Stroke: Ischemic & Hemorrhagic—Prevention, Acute Management, and Prevention Strategies

Stroke: Ischemic vs Hemorrhagic; Prevention, Acute Management, and Secondary Prevention

  • Purpose and framing

    • This module covers arterial clots and stroke management within antithrombotic pharmacotherapy (anticoagulants and antiplatelets).
    • Optional Canvas stroke videos exist for slower, detailed review; the in-class plan is a faster pass with a focus on applying a stroke decision tree to cases.
    • Five current stroke guidelines address different aspects: primary prevention, acute ischemic stroke management, secondary prevention after stroke/TIA, and hemorrhagic stroke (intracerebral and subarachnoid). The most recent primary prevention guideline was released end of last year.

  • Key takeaways you must be able to perform

    • Differentiate ischemic vs hemorrhagic stroke; identify underlying pathophysiology for each type.
    • Distinguish modifiable vs non-modifiable risk factors; apply risk-factor modification for primary and secondary prevention.
    • Apply patient eligibility criteria to thrombolytics (tPA/tenecteplase) and select appropriate anticoagulants/antiplatelets in stroke treatment.
    • Describe appropriate therapy for different stroke etiologies (atherosclerotic vs cardioembolic) and recognize overlapping roles of antiplatelets and anticoagulants.
    • Recognize the importance of rapid assessment and time-to-treatment (time = brain).
    • Understand the role of imaging, neurology assessment (NIHSS), and monitoring in acute stroke care.

  • Stroke is multi-etiology; there are two broad categories

    • Ischemic stroke: reduced blood flow leading to tissue injury; most common type (~87%).
    • Hemorrhagic stroke: leakage of blood into brain tissue or CNS spaces; includes spontaneous intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH).
    • Distinguishing between ischemic and hemorrhagic stroke is vital because treatments are often mutually exclusive or harmful if misapplied.

  • Stroke pathophysiology concepts

    • Ischemic mechanism: thrombosis due to atherosclerosis or embolism from the heart (cardioembolic).
    • Clot lodging in cerebral vasculature → localized ischemia → tissue infarction if blood flow is not restored.
    • Ischemic core vs penumbra
    • Ischemic core: tissue with severely reduced blood flow leading to irreversible damage.
    • Penumbra: surrounding tissue with reduced flow but potentially salvageable if perfusion is restored promptly.
    • Time is critical: salvaging the penumbra preserves neurologic function; delays lead to larger infarcts.
    • Time-to-treatment concept: ext{time}
      ightarrow ext{tissue salvage}; earlier reperfusion yields greater tissue rescue.
    • TIAs are warning signs of future stroke; treated like strokes for prevention purposes.

  • Risk factors for stroke

    • Non-modifiable risk factors (orange box in lecture): age, race, family history, genetics.
    • Modifiable risk factors (first four are cardiovascular risk factors): hypertension, cigarette smoking, diabetes, dyslipidemia.
    • Other modifiable factors: existing cardiovascular disease, lifestyle factors, hormone therapies, sleep disorders, obesity, poor diet, physical inactivity, hormonal contraception, migraines, inflammation, hypercoagulable states.
    • Important note: cardiovascular risk factors affect brain, heart, and peripheral arteries similarly due to shared pathophysiology (arterial disease is not organ-specific).

  • Etiology of ischemic strokes (typical slide content)

    • Atherosclerotic-based origins: intracranial atherosclerosis, penetrating artery disease, carotid plaque/stenosis.
    • Cardioembolic origins (heart-derived clots): atrial fibrillation is the #1 cardioembolic source; other causes include valvular disease, left ventricular thrombus, post-MI clots.
    • Pathophysiology: thrombosis from atherosclerosis or emboli from the heart travel to cerebral arteries and cause occlusion, leading to ischemia and infarct.
    • Practical implication: antiplatelets are preferred for atherosclerotic (non-cardioembolic) strokes; anticoagulants are preferred for cardioembolic strokes (e.g., AFib).

