A 58-year-old man with hypertension and diabetes presents with acute onset right-sided weakness and speech difficulty. CT head shows no hemorrhage. Regarding thrombolytic therapy in acute ischemic stroke, all of the following are established indications or benefits EXCEPT:

Explanation

## Thrombolytic Therapy in Acute Ischemic Stroke: Indications & Contraindications ### Key Point: **IV alteplase (rt-PA) does NOT reduce mortality in acute ischemic stroke; it reduces disability and improves functional outcomes.** This is a critical distinction — the benefit of thrombolysis is in reducing long-term disability (mRS shift), not in reducing death rates. ### High-Yield Facts on IV Alteplase (rt-PA): | Aspect | Detail | |--------|--------| | **Time window** | ≤4.5 hours from symptom onset (FDA-approved: 3 hrs; extended window: 3–4.5 hrs per ECASS III) | | **Dose** | 0.9 mg/kg (max 90 mg); 10% bolus, remainder over 1 hour | | **Mortality effect** | **No significant reduction in mortality** — benefit is functional outcome improvement | | **Disability reduction** | Significant improvement in mRS 0–1 at 3 months (NINDS trial, Cochrane meta-analysis) | | **Bleeding risk** | Symptomatic ICH ~6% (vs ~1% placebo) — may offset mortality benefit | | **Warfarin contraindication** | INR > 1.7 is an absolute contraindication | | **Minor symptoms** | Relative contraindication — risk-benefit unfavorable for NIHSS ≤5 | ### Clinical Pearl: The **NINDS rt-PA Stroke Study (1995)** demonstrated that alteplase improved functional outcomes at 3 months (30% more patients had minimal or no disability), but **did NOT show a statistically significant reduction in mortality**. The Cochrane systematic review of thrombolytics in acute ischemic stroke similarly confirms improved functional independence without a clear mortality benefit. In fact, early deaths from thrombolysis-related ICH may offset any survival advantage. ### Why Each Option Is Correct (Except the Answer): - **Option A (correct statement):** INR > 1.7 on warfarin is a well-established absolute contraindication to IV alteplase due to markedly increased ICH risk — per AHA/ASA guidelines. - **Option C (correct statement):** Minor or rapidly improving symptoms are a **relative contraindication**, not an indication. Thrombolysis is generally reserved for patients with significant neurological deficit (NIHSS ≥6). Hence, stating it is "indicated" in minor symptoms is false — but this is a true statement about a contraindication, making it a correct fact. - **Option D (correct statement):** Administration within 4.5 hours improves functional outcomes — confirmed by NINDS, ECASS III, and ATLANTIS trials. - **Option B (INCORRECT/EXCEPTION):** The claim that "thrombolysis reduces **mortality**" is **not established**. The evidence supports reduction in disability and improved functional outcomes, not mortality reduction. This is the EXCEPT answer. ### Mnemonic for Contraindications to IV rt-PA: **BRAIN BLEED** — (B)leeding history, (R)ecent surgery, (A)ctive malignancy, (I)NR >1.7, (N)ew stroke <3 months, (B)P >185/110, (L)ow platelets (<100K), (E)vidence of ICH, (E)xtended time >4.5 hrs, (D)iabetic retinopathy. [cite: Harrison 21e Ch 379; NINDS rt-PA Stroke Study Group, NEJM 1995; Cochrane Review: Thrombolysis for acute ischaemic stroke]