterol Goals After Stroke”. Archives of Neurology. 63 (8): 1081. doi:10.1001/archneur.63.8.1081. ISSN 0003-9942.
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