Second-Line Treatment When Alteplase is Unavailable
Mechanical thrombectomy (endovascular therapy) is the definitive second-choice treatment for acute ischemic stroke when alteplase is unavailable, particularly for patients with large vessel occlusion. 1, 2
Primary Alternative: Mechanical Thrombectomy
Endovascular thrombectomy should be performed as the primary revascularization strategy when alteplase cannot be administered, as it is highly effective independent of thrombolytic therapy. 1, 2
Eligibility Criteria for Thrombectomy (0-6 hours):
- Age ≥18 years 2
- Pre-stroke modified Rankin Scale (mRS) score of 0-1 2
- Large vessel occlusion of the internal carotid artery or middle cerebral artery (M1 segment) 2
- NIHSS score ≥6 2
- ASPECTS ≥6 2
- Groin puncture can be initiated within 6 hours of symptom onset 2
Extended Window Thrombectomy (6-24 hours):
Mechanical thrombectomy remains effective in the 6-24 hour window when advanced imaging demonstrates salvageable brain tissue. 2 This requires:
- CT perfusion or MRI diffusion-weighted imaging showing mismatch between ischemic core and hypoperfused tissue 2
- Ischemic core ≤70 mL with penumbra ≥10 mL and mismatch ratio ≥20% 2
Technical Approach:
The goal is complete reperfusion (modified TICI grade 2b/3) using stent-retrievers with or without aspiration. 1, 2 Combined approaches using both stent-retrievers and aspiration achieve the fastest first-pass complete reperfusion. 1
Alternative Thrombolytic: Tenecteplase
Tenecteplase (0.25 mg/kg as single IV bolus) may be considered as an alternative thrombolytic agent, though it has not been proven superior to alteplase. 2, 3
Evidence for Tenecteplase:
- The ATTEST-2 trial (2024) demonstrated non-inferiority of tenecteplase 0.25 mg/kg compared to alteplase 0.9 mg/kg within 4.5 hours of symptom onset 3
- Tenecteplase offers practical advantages including single bolus administration versus 60-minute infusion 3, 4
- May have superior efficacy in large vessel occlusion cases 4, 5
- Safety profile appears equivalent to alteplase with similar rates of symptomatic intracranial hemorrhage (2% vs 2%) 3
Current Guideline Status:
Tenecteplase is not yet recommended as first-line therapy in most guidelines, but may be considered when alteplase is unavailable or in patients with minor neurological impairment without major intracranial occlusion. 2
Critical Decision Algorithm
Step 1: Determine if Large Vessel Occlusion Present
- Obtain CT angiography from arch-to-vertex immediately 1, 2
- If LVO confirmed → proceed directly to mechanical thrombectomy 1, 2
Step 2: If No Alteplase Available
- For LVO patients: Mechanical thrombectomy alone is highly effective and should not be delayed 1, 2
- For non-LVO patients: Consider tenecteplase if available and patient meets standard thrombolysis criteria 2, 3
Step 3: Time-Dependent Considerations
- Within 6 hours: Thrombectomy eligibility based on standard clinical and imaging criteria 2
- 6-24 hours: Require advanced perfusion imaging to demonstrate salvageable tissue 2
Important Caveats and Pitfalls
Do not delay mechanical thrombectomy while searching for alteplase or waiting to assess clinical response. Every 30-minute delay in recanalization decreases the chance of good functional outcome by 8-14%. 1
Thrombectomy is effective even without prior thrombolysis. The benefit of mechanical thrombectomy is independent of whether alteplase was administered. 1, 2
For patients on anticoagulation with elevated INR (>1.7), alteplase is contraindicated but mechanical thrombectomy remains the preferred revascularization strategy and should proceed without waiting for complete anticoagulation reversal. 6
Posterior circulation strokes (basilar artery occlusion) can be treated with either intravenous thrombolysis or endovascular approaches, with comparable outcomes reported for both strategies. 1
Transfer protocols must be optimized. Primary stroke centers without thrombectomy capability should have pre-planned rapid transfer arrangements to comprehensive stroke centers. 1 Use validated triage tools like ASPECTS to identify patients requiring transfer. 1