Stroke Pharmacotherapy and Case-Based Decision Tree Notes

Ischemic Stroke: Overview, Assessment, and Acute Management

• Recap of session plan: finish ischemic and hemorrhagic stroke slides, build a decision tree, practice cases, review VTE if time, and discuss practical implications for patient care and access to medications.
• Do not memorize every DOAC dose; focus on understanding benefits/shortcomings, renal dose adjustment, reversal agents, drug interactions, and indications for specific contexts.
• Key takeaway about DOACs: they require renal adjustment and may have reversal agents; dosing specifics depend on indication and patient factors. For Lovenox (enoxaparin) and Auryxtra (fondaparinux), doses are important to memorize. Dosing for DOACs is generally not required for exams here.
• Big picture questions to answer in practice: Is the stroke ischemic or hemorrhagic? If ischemic, is the patient a candidate for thrombolysis or thrombectomy? If hemorrhagic, how to manage bleeding and complications? What secondary prevention is appropriate?

Ischemic Stroke: Acute Pathway and Decision Points

• Initial assessment goals: identify risk factors, determine cause (etiology), and assess what in past medical history/med list may affect acute treatment (e.g., anticoagulants, antiplatelets).
• Key information to collect and consider:
  • Risk factors: age, race, family history; social history (tobacco, alcohol, drugs, diet, exercise); comorbidities (hypertension, diabetes, dyslipidemia); current meds.
  • Objective data: labs (hemoglobin/hematocrit, INR, APTT, platelets), neuro exam, brain imaging, ECG (look for AFib).
• Stroke etiology assessment: cardioembolic vs non-cardioembolic; if non-cardioembolic, underlying etiology often atherosclerosis.
• Blood pressure (BP) considerations:
  • Before thrombolysis, target < $185/110$ (mmHg) to be eligible for thrombolytic therapy.
  • Normal BP goal for general hypertension management is around <130/80, but for thrombolysis eligibility we aim for <185/110.
  • If not giving thrombolytics, BP may be allowed to remain higher (up to around $220/\text{diastolic not specified}$ in lecture notes; exact values vary by protocol).
• Blood glucose: aim to avoid hypoglycemia and hyperglycemia; monitor and manage to avoid adverse outcomes. Threshold mentioned: glucose should be greater than $50\text{ mg/dL}$ for thrombolysis eligibility.
• Imaging prerequisites: brain imaging before thrombolysis to exclude mimics and hemorrhage (e.g., tumors, aneurysm, hemorrhagic stroke).
• Thrombolysis options: alteplase or tenecteplase (when eligible).
• Other acute options: aspirin within $24-48\text{ h}$ if thrombolysis not given or contraindicated; consider mechanical thrombectomy in eligible patients.
• VTE prophylaxis in acute stroke: consider, but avoid pharmacologic prophylaxis while hemorrhagic risk is present or until bleeding is controlled.
• Nutrition: initiate appropriate nutrition plan.
• Acute plan components: alteplase/tenecteplase, aspirin (if not given thrombolysis), VTE prophylaxis, nutrition, and close monitoring.
• Monitoring after thrombolysis: frequent neurologic assessments (every 15 minutes initially, then every 30 minutes, then every hour as time since administration increases).
• Secondary prevention considerations after acute management: address risk factors (hypertension, diabetes, lipids, lifestyle), evaluate carotids for possible interventions, and plan education and referrals.
• Important equipotential questions during case discussions: Ischemic vs hemorrhagic stroke; eligibility for thrombolysis; whether thrombectomy is indicated; what secondary prevention is appropriate given stroke etiology.

Anticoagulants and Reversal: Quick Reference Notes

• General principle: memorize that DOAC dosing is not the focus here; know whether a DOAC has renal considerations and whether reversal agents exist.
• Reversal agents by agent class:
  • Dabigatran: Praxbind (idarucizumab)
  • Factor Xa inhibitors: Andexxa (coagulation factor Xa inhibitor reversal)
  • Warfarin: PCC (prothrombin complex concentrate) or FFP (fresh frozen plasma); vitamin K IV when appropriate
  • Unfractionated heparin or LMWH: protamine sulfate
• Doses for reversal and timing depend on the specific agent, indication, and bleeding risk; know the general approach rather than memorizing exact reversal doses.

Hemorrhagic Stroke: Intracerebral and Subarachnoid

• Intracerebral hemorrhage (ICH): bleeding within brain tissue, linked to hypertension, AV malformations, clotting disorders, tumors; presents with sudden focal deficits and often severe headache; prognosis generally worse than ischemic stroke.
• Subarachnoid hemorrhage (SAH): bleeding into the subarachnoid space, most commonly due to ruptured aneurysm; thunderclap headache is classic; may have stiff neck, photophobia, loss of consciousness; sentinel leak may precede rupture.
• ICP and management in ICH:
  • Avoid pharmacologic anticoagulants/antiplatelets in uncontrolled intracranial bleeding; use mechanical VTE prophylaxis initially.
  • Blood pressure management and glucose control are important but vary by situation.
  • Seizure management if seizures occur; dysphagia screening for swallowing safety; targeted temperature management not discussed here.
  • Intracranial pressure (ICP) management options include mannitol (osmotic diuretic) and hypertonic saline (3% saline); head-of-bed elevation to 30 degrees can help reduce ICP.
  • Steroids are not indicated for routine ICP reduction in hemorrhagic stroke (not primarily inflammatory).
• Specific SAH management:
  • Aneurysm securing: surgical clipping or endovascular coiling to prevent re-bleed.
  • Seizure prophylaxis in some cases; early prophylaxis may be used for up to a week in acute phase.
  • Vasospasm prevention and treatment: nimodipine (a calcium channel blocker) reduces cerebral infarction and poor outcomes; typical dosing: $60\text{ mg PO every }4\text{ h for }21\text{ days}$.
  • Other strategies to manage vasospasm: induced hypertension, balloon angioplasty, intra-arterial vasodilators.
• Summary for hemorrhagic stroke: avoid anticoagulants/antiplatelets; manage BP and glucose; ICP management; treat seizures; aneurysm-specific therapies for SAH; nimodipine for vasospasm prophylaxis.

