What are the current guideline‑recommended acute interventions (including tissue plasminogen activator and endovascular thrombectomy) and secondary prevention strategies for an adult presenting with acute ischemic stroke?

Acute Ischemic Stroke Management

Intravenous alteplase 0.9 mg/kg (maximum 90 mg) within 3 hours of symptom onset is the single most critical intervention for acute ischemic stroke, and endovascular thrombectomy should be added for large vessel occlusions within 6 hours when specific criteria are met. 1

Hyperacute Phase: Time-Critical Interventions

Intravenous Thrombolysis with Alteplase

Administer IV alteplase 0.9 mg/kg (maximum 90 mg)—10% as bolus over 1 minute, remaining 90% over 60 minutes—for patients presenting within 3 hours of last known well. 2, 1 This is the only FDA-approved therapy for acute ischemic stroke and results in 37% of patients recovering to fully independent function when guidelines are followed. 1

• For patients presenting between 3 and 4.5 hours, alteplase may be considered but with weaker evidence of benefit. 2
• Beyond 4.5 hours, do not administer IV alteplase. 2
• Target door-to-needle time: median 30 minutes, with 90th percentile at 60 minutes. 2 Every 15-minute reduction in door-to-needle time decreases in-hospital mortality by 5%. 1, 3

Blood Pressure Management for Thrombolysis

Before initiating alteplase, reduce blood pressure to <185/110 mmHg. 2, 1 This is an absolute requirement—do not give alteplase if this target cannot be achieved. 1

• During and for 24 hours after alteplase infusion, maintain blood pressure ≤180/105 mmHg. 2, 1
• Use labetalol or nicardipine for rapid BP control in this setting. 1

Endovascular Thrombectomy

Perform mechanical thrombectomy with stent retrievers (Solitaire, Trevo) for patients meeting all criteria: prestroke mRS 0-1, large vessel occlusion (internal carotid or proximal M1) confirmed on CTA, age ≥18 years, NIHSS ≥6, ASPECTS ≥6, and groin puncture possible within 6 hours of symptom onset. 2, 1, 4

• The 2015 Canadian guidelines introduced endovascular therapy as a major advancement based on five randomized trials (MR CLEAN, ESCAPE, SWIFT PRIME, EXTEND-IA, REVASCAT) showing improved outcomes. 2
• Select patients may be treated within 12 hours if they meet specific imaging and clinical criteria. 2
• Endovascular therapy should not delay IV alteplase in eligible patients—both can be administered. 2, 1

Diagnostic Imaging Protocol

Obtain non-contrast head CT within 25 minutes of arrival to exclude hemorrhage and identify early ischemic changes. 1, 3 CT interpretation must occur within 45 minutes for thrombolytic candidates. 1, 3

• Add CT angiography for all patients presenting within treatment windows to identify large vessel occlusion. 2, 1
• CT perfusion may be added in selected cases but should never delay thrombolysis. 2, 1
• Do not postpone IV thrombolysis to obtain advanced multimodal imaging—rapid treatment supersedes additional imaging. 1

Blood Pressure Management (Non-Thrombolysis Patients)

Practice permissive hypertension in acute ischemic stroke unless systolic/diastolic pressure exceeds 220/120 mmHg—aggressive lowering jeopardizes penumbral perfusion. 1

• If blood pressure is <220/120 mmHg, do not initiate antihypertensive therapy within the first 48-72 hours, as it does not reduce death or dependency and may worsen outcomes. 1
• When pressure reaches ≥220/120 mmHg, consider a modest reduction of approximately 15% during the first 24 hours, though benefit is uncertain. 1

Antiplatelet Therapy

Start aspirin 325 mg within 24-48 hours after stroke onset, but wait 24 hours after alteplase and obtain repeat head CT to exclude hemorrhage before starting aspirin. 2, 1

• Aspirin's primary benefit is reduction of early recurrent stroke rather than mitigation of initial neurological injury. 1
• Never give aspirin within 24 hours of alteplase—this increases hemorrhage risk. 2, 1
• Aspirin is not a substitute for IV alteplase in patients who meet thrombolysis criteria. 1
• Do not use clopidogrel alone or in combination with aspirin for acute ischemic stroke. 1
• Do not use IV glycoprotein IIb/IIIa inhibitors outside clinical trials. 1

