What are the treatment options for ischemic stroke (cerebrovascular accident)?

From the Guidelines

Intravenous thrombolysis with recombinant tissue plasminogen activator (r-tPA) is the primary treatment for ischemic stroke and should be administered within 4.5 hours of symptom onset. The treatment options for ischemic stroke (cerebrovascular accident) focus on restoring blood flow to the brain as quickly as possible.

Treatment Options

• Intravenous thrombolysis with r-tPA at a dose of 0.9 mg/kg (maximum 90 mg), with 10% given as a bolus and the remainder infused over 60 minutes, is the mainstay of early treatment of acute ischemic stroke, as stated in the 2015 American Heart Association/American Stroke Association guidelines 1.
• For eligible patients with large vessel occlusions presenting within 24 hours of symptom onset, mechanical thrombectomy is recommended to physically remove the clot.
• After the acute phase, antiplatelet therapy is initiated, typically with aspirin 325 mg initially, followed by 81 mg daily, or clopidogrel 75 mg daily, as recommended by the American College of Chest Physicians evidence-based clinical practice guidelines 1.
• For secondary prevention, high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) is recommended regardless of baseline cholesterol levels.
• Blood pressure management targets <140/90 mmHg with medications like ACE inhibitors or ARBs.
• Patients with atrial fibrillation require anticoagulation, typically with direct oral anticoagulants like apixaban 5 mg twice daily or warfarin with a target INR of 2-3.

Key Considerations

• Time is critical in stroke treatment, as each minute of delay results in the loss of approximately 1.9 million neurons.
• Every effort should be made to shorten any delays in the initiation of treatment because earlier treatments are associated with increased benefits, as emphasized in the 2015 American Heart Association/American Stroke Association guidelines 1.
• The American College of Chest Physicians evidence-based clinical practice guidelines recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A) and suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention 1.

From the FDA Drug Label

The CURE study included 12,562 patients with ACS without ST-elevation (UA or NSTEMI) and presenting within 24 hours of onset of the most recent episode of chest pain or symptoms consistent with ischemia Patients were randomized to receive clopidogrel (300 mg loading dose followed by 75 mg once daily) or placebo, and were treated for up to one year Patients also received aspirin (75 to 325 mg once daily) and other standard therapies such as heparin. The number of patients experiencing the primary outcome (CV death, MI, or stroke) was 582 (9.3%) in the clopidogrel-treated group and 719 (11.4%) in the placebo-treated group, a 20% relative risk reduction (95% CI of 10% to 28%; p <0. 001) for the clopidogrel-treated group Table 4: Outcome Events in the CURE Primary Analysis Outcome Clopidogrel (+ aspirin)* (n=6259) Placebo (+ aspirin)* (n=6303) Relative Risk Reduction (%) (95% CI) Primary outcome (Cardiovascular death, MI, stroke) 582 (9.3%) 719 (11.4%) 20% (10.3,27.9) All Individual Outcome Events: CV death 318 (5.1%) 345 (5.5%) 7% (-7.7,20.6) MI 324 (5.2%) 419 (6.6%) 23% (11,33.4) Stroke 75 (1.2%) 87 (1.4%) 14% (-17.7,36. 6)

The treatment options for ischemic stroke (cerebrovascular accident) include:

• Antiplatelet therapy: Clopidogrel, in combination with aspirin, has been shown to reduce the relative risk of stroke by 14% in patients with acute coronary syndrome.
• Aspirin: Used in combination with clopidogrel, aspirin is a standard therapy for patients with ischemic stroke.
• Other standard therapies: Such as heparin, may be used in combination with clopidogrel and aspirin to treat ischemic stroke. 2

From the Research

Treatment Options for Ischemic Stroke

The treatment options for ischemic stroke include:

• Thrombolysis using intravenous tissue plasminogen activator (tPA) 3, 4, 5, 6
• Endovascular (intraarterial) treatment, although its efficacy is not supported by clinical trials 4
• Low-dose tPA with urokinase (UK) as an alternative to standard tPA administration 5
• Nanothrombolysis using tPA-based nanocarriers, which is a promising strategy to improve the efficacy and safety of tPA therapy 7

Thrombolysis using tPA

Thrombolysis using intravenous tPA is the only available evidence-based treatment for acute ischemic stroke 3. The use of tPA has been shown to decrease disability at 90 days from stroke onset 3. However, its utilization is limited by a narrow therapeutic window and selective efficacy 7.

Eligibility for tPA Treatment

The eligibility for tPA treatment is limited by several factors, including:

• Time from stroke onset, with a window of 3-4.5 hours 3, 6
• Neurologic criteria, such as mild neurologic impairment and rapidly improving symptoms 6
• Presence of contraindications, such as increased hemorrhage risk 4

Future Directions

Future research is needed to:

• Characterize the physicochemical characteristics and in vivo behavior of tPA-loaded nanocarriers 7
• Explore the combination of tPA-based nanothrombolysis and neuroprotection as a promising treatment strategy for acute ischemic stroke 7
• Develop theranostic nanocarriers co-delivered with tPA and imaging agents for future stroke management 7