  • Atrial fibrillation (AFib) in stroke prevention

    • AFib increases stroke risk via blood stasis in the atria (left atrial appendage) and cardioembolic risk.
    • Valvular AFib: associated with moderate-severe mitral stenosis or mechanical heart valves; anticoagulation with warfarin is generally required.
    • Non-valvular AFib: absence of moderate/severe mitral stenosis and mechanical valves; DOACs (DOACs = dabigatran, rivaroxaban, apixaban, edoxaban) preferred over warfarin for most patients, but warfarin remains an option depending on circumstances.
    • DOACs are not indicated for valvular AFib (mechanical valves or significant rheumatic mitral stenosis).
    • Reversal agents: idarucizumab (Praxbind) for dabigatran; andexanet alfa (Andexxa) for factor Xa inhibitors; PCC/FFP/vitamin K used for warfarin reversal; some DOAC regimens interact with P-glycoprotein inhibitors/inducers.
    • Dose considerations and interactions: each DOAC has specific dosing, renal adjustments, and drug interactions; dabigatran is dialyzable and sensitive to moisture; rivaroxaban/apixaban/edoxaban have varying interactions and monitoring considerations.
    • In risk assessment, use CHA2DS2-VASc to estimate stroke risk in AFib (see below). DOACs are typically first-line in non-valvular AFib; warfarin is reserved for valvular AFib or certain clinical scenarios.

  • CHA2DS2-VASc scoring (risk assessment for AFib-related stroke)

    • Purpose: quantify stroke risk in patients with AFib to guide anticoagulation decisions.
    • Scoring components (exact points):
    • C: congestive heart failure — 1 point
    • H: hypertension — 1 point
    • A: age ≥75 — 2 points
    • D: diabetes — 1 point
    • S: prior stroke/TIA/thromboembolism — 2 points
    • V: vascular disease (e.g., prior MI, PAD, aortic plaque) — 1 point
    • A: age 65–74 — 1 point
    • Sc: sex category (female) — 1 point
    • Maximum possible score: 9 points.
    • Practical interpretation (as taught in the lecture):
    • Low risk: score = 0 (ignore female point when interpreting risk level).
    • Moderate risk: score = 1 (anticoagulation can be considered; DOACs preferred to warfarin).
    • High risk: score ≥ 2 (anticoagulation strongly recommended; DOACs preferred).
    • Important clarifications (from the lecture):
    • The female sex point should be counted in the raw CHADS VASc score, but when interpreting risk category for treatment decisions, the female point is ignored for purposes of classifying as low/moderate/high risk.
    • The D in CHADS VASc stands for diabetes (not dyslipidemia).
    • Practical examples discussed in lecture:
    • Hypertension and diabetes with a female patient yields CHADS VASc = 3 (if female counts, otherwise 2 for risk categorization).
    • For a 70-year-old female with hypertension and diabetes, CHADS VASc = 3 (counting female); risk category may be interpreted as high-risk if the non-female factors sum to ≥2.
    • Treatment implications based on CHADS VASc:
    • Low risk (0): no anticoagulation required for primary prevention; monitor and reassess if score changes.
    • Moderate risk (1): oral anticoagulants considered; DOACs preferred over warfarin.
    • High risk (2+): oral anticoagulants indicated; DOACs preferred over warfarin.
    • Important practical notes:
    • Do not use CHADS VASc to manage VTE or ACS risk; it is specific to AFib stroke risk.
    • Warfarin remains the option for valvular AFib; DOACs are preferred for non-valvular AFib in most guidelines.

  • Anticoagulants and duration choices in AFib

    • Non-valvular AFib: DOACs preferred for stroke prevention; warfarin is an option based on patient factors.
    • Valvular AFib: warfarin is the primary choice (DOACs not indicated with mechanical valves or significant rheumatic mitral stenosis).
    • DOAC options include: dabigatran, rivaroxaban, apixaban, edoxaban. All can be used for primary prevention in non-valvular AFib with appropriate risk, and also for secondary prevention after AFib-related stroke.
    • Reversal strategies after DOACs: Praxbind for dabigatran; Andexxa for factor Xa inhibitors; PCC/FFP and vitamin K for warfarin reversal; some DOACs interact with P-gp modulators.
    • When choosing among DOACs/warfarin, consider: patient tolerability, drug interactions, need for INR monitoring, cost/formulary, and patient preference.
    • Important note: for AFib-related stroke prevention, the presence of prior stroke/TIA automatically places a patient into high risk, guiding anticoagulation decisions.