Anticoagulation in the Acute Phase

Do not use full-dose unfractionated heparin or low-molecular-weight heparin for acute ischemic stroke—they do not improve outcomes and increase hemorrhage risk. 2, 1

• Emergency anticoagulation does not lower the risk of early recurrent stroke, even with cardioembolic sources. 1
• Anticoagulation does not prevent early neurological worsening. 1
• Most randomized trials have failed to demonstrate benefit of acute-phase anticoagulation on functional outcomes. 1

Intra-Arterial Thrombolysis

Consider intra-arterial thrombolysis for patients with major middle-cerebral-artery occlusion presenting <6 hours after symptom onset who are ineligible for IV alteplase, but only at experienced stroke centers with immediate angiography capability. 2, 1

• This approach is reasonable for patients with contraindications to IV alteplase, such as recent surgery. 1
• Availability of intra-arterial therapy should not preclude the use of IV alteplase in eligible patients. 1

Hospital Admission and Monitoring

Admit to a dedicated stroke unit with monitored beds for at least 24 hours—stroke unit care reduces mortality and morbidity comparably to the effects of alteplase itself. 1, 3

• Maintain peripheral oxygen saturation ≥92% using pulse oximetry; provide supplemental oxygen only when saturation falls below 94%. 1
• Check core temperature every 4 hours for the first 48 hours and treat fever promptly (target ≤37.5°C)—fever reduction decreases neurological damage. 1
• Monitor neurological status frequently using NIHSS to detect early deterioration. 3

Early Mobilization and VTE Prophylaxis

Initiate early mobilization (sitting, standing, brief ambulation) within 24 hours of admission if no contraindications exist—early activity reduces complications and improves functional outcomes. 1

• Start intermittent pneumatic compression devices within 24 hours for VTE prophylaxis in immobile patients. 2, 1, 3
• If using pharmacologic prophylaxis, prophylactic-dose LMWH is preferred over prophylactic-dose UFH. 2

Secondary Prevention Strategies

Long-Term Antiplatelet Therapy

For secondary prevention after the acute phase, use aspirin 75-100 mg daily, clopidogrel 75 mg daily, aspirin/extended-release dipyridamole 25 mg/200 mg twice daily, or cilostazol 100 mg twice daily over no antiplatelet therapy. 2

• Clopidogrel or aspirin/extended-release dipyridamole are preferred over aspirin alone for secondary prevention. 2
• Do not use the combination of clopidogrel plus aspirin for long-term secondary prevention. 2

Anticoagulation for Atrial Fibrillation

In patients with a history of stroke or TIA and atrial fibrillation, use oral anticoagulation over no antithrombotic therapy, aspirin, or combination therapy with aspirin and clopidogrel. 2

Prehospital and Systems of Care

Emergency medical services should transport patients directly to the nearest Primary Stroke Center or Comprehensive Stroke Center, bypassing hospitals that lack stroke-treatment resources. 1, 3

• Stroke patients must be triaged with the same priority as acute myocardial infarction or serious trauma, regardless of neurological deficit severity. 1, 3
• Paramedics should provide prehospital notification to the ED team with detailed patient-specific information to ensure stroke teams are available upon arrival. 2

Critical Pitfalls to Avoid

Never aggressively lower blood pressure in acute stroke unless giving thrombolytics or BP >220/120 mmHg—permissive hypertension maintains penumbral perfusion and aggressive lowering worsens outcomes. 1

• Do not delay alteplase for "minor" symptoms—early treatment is critical even for seemingly mild deficits, as every 30-minute delay reduces probability of favorable outcome by 10.6%. 1
• Do not give aspirin as adjunctive therapy with alteplase—wait 24 hours and obtain repeat CT first. 1
• Do not use full-dose heparin or LMWH for acute stroke treatment—it increases hemorrhage risk without improving outcomes. 2, 1
• Assess swallowing before any oral intake to prevent aspiration. 1