Why is mechanical thrombectomy contraindicated five days after onset of an acute large‑vessel occlusion, given that the ischemic core is established, the penumbra is lost, and the risk of hemorrhagic transformation is high?

Why Mechanical Thrombectomy is Contraindicated at Day 5 After Large-Vessel Occlusion

Mechanical thrombectomy performed 5 days (120 hours) after stroke onset is not supported by any guideline or trial evidence and should not be performed, because the ischemic core is fully established, the penumbra has been lost, there is no salvageable tissue remaining, and the risk of hemorrhagic transformation without any potential benefit makes the procedure futile and dangerous. 1, 2

Evidence-Based Time Windows for Thrombectomy

Anterior Circulation Occlusions

• 0-6 hours: Mechanical thrombectomy is Class I, Level A indicated for patients with NIHSS ≥6, ASPECTS ≥6, and confirmed large-vessel occlusion. 3

• 6-24 hours: Thrombectomy is Class I, Level A indicated only when advanced perfusion imaging (CT perfusion or MRI) demonstrates salvageable tissue meeting DAWN or DEFUSE-3 criteria (ischemic core <70 mL, mismatch ratio ≥1.8, mismatch volume ≥15 mL). 2, 3, 4

• Beyond 24 hours: Current guidelines provide no recommendation for routine thrombectomy in anterior circulation strokes beyond 24 hours. 2

Posterior Circulation (Basilar Artery) Occlusions

• 0-12 hours: Class I, Level B-R recommendation for patients with NIHSS ≥6 and PC-ASPECTS ≥6. 1

• 12-24 hours: Class IIa, Level B-R (reasonable) for the same criteria. 1

• Beyond 24 hours: Class IIb, Level C-EO (may be reasonable only case-by-case) with tremendous uncertainty regarding benefit. 1

• Critical finding: Even for basilar artery occlusions treated beyond 24 hours, isolated case reports describe attempts at 48-72 hours, but no reports support treatment at 5 days, and functional outcomes in these late cases are uniformly poor. 2

Why the Penumbra is Lost by Day 5

Temporal Evolution of Ischemic Tissue

• The ischemic penumbra—the zone of hypoperfused but viable tissue surrounding the infarct core—survives only when collateral blood flow maintains minimal perfusion above the threshold for irreversible injury. 4

• By 24 hours, most penumbral tissue has either been salvaged by spontaneous recanalization/collaterals or has progressed to irreversible infarction and joined the ischemic core. 2

• By day 5 (120 hours), the entire territory supplied by the occluded vessel has completed the transition from penumbra to established core; there is no salvageable tissue remaining. 2, 3

• Each 30-minute delay in achieving recanalization reduces the probability of good functional outcome by 8-14%, demonstrating that time-dependent tissue loss occurs rapidly in the acute phase and is essentially complete well before 5 days. 2

Why Hemorrhagic Transformation Risk is Prohibitive

Mechanism of Hemorrhagic Transformation

• Established ischemic core undergoes blood-brain barrier breakdown, endothelial damage, and loss of vascular autoregulation. 3

• Late reperfusion of infarcted tissue causes hemorrhagic transformation because damaged vessels cannot withstand restored perfusion pressure. 2, 5

Evidence on Hemorrhagic Risk

• Patients with large ischemic cores (low ASPECTS scores) experience substantially increased risk of reperfusion hemorrhage; pooled trial data show symptomatic intracranial hemorrhage rates of approximately 4-6% even in appropriately selected patients. 3

• In the context of an established core at day 5, the hemorrhagic risk is theoretically maximal because the entire territory lacks salvageable tissue and is maximally vulnerable to transformation. 3

• Pursuing thrombectomy in patients with no salvageable tissue based on a "nothing to lose" rationale is explicitly discouraged, as procedural complications can exacerbate an already catastrophic situation without any proven benefit. 3

Why ASPECTS 0 Represents the Extreme End of This Spectrum

• ASPECTS 0 indicates complete large-core stroke with extremely poor prognosis and high hemorrhagic risk. 3

• All landmark thrombectomy trials providing Level A evidence excluded patients with very low ASPECTS scores; even recent large-core trials (ANGEL-ASPECT, SELECT2, TENSION) set lower enrollment limits at ASPECTS 2-3 and did not include ASPECTS 0 patients. 3

• Endovascular thrombectomy is generally not recommended for ASPECTS 0 because it represents complete infarction with no salvageable tissue. 3

• By day 5, even patients who initially had favorable ASPECTS scores will have progressed to ASPECTS 0 or near-0 in the affected territory. 2, 3

Real-World Data Beyond 24 Hours

Outcomes in Extended Time Windows

• A multicenter registry study (STAR) comparing thrombectomy beyond 24 hours versus 6-24 hours found that patients treated beyond 24 hours were significantly less likely to achieve functional independence (18.8% vs 34.9%, P=0.005) and had higher 90-day mortality (OR 2.34, P=0.023). 5

• While the study concluded thrombectomy beyond 24 hours "appears safe," the dramatically worse outcomes reflect treatment of patients with minimal remaining penumbra. 5

• Critically, this study examined patients treated at 24-48 hours, not 5 days; extrapolating to 120 hours would predict even worse outcomes approaching zero benefit. 5

Common Pitfalls to Avoid

• Do not delay imaging or transfer in the acute phase hoping for spontaneous improvement; each 30-minute delay worsens outcomes. 2

• Do not pursue thrombectomy based solely on vessel occlusion without confirming salvageable tissue on perfusion imaging in extended time windows. 2, 3

• Do not misinterpret isolated case reports of thrombectomy at 48-72 hours as evidence supporting treatment at 5 days; these cases are exceptional and outcomes are poor. 2, 6

• Do not exclude wake-up strokes from consideration if they present within 24 hours of last-known-well and have favorable perfusion imaging. 3

Algorithmic Approach to Late-Presenting Patients

For patients presenting >24 hours after last-known-well:

1. Confirm time of onset and ensure it is truly beyond 24 hours (not a wake-up stroke within the window). 2

2. Obtain CT angiography to document vessel occlusion. 2

3. Obtain perfusion imaging (CT perfusion or MRI with diffusion/perfusion) to assess core size and penumbra. 2, 3

4. If anterior circulation:

   • No salvageable tissue (large core, no mismatch) → Do not perform thrombectomy. 2, 3
   • Salvageable tissue present → Consider thrombectomy only if within 24 hours; beyond 24 hours has no guideline support. 2

5. If basilar artery occlusion:

   • NIHSS ≥6, PC-ASPECTS ≥6 → May consider thrombectomy on highly selective case-by-case basis (Class IIb) with full informed consent about uncertain benefit. 1
   • Poor imaging or low NIHSS → Do not perform thrombectomy. 1

6. At 5 days (120 hours):

   • Do not perform thrombectomy regardless of vessel or imaging findings; no evidence supports benefit and risk is prohibitive. 2