## Drug of Choice for Acute Ischemic Stroke **Key Point:** Alteplase (rt-PA) is the gold-standard thrombolytic agent for acute ischemic stroke within 4.5 hours of symptom onset, approved by FDA and recommended by all major guidelines (AHA/ASA, ESC). ### Mechanism & Rationale Alteplase is a fibrin-specific plasminogen activator that: - Preferentially binds to fibrin in the thrombus - Minimizes systemic fibrinolysis and bleeding risk - Achieves rapid recanalization of cerebral vessels - Has the strongest evidence base in acute stroke (NINDS rt-PA Study, ECASS III) ### Comparison of Thrombolytics in Stroke | Agent | Fibrin Specificity | Route | Dosing in Stroke | Clinical Use in Stroke | | --- | --- | --- | --- | --- | | **Alteplase** | High | IV | 0.9 mg/kg (max 90 mg) | **Gold standard** | | Streptokinase | Low | IV | Not used in stroke | Contraindicated (high ICH risk) | | Urokinase | Intermediate | IV/IA | Rarely used | Inferior to alteplase | | Tenecteplase | High | IV bolus | Investigational in stroke | Not yet standard of care | **High-Yield:** Alteplase is the ONLY thrombolytic with proven benefit in acute ischemic stroke and is class I recommendation in all major guidelines. ### Exclusion Criteria to Remember Do NOT give alteplase if: - Hemorrhage on imaging (ruled out here) - Symptom onset > 4.5 hours - Recent surgery or head trauma - Severe thrombocytopenia (< 100,000/μL) - INR > 1.7 (if on warfarin) **Clinical Pearl:** Even though tenecteplase has a longer half-life and can be given as a single bolus, it remains investigational in stroke and is not yet approved for routine use in most countries. **Warning:** Streptokinase is absolutely contraindicated in acute stroke due to high risk of intracranial hemorrhage and poor recanalization rates.
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