  • Acute ischemic stroke: presentation, evaluation, and management workflow

    • Clinical presentation varies with brain region affected (hemiparesis, aphasia, vertigo, dysarthria, etc.).
    • Public health note: B.S.T. mnemonic to recognize stroke signs and act fast:
    • Balance difficulty → B
    • Eyes changes → E
    • Face asymmetry → F
    • Arm weakness → A
    • Speech difficulties → S
    • Time to call 911 → T
    • Initial assessment and workup in ED:
    • History: onset time, risk factors, comorbidities, current medications.
    • Physical and neurologic exam; NIH Stroke Scale (NIHSS) to quantify deficit.
      • NIHSS ranges: 0 = no symptoms; 5–15 = moderate stroke; 16–42 = severe stroke.
    • Imaging: CT or MRI to distinguish ischemic from hemorrhagic stroke before treatment; check for tumor or mass effect; rule out hemorrhage before thrombolytics.
    • Labs and tests: baseline platelets, INR; ECG to identify AFib or structural heart disease as a source; glucose level (hypoglycemia can mimic stroke symptoms).
    • Other monitoring: oxygenation, airway support, hemodynamics, metabolic status.
    • Acute treatment goals: restore blood flow rapidly to salvage the penumbra and minimize neurologic injury.

  • Thrombolytic therapy in acute ischemic stroke

    • Mainstay therapy: thrombolytics (fibrinolytics) to dissolve clot and restore perfusion when eligible.

    • Alteplase (tPA, Activase)

    • Dose: ext{Dose} = 0.9 ext{ mg/kg}, ext{ max } = 90 ext{ mg}

    • Administration: 10% as IV bolus over 1 minute; remaining 90% as IV infusion over 60 minutes.

    • Historical trial background: NINDS trial (1995) showed improved 3-month outcomes with alteplase in patients within 3 hours of onset, but higher symptomatic intracranial hemorrhage (ICH) risk (6.4% vs 0.6% in placebo).

    • Extended window evidence: ECASS III extended the window to 4.5 hours with stricter inclusion/exclusion criteria (e.g., age < 80, no prior stroke or diabetes, significant NIHSS, no prior anticoagulant use).

    • Tenecteplase (TNK-tPA)

    • Advantages: higher fibrin specificity; single IV bolus dosing over 5 seconds; potentially faster administration.

    • Evidence: ACT trial showed similar efficacy and safety to alteplase; FDA approved for acute ischemic stroke.

    • Time windows and eligibility

    • Standard window: within 0–3 hours of symptom onset for thrombolysis.

    • Expanded window: 0–4.5 hours under stricter exclusions (e.g., age < 80, no prior stroke or diabetes, significant NIHSS, not on oral anticoagulants).

    • Stroke team activation and streamlined processes aim to minimize door-to-needle time; the general goal is to initiate treatment as soon as criteria are met and safety is established.

    • Eligibility criteria for thrombolytics (summary from the lecture)

    • Age ≥ 18 years; clinically definite ischemic stroke with measurable deficit.

    • Onset to treatment time within 0–3 hours (or 0–4.5 hours with extended criteria).

    • Blood pressure ≤ 185/110 mmHg (or lowered to below threshold if elevated).

    • Glucose level > 50 mg/dL.

    • No intracranial hemorrhage on imaging; no major bleeding risk; no recent intracranial surgery or head trauma within a defined window; no GI bleed within 3 weeks; no recent major surgery.

    • Platelets > 100,000/mm^3; INR < 1.7; no recent therapeutic-dose LMWH within 24 hours.

    • No known coagulopathy or active bleeding; not on other anticoagulants that would raise bleeding risk.

    • Blood pressure management around thrombolysis

    • If eligible for thrombolysis: target blood pressure < 185/110 mmHg, achievable with IV antihypertensives (e.g., labetalol, clevidipine, nicardipine); maintain below threshold for 24 hours after thrombolytic administration.

    • If not receiving thrombolysis: tolerate higher blood pressure unless > 220/120 mmHg; aim for only ~15% reduction in first 24 hours if treated conservatively.

    • Post-thrombolysis monitoring and safety

    • Avoid all other anticoagulants and antiplatelets for at least 24 hours post-thrombolysis.

    • Frequent neurologic assessments (e.g., NIHSS) to monitor response and detect hemorrhagic transformation or deterioration.

    • If there is clinical improvement, continue monitoring; any new/worsening deficits may indicate hemorrhagic conversion or lack of efficacy.

    • Reversal and bleeding management if symptomatic intracranial hemorrhage occurs

    • Broad categories of reversal strategies (illustrative, not exhaustive):

      • Cryoprecipitate; platelets for thrombocytopenia; prothrombin complex concentrate (PCC); fresh frozen plasma (FFP); vitamin K for warfarin reversal.
      • Antifibrinolytics (aminocaproic acid, tranexamic acid) when appropriate and not contraindicated.
      • Recombinant factor VIIa (rFVIIa) is listed as unclear and generally not preferred due to risk; clinical judgment required.

    • Symptomatic ICH within 24 hours after thrombolysis is a high-risk event; management is time-sensitive and may involve one or more of the above reversal strategies.

    • Alternatives if thrombolysis is not indicated or not eligible

    • Mechanical thrombectomy: endovascular clot retrieval; can be used in selected large-vessel occlusions, sometimes in conjunction with or instead of thrombolysis.

    • Aspirin can be considered after the initial 24 hours if thrombolysis was not given or if clinically appropriate; thrombolysis should not be substituted by aspirin in eligible patients.

  • Acute ischemic stroke management: practical principles

    • Early imaging and neurologic evaluation are essential to differentiate ischemic vs hemorrhagic etiologies and to guide therapy.
    • For patients ineligible for thrombolysis, antiplatelet therapy (see secondary prevention) remains important.
    • Mechanical thrombectomy is an option for certain patients with large-vessel occlusion, either after thrombolysis or as an alternative.
    • Blood pressure and glucose control are important supportive aspects; avoid aggressive BP lowering if the patient is not candidates for thrombolysis unless indicated by guidelines.
    • VTE prophylaxis is important once bleeding risk subdues; mechanical prophylaxis is often used in the first 24 hours post-thrombolysis.

  • Secondary prevention: preventing another stroke after an initial ischemic event

    • For non-cardioembolic (atherosclerotic) stroke
    • Antiplatelet therapy is the cornerstone: options include
      • A) Aspirin alone (low-dose common);
      • B) Aspirin plus extended-release dipyridamole (Aggrenox);
      • C) Clopidogrel (Plavix).
    • Dual antiplatelet therapy (DAPT) after ischemic stroke is used only briefly (e.g., 3 weeks to 3 months depending on scenario) and is not equivalent to long-term DAPT used in acute coronary syndromes (ACS), which is typically at least 12 months.
    • Aggrenox specifics: extended-release dipyridamole is not crushable; GI side effects can be more common; aspirin/dipyridamole combination provides better protection than either agent alone.
    • For cardioembolic stroke (AFib and other heart-origin clots)
    • Anticoagulants are the mainstay: DOACs preferred for non-valvular AFib; warfarin remains standard for valvular AFib.
    • In patients with AFib who have had a prior stroke/TIA, anticoagulation is generally indicated unless contraindicated.
    • Reversals and interactions: discussed above for DOACs; warfarin reversal with PCC/FFP/vitamin K as needed.
    • Special considerations
    • If AFib is valvular (e.g., mechanical valve or significant mitral stenosis), DOACs are not recommended; warfarin is used.
    • If stroke was due to carotid disease or other vascular pathology, consider vascular interventions (carotid endarterectomy or carotid artery stenting) as indicated.

  • Practical reminders and clinical pearls from the lecture

    • “Time equals tissue”: faster reperfusion saves brain tissue; aim to treat as soon as safely possible.
    • Hypoglycemia can mimic stroke; always check glucose prior to thrombolysis.
    • The CHA2DS2-VASc risk score is specific to AFib stroke risk and should not be misapplied to VTE or ACS risk assessments.
    • DOACs have box warnings, drug interactions, and specific reversal strategies; not all DOACs are interchangeable in every patient; dose and renal function considerations are essential.
    • In AFib: valvular AFib uses warfarin; non-valvular AFib often uses DOACs; always consider patient-specific factors (comorbidities, interactions, tolerability, monitoring needs, cost).

  • Hemorrhagic stroke and other guidelines (brief mention)

    • There are distinct guidelines for spontaneous intracerebral hemorrhage and subarachnoid hemorrhage; management differs substantially from ischemic stroke and often involves controlling bleeding, preventing rebleeding, and addressing factors like hypertension and intracranial pressure.

  • Quick reference framework for study and exam preparation

    • Identify stroke type first: ischemic vs hemorrhagic.
    • Determine if thrombolysis is indicated using time window, BP, glucose, platelets, INR, and bleeding risk.
    • If eligible, choose alteplase or tenecteplase; know dosing basics and key trial evidence.
    • Monitor closely after thrombolysis; avoid anticoagulants/antiplatelets for 24 hours post-treatment.
    • Assess AFib risk with CHA2DS2-VASc for non-valvular AFib; decide on anticoagulation strategy accordingly.
    • For non-cardioembolic secondary prevention, select antiplatelet therapy (aspirin, Aggrenox, or clopidogrel) and understand dual therapy windows.
    • For cardioembolic secondary prevention, anticoagulation (DOACs preferred in non-valvular AFib; warfarin for valvular AFib).
    • Consider mechanical interventions for carotid disease when appropriate.

  • Important equations and values to memorize

    • Alteplase dosing: ext{Dose}_{ ext{alteplase}} = 0.9 rac{ ext{mg}}{ ext{kg}} ext{ (max 90 mg)}
    • Alteplase administration: 10% as bolus over 1 min; 90% as infusion over 60 min.
    • Expanded thrombolysis window (ECASS III) criteria include specific exclusions (e.g., age, diabetes, prior stroke) that limit eligibility to extend the window to 4.5 hours.
    • NEUROLOGIC deficit assessment: NIHSS scoring 0–42; higher scores indicate greater deficit and worse prognosis.

  • Ethical and clinical implications highlighted in the lecture

    • Balancing rapid reperfusion with bleeding risk requires careful patient selection and adherence to guidelines.
    • The decision-making process involves risk-benefit analysis, patient-specific factors (comorbidities, concomitant medications, renal function), and patient or surrogate preferences when feasible.
    • Public health impact: primary prevention can prevent up to ~80% of strokes through lifestyle modification, blood pressure control, lipid management, and smoking cessation.

  • Chronology and timeline concepts emphasized

    • Primary prevention → Acute ischemic stroke treatment → Secondary prevention (to prevent recurrence).
    • Time-sensitive nature of thrombolytic therapy; longer delays reduce benefit and increase risk.
    • Post-stroke care includes monitoring for neurologic changes, preventing complications, and initiating preventive strategies for future events.

  • Summary of practical take-home messages

    • Distinguish ischemic vs hemorrhagic stroke at presentation to guide therapy appropriately.
    • Use the CHA2DS2-VASc score to guide AFib anticoagulation decisions, remembering the special interpretation rule for the female sex point.
    • For eligible patients, alteplase or tenecteplase can be used within time windows, with careful monitoring for bleeding; after thrombolysis, avoid antithrombotics for 24 hours.
    • DOACs are generally preferred for non-valvular AFib; warfarin remains necessary for valvular AFib.
    • Secondary prevention relies on antiplatelets for non-cardioembolic strokes and anticoagulation for cardioembolic strokes; statins and lifestyle modifications are foundational across all primary/secondary prevention strategies.