Should IV Alteplase Be Given at 7 Hours with Perfusion Mismatch?
Direct Answer
No, intravenous alteplase should NOT be administered to this patient presenting at 7 hours, even with favorable perfusion imaging, because the 2026 AHA guidelines assign a Class 2a recommendation (not Class 1) for extended-window thrombolysis based on perfusion studies—reflecting that the evidence remains insufficient to support routine IV alteplase beyond 4.5 hours when relying solely on CT perfusion mismatch. Instead, mechanical thrombectomy is the definitive revascularization strategy for this patient with a documented large vessel occlusion (distal A2 segment) presenting in the 6–24 hour window with favorable perfusion imaging. 1
Why Class 2a and Not Class 1?
The Evidence Gap for CT Perfusion-Based Selection Beyond 4.5 Hours
The 2026 AHA guidelines provide Class 2a (moderate) recommendation—not Class 1 (strong)—for IV alteplase after 4.5 hours based on perfusion imaging because the pivotal trials (WAKE-UP, EXTEND) used MRI DWI-FLAIR mismatch, not CT perfusion mismatch, as selection criteria. 1
CT perfusion-based selection for IV alteplase in the extended window (4.5–9 hours) remains unproven according to contemporary stroke guidelines; the Canadian Stroke Best Practice Recommendations explicitly state that this approach lacks validation. 1
MRI DWI-FLAIR mismatch has Level A evidence supporting alteplase administration up to 4.5 hours from symptom recognition in wake-up or unknown-onset strokes, but your patient is at 7 hours with CT perfusion—a different imaging modality with weaker supporting data for thrombolysis alone. 1
Why the Downgrade Matters Clinically
Class 2a means "reasonable to perform" but acknowledges conflicting evidence or divergence of opinion about usefulness/efficacy; it does NOT carry the same weight as Class 1 ("should be performed"), which reflects high-certainty benefit. 1
The 2026 guidelines reserve strong (Class 1) recommendations for mechanical thrombectomy in the 6–24 hour window when perfusion imaging demonstrates salvageable tissue—precisely your patient's scenario. 1
The Correct Treatment Algorithm for This Patient
Step 1: Confirm Large Vessel Occlusion and Perfusion Mismatch
Obtain CT angiography to document the distal A2 segment occlusion (already done in your case). 1
Confirm perfusion imaging criteria: ischemic core ≤70 mL, penumbra ≥10 mL, mismatch ratio ≥1.8 (your patient has core ~20 mL and ratio 8, meeting all thresholds). 1
Verify ASPECTS ≥6 on non-contrast CT to exclude extensive irreversible injury (required for thrombectomy eligibility in the 6–24 hour window). 1
Step 2: Proceed Directly to Mechanical Thrombectomy
Patients with large vessel occlusion presenting 6–24 hours after last known well who have favorable perfusion imaging (small core, large penumbra) should receive mechanical thrombectomy with a stent retriever or direct aspiration—this is a Class 1, Level A recommendation. 1
The technical goal is modified Thrombolysis in Cerebral Infarction (mTICI) grade 2b/3 reperfusion; do not delay thrombectomy to observe for clinical response or to administer IV alteplase first. 1
Mechanical thrombectomy is recommended for patients ≥18 years, pre-stroke mRS 0–1, causative ICA or MCA-M1 occlusion, NIHSS ≥6, ASPECTS ≥6, and groin puncture achievable within 6 hours (or 6–24 hours with perfusion mismatch)—your patient meets all criteria except the vessel is distal A2, which may require individualized neurointerventional assessment. 1
Step 3: Do NOT Administer IV Alteplase in This Scenario
IV alteplase is absolutely contraindicated when symptom onset exceeds 4.5 hours unless MRI demonstrates DWI-FLAIR mismatch (not CT perfusion mismatch); your patient is at 7 hours with CT perfusion only. 1, 2
Even if alteplase were considered under a Class 2a recommendation, it should never delay mechanical thrombectomy; any delay to endovascular therapy is associated with worse outcomes. 1
The 2007 Stroke journal review noted that treatment "may still be beneficial beyond 3 hours up until 4.5 hours," but explicitly did not extend this window further without additional trial data—data that remains incomplete for CT perfusion-guided thrombolysis at 7 hours. 3
Common Pitfalls and How to Avoid Them
Pitfall 1: Conflating MRI-Based and CT-Based Extended-Window Protocols
Do not assume that favorable CT perfusion mismatch is equivalent to MRI DWI-FLAIR mismatch for alteplase eligibility; the evidence base is distinct, and guidelines reflect this difference. 1
MRI DWI-FLAIR mismatch identifies tissue that is ischemic but not yet infarcted (FLAIR-negative), providing a biological "tissue clock" that CT perfusion does not replicate with the same validation. 1
Pitfall 2: Delaying Thrombectomy to Administer Alteplase
Never observe a patient after IV alteplase to assess clinical response before proceeding to thrombectomy; this practice is explicitly discouraged because every minute of delay worsens functional outcomes. 1
In patients with confirmed large vessel occlusion, thrombectomy should be initiated immediately, even if alteplase is being considered—though in this case at 7 hours with CT perfusion, alteplase is not indicated. 1
Pitfall 3: Misinterpreting Class 2a as "Probably Should Do"
Class 2a reflects moderate-strength evidence with some uncertainty; it does NOT mean "routinely recommended" but rather "may be reasonable in selected cases after careful consideration." 1
When a Class 1 alternative exists (mechanical thrombectomy), it should be prioritized over a Class 2a intervention (extended-window alteplase with CT perfusion). 1
Why Distal A2 Occlusion May Influence the Decision
Thrombectomy Feasibility in Distal Vessels
The 2026 AHA guidelines specify that mechanical thrombectomy has the strongest evidence for ICA or MCA-M1 occlusions; distal A2 segment occlusions are smaller vessels where thrombectomy feasibility depends on institutional expertise and device navigability. 1
If thrombectomy is deemed technically unfeasible by the neurointerventional team, the patient still does NOT qualify for IV alteplase at 7 hours with CT perfusion alone—this remains outside guideline-supported practice. 1, 2
What to Do If Thrombectomy Is Not Possible
Consult a stroke specialist to determine whether the patient might qualify for enrollment in a clinical trial evaluating extended-window thrombolysis with advanced imaging, as recommended when considering alteplase after 4.5 hours. 1
Provide best medical management, including antiplatelet therapy, statin initiation, blood pressure control, and monitoring for neurologic deterioration—but do not administer alteplase outside validated time windows and imaging criteria. 1, 2
Summary of the 2026 Guideline Position
The 2026 AHA guidelines assign Class 2a (not Class 1) to extended-window IV alteplase because the evidence base relies on MRI DWI-FLAIR mismatch, not CT perfusion mismatch, and because mechanical thrombectomy has superseded thrombolysis as the primary reperfusion strategy in the 6–24 hour window for large vessel occlusions. 1
Your patient at 7 hours with CT perfusion mismatch and a distal A2 occlusion should be evaluated urgently for mechanical thrombectomy; if thrombectomy is feasible, proceed immediately without alteplase. 1
If thrombectomy is not feasible, alteplase remains contraindicated at 7 hours with CT perfusion alone, and the patient should receive optimal medical management. 1, 2