What are the guidelines for intravenous alteplase thrombolysis in patients over 65 years presenting with acute ischemic stroke?

Thrombolysis Guidelines for Patients Over 65 Years with Acute Ischemic Stroke

Age over 65 years is not a contraindication to intravenous alteplase for acute ischemic stroke, and patients in this age group should receive standard-dose thrombolysis (0.9 mg/kg, maximum 90 mg) when presenting within 4.5 hours of symptom onset and meeting eligibility criteria. 1, 2

Age-Specific Treatment Windows and Eligibility

0–3 Hour Window

• All patients over 65 years, including those over 80 years, should receive IV alteplase if they meet standard eligibility criteria—age alone is not a contraindication in this early window. 1, 2
• Severe stroke (NIHSS >25) does not exclude patients over 65 from treatment within 3 hours. 1
• Current use of single or dual antiplatelet therapy does not contraindicate alteplase in patients over 65 within the 0–3 hour window. 1

3–4.5 Hour Extended Window

• Patients over 80 years are specifically excluded from alteplase treatment in the 3–4.5 hour window according to ECASS III criteria. 1, 2
• For patients aged 65–80 years in the extended window, alteplase may be administered if they do not have: oral anticoagulant use (regardless of INR), NIHSS >25, or combined history of diabetes and prior stroke. 1, 3
• Recent evidence from 2018 Canadian guidelines suggests that for patients >80 years presenting in the 3–4.5 hour window, IV alteplase can be as effective and safe as in younger patients, though this represents evolving practice beyond traditional ECASS III criteria. 3

Safety Profile in Elderly Patients

Hemorrhage Risk

• The risk of symptomatic intracerebral hemorrhage is not increased in patients aged 80 years or older compared to younger patients. 4
• Symptomatic ICH rates with alteplase range from 2.4% to 6.4% across all age groups. 1
• A baseline NIHSS score >20 is a stronger predictor of symptomatic hemorrhage than age alone. 1
• Advanced age was historically identified as a risk factor for hemorrhagic complications, but contemporary evidence does not support withholding treatment based on age. 1, 5

Efficacy in Elderly Populations

• Alteplase can be used safely and effectively in patients over 80 years with acute ischemic stroke. 5
• Evidence of increasing intracerebral hemorrhage rates among elderly patients following alteplase treatment has not been demonstrated. 5
• Severe intracranial hemorrhage is not associated with age in acute ischemic stroke patients receiving alteplase. 5

Standard Dosing and Administration Protocol

• Administer 0.9 mg/kg (maximum 90 mg total) with 10% given as IV bolus over 1 minute, followed by 90% infused over 60 minutes. 1, 2
• Treatment should be initiated as rapidly as possible, with target door-to-needle time <60 minutes in 90% of patients and median time of 30 minutes. 2, 3
• Every 15-minute delay reduces the probability of favorable functional outcome. 1

Pre-Treatment Requirements for All Ages

• Perform immediate non-contrast CT to exclude intracranial hemorrhage—this is the only mandatory imaging before alteplase. 1, 3
• Check bedside capillary glucose (must be >50 mg/dL or >3.3 mmol/L)—this is the only laboratory test that must precede alteplase administration. 1, 2
• Lower blood pressure to <185/110 mmHg before initiating alteplase and maintain <180/105 mmHg for 24 hours post-treatment. 1, 2
• Do not delay treatment to obtain complete laboratory panels beyond glucose. 1, 3

Absolute Contraindications (All Ages)

• Intracranial hemorrhage on baseline imaging. 1, 2
• Stroke or serious head trauma within preceding 3 months. 1
• Major surgery within past 14 days. 2
• Gastrointestinal or urinary bleeding within past 21 days. 2
• INR >1.7, aPTT >40 seconds, or platelets <100,000/mm³. 4
• Blood glucose <2.7 mmol/L (50 mg/dL) or >22.2 mmol/L. 4
• Current use of direct oral anticoagulants (DOACs) without specialized reversal capabilities. 2, 3

Integration with Mechanical Thrombectomy

• Do not delay IV alteplase while assessing for mechanical thrombectomy eligibility—administer alteplase even when thrombectomy is planned. 1, 3
• Do not wait to assess response to IV thrombolysis before proceeding to catheter angiography for thrombectomy. 1, 3
• For suspected large vessel occlusion, obtain CTA from aortic arch to vertex immediately after non-contrast CT, but do not delay alteplase administration. 1

Extended Window Considerations (4.5–24 Hours)

• For patients over 65 presenting 4.5–24 hours after onset with salvageable tissue on perfusion imaging, recent 2025 evidence from the HOPE trial demonstrates that alteplase improves functional independence (40% vs 26% with standard treatment), though symptomatic ICH increases (3.8% vs 0.51%). 6
• For wake-up stroke or unknown onset >4.5 hours, alteplase can be beneficial if MRI shows DWI-FLAIR mismatch. 3, 7

Common Pitfalls to Avoid

• Do not withhold alteplase from patients >80 years presenting within the 0–3 hour window—age is only an exclusion criterion in the 3–4.5 hour window. 1, 2
• Do not delay treatment waiting for complete laboratory results beyond bedside glucose. 1, 3
• Do not exclude patients with severe stroke (NIHSS >25) from treatment within 3 hours. 1
• Do not postpone IV thrombolysis to obtain or interpret vascular imaging for thrombectomy evaluation. 1, 3
• Do not confuse the alteplase stroke protocol (0.9 mg/kg) with the myocardial infarction protocol. 2