Prevention: Primary and Secondary Stroke Prevention

• Primary prevention (general population):
  • Modifiable risk factor management: hypertension control, lipid management, diabetes control, diet, exercise, weight management, sleep, reducing tobacco/alcohol/drug use.
  • Statin therapy for primary prevention when indicated by risk groups (e.g., LDL > 190, clinical ASCVD, diabetes in 40-79, high 10-year ASCVD risk ≥ 7.5%).
  • Low-dose aspirin consideration for high cardiovascular risk in primary prevention; otherwise, aspirin may cause more harm than benefit in low-risk individuals.
• Atrial fibrillation (AFib) and primary prevention: CHADS-VASc risk scoring used to determine need for anticoagulation in AFib patients. AFib categories:
  • Valvular AFib vs non-valvular AFib (mitral stenosis or mechanical valves vs others).
  • In valvular AFib, warfarin is the primary option.
  • In non-valvular AFib, DOACs are typically preferred, though individual factors and HAS-BLED score must be considered; CHADS-VASc helps determine risk threshold for anticoagulation.
  • CHADS-VASc components (for non-valvular AFib):
  • C: congestive heart failure (CHF)
  • H: hypertension
  • A: age ≥ 75 (2 points) // age 65-74 gets 1 point
  • D: diabetes mellitus
  • S: prior stroke/TIA/thromboembolism (2 points)
  • V: vascular disease (MI, PAD, aortic plaque)
  • A: age 65-74 (1 point)
  • S: sex category (female) (1 point)
  • Score interpretation (per lecture):
  • 0 points: low risk; no anticoagulation; monitor
  • 1 point: moderate risk; consider anticoagulation with DOACs favored in many guidelines; individualize
  • ≥2 points: high risk; DOACs/anticoagulation generally recommended; valvular AFib has special considerations
• Secondary prevention after ischemic stroke (non-cardioembolic vs cardioembolic):
  • Non-cardioembolic ischemic stroke (atherosclerotic):
  • Blood pressure control; diabetes control; lifestyle modification; lipid management with statins due to ASCVD risk.
  • Lipids: statin therapy indicated if ASCVD is present (clinical ASCVD) or risk groups are met; in secondary prevention, statins are generally indicated for ASCVD risk reduction.
  • Antiplatelet therapy options: aspirin, clopidogrel, or aspirin plus dipyridamole (Aggrenox) depending on patient factors and tolerability.
  • Cardioembolic ischemic stroke (AFib):
  • Primary secondary prevention is anticoagulation: non-valvular AFib typically treated with DOACs or warfarin; valvular AFib remains warfarin-based.
  • If AFib is present, CHADS-VASc scoring is superseded by the need for anticoagulation in most cases, given stroke risk.
  • Lipids: may be less central if stroke is cardiogenic, but ASCVD risk factors still require management.
• Case-based reminders: atherosclerotic risk factors and AFib influence prevention strategy; HAS-BLED helps assess bleeding risk when considering anticoagulation.

Decision Tree Concepts for Stroke Pharmacotherapy

• Purpose: to guide the clinician through prevention, acute management, and secondary prevention across cornerstone stroke scenarios.
• Core decision points:
  • Primary prevention vs acute management vs secondary prevention
  • If AFib is present, valvular vs non-valvular AFib and CHADS-VASc scoring; HAS-BLED for bleeding risk
  • Ischemic vs hemorrhagic stroke in the acute setting
  • Thrombolysis eligibility: time since onset, BP, platelets, INR, glucose, recent surgery, intracranial hemorrhage history, active bleeding, anticoagulant use, and other exclusions
  • Eligibility for thrombectomy based on imaging and clinical criteria
  • Secondary prevention strategy based on stroke etiology (cardioembolic vs non-cardioembolic) and risk factor profile
• Example pathways:
  • Ischemic stroke + thrombolysis eligible: administer alteplase or tenecteplase after BP and bleeding risk assessment; monitor closely post-infusion; then begin appropriate secondary prevention (antiplatelet or anticoagulant depending on etiology).
  • Ischemic stroke not eligible for thrombolysis: manage BP to maintain perfusion; consider antiplatelet therapy; assess for thrombectomy if eligible; implement secondary prevention.
  • Hemorrhagic stroke: avoid anticoagulants/antiplatelets; manage BP/ICP; treat seizures; if SAH, secure aneurysm (clipping or coiling); nimodipine for vasospasm prevention.

Case Study Walkthrough: Ischemic Stroke, AFib Present vs Absent

• Case setup (baseline): patient presents with focal deficits (e.g., right arm weakness, facial droop); time since onset approximately two hours; CT shows ischemic stroke; ECG shows normal sinus rhythm; no AFib documented initially; BP is elevated; history includes hypertension and diabetes; Hb/Hct and platelets within normal limits; glucose around 145 mg/dL (post-meal).
• Primary prevention assessment (pre-hospital/long-term):
  • General population strategies apply: manage hypertension, lipids, diabetes; diet/exercise; sleep; avoidance of tobacco/alcohol; consider statin if risk groups met (ASCVD risk factors) and aspirin only if high cardiovascular risk.
  • If AFib suspected or known, CHADS-VASc and HAS-BLED should inform primary prevention strategy; DOACs often favored for non-valvular AFib.
• