Intravenous thrombolysis (IVT) remains the cornerstone of acute ischemic stroke treatment, with established efficacy across diverse patient populations and evolving evidence supporting novel thrombolytic agents. This evidence-based guide provides clinicians with the latest recommendations, agent selection criteria, and management strategies to optimize patient outcomes.
Key Update (June 2025): FDA approval of tenecteplase for acute ischemic stroke and new data from the RAISE trial showing reteplase superiority over alteplase. OPTIMISTmain trial demonstrates safety of reduced monitoring intensity in stable patients [3][4][5].
Time Windows and Eligibility Criteria
The therapeutic benefit of IV thrombolysis is highly time-dependent, with earlier treatment yielding substantially better outcomes:
| Time Window | Evidence Level | Key Criteria | Number Needed to Treat (NNT) |
|---|---|---|---|
| 0-3 hours | Level A | Disabling deficits, no contraindications | 8-10 for mRS 0-1 [2][5] |
| 3-4.5 hours | Level A | Additional exclusions: Age ≤80, no oral anticoagulants, NIHSS ≤25, no prior stroke + diabetes [2] | 12-19 for mRS 0-1 [2][5] |
| 4.5-9 hours (imaging-selected) | Level B-R | CTP/MRI mismatch: Core <70mL, mismatch ratio>1.2, mismatch volume >10mL [5][7] | 14 for mRS 0-1 [5] |
| Wake-up stroke (WUS) | Level B-R | DWI/FLAIR mismatch on MRI [5] | ~8 for mRS 0-1 [5] |
Clinical Imperative: Every 10-minute delay in treatment reduces disability-free life by 40 days. Target door-to-needle time ≤30 minutes with ≥90% of patients treated within 60 minutes of arrival [2][7].
Thrombolytic Agents: Evidence and Selection
Alteplase: The Standard Agent
- Dosing: 0.9 mg/kg (max 90mg), 10% bolus + 90% infusion over 60 minutes [5][7]
- Landmark Trials: NINDS (1995) established 0-3h benefit; ECASS 3 extended to 4.5h [2]
- Efficacy: 39% vs 26% mRS 0-1 at 3 months in 0-3h window [2]
- Safety: Symptomatic ICH rate 2.4-5.2% in clinical trials [2]
Tenecteplase: The New Standard
- Dosing: 0.25 mg/kg (max 25mg) single bolus over 5-10 seconds [5][7]
- FDA Approval: 2025 for acute ischemic stroke [3]
- Advantages: Bolus administration, higher fibrin specificity, longer half-life [3]
- Superior in LVO: EXTEND-IA TNK showed 22% complete reperfusion vs 10% with alteplase pre-thrombectomy [5]
- Safety Note: 0.4 mg/kg dose associated with worse outcomes (NOR-TEST 2) [5]
Reteplase: Emerging Evidence
- RAISE Trial (2024): Superior functional outcomes vs alteplase (79.5% vs 70.4% mRS 0-1) but higher hemorrhage risk [3]
- Dosing: Double-bolus regimen (10 + 10IU or 0.9mg/kg equivalent)
- Time-Dependent Benefit: Potential greater efficacy in early time windows but increased major hemorrhage in late window (181-270 min) [3]
- Current Status: Not yet approved for stroke; requires further validation in diverse populations [3]
| Agent | Dose | Administration | Advantages | Considerations |
|---|---|---|---|---|