For an adult with acute ischemic stroke presenting within 4.5 hours, should I use alteplase (recombinant tissue‑type plasminogen activator) or tenecteplase as the first‑line intravenous thrombolytic?

Alteplase vs Tenecteplase for Acute Ischemic Stroke

Alteplase remains the standard first-line intravenous thrombolytic for acute ischemic stroke within 4.5 hours, though tenecteplase (0.25 mg/kg) is emerging as a reasonable alternative with similar efficacy and safety. 1

Current Guideline-Based Recommendations

Alteplase: The Established Standard

Alteplase is the only FDA-approved thrombolytic with Class I, Level A evidence for acute ischemic stroke treatment within 3 hours of symptom onset. 1

• Within 0-3 hours: Alteplase (0.9 mg/kg, maximum 90 mg) should be offered to all eligible patients meeting NINDS criteria, with 10% given as IV bolus over 1 minute and 90% infused over 60 minutes 1, 2

• Within 3-4.5 hours: Alteplase should be considered for patients meeting ECASS III criteria (excluding those >80 years, NIHSS >25, on oral anticoagulants, or with both diabetes and prior stroke) 1

• Blood pressure must be <185/110 mmHg before treatment and maintained <180/105 mmHg for 24 hours post-administration 1, 2

Tenecteplase: The Emerging Alternative

The American Heart Association/American Stroke Association currently gives tenecteplase a Class IIb recommendation (Level B-R), meaning it "might be considered" as an alternative to alteplase in patients with minor neurological impairment and no major intracranial occlusion. 3

• Dosing is simpler: 0.25 mg/kg (maximum 25 mg) as a single IV bolus over 5-10 seconds, eliminating the need for 60-minute infusion 3

• The 2024 ORIGINAL trial (n=1,465) demonstrated noninferiority: 72.7% of tenecteplase patients achieved mRS 0-1 at 90 days versus 70.3% with alteplase (RR 1.03,95% CI 0.97-1.09) 4

• Safety profiles are equivalent: Symptomatic intracranial hemorrhage occurred in 1.2% of both groups, with 90-day mortality of 4.6% (tenecteplase) vs 5.8% (alteplase) 4

Key Clinical Decision Points

When to Strongly Consider Alteplase

• Any patient within 3 hours of symptom onset where you have established stroke protocols and experience 1
• Institutions without specific tenecteplase protocols or experience 1
• When regulatory/medicolegal considerations favor FDA-approved agents 1

When Tenecteplase May Be Preferred

• Logistical advantages are critical: Single bolus administration reduces nursing time, eliminates infusion pump requirements, and simplifies pre-hospital or mobile stroke unit administration 3, 5
• Large vessel occlusion with planned thrombectomy: Tenecteplase shows potentially superior early recanalization rates, though definitive evidence from ongoing trials (BRIDGE-TNK) is pending 5, 6
• Cost considerations: Tenecteplase is cost-effective, saving €21 per patient while gaining 0.05 QALYs compared to alteplase 7

Critical Contraindications (Apply to Both Agents)

Both agents share identical absolute contraindications that must be verified before administration: 1, 3

• Prior intracranial hemorrhage (any time)
• Ischemic stroke or severe head trauma within 3 months
• Intracranial/spinal surgery within 3 months
• Active internal bleeding or GI malignancy with bleeding within 21 days
• Blood pressure >185/110 mmHg unresponsive to treatment
• Platelet count <100,000/mm³ or INR >1.7
• Blood glucose <50 mg/dL

Common Pitfalls to Avoid

Time is brain—do not delay treatment while debating agent choice. The benefit of thrombolysis decreases by approximately 1.9 million brain cells per minute of delay 1

• Protocol violations increase symptomatic ICH risk: Institutions treating <5 patients/year have significantly worse outcomes 1
• The 3-4.5 hour window requires stricter exclusions: Patients >80 years, NIHSS >25, on any oral anticoagulant, or with both diabetes and prior stroke are excluded 1
• Do not withhold treatment for "mild" symptoms if disabling: A patient with isolated aphasia or hand weakness may have devastating functional impact 1

Practical Algorithm for Agent Selection

If your institution has an established alteplase protocol with good outcomes, continue using alteplase. 1

If transitioning to tenecteplase or starting a new protocol, tenecteplase offers equivalent outcomes with practical advantages, particularly for:

• Pre-hospital administration 3, 5
• Patients proceeding to thrombectomy 5, 6
• Resource-limited settings where infusion monitoring is challenging 3, 7

The most important factor is not which agent you choose, but rather treating eligible patients as rapidly as possible within established protocols with experienced teams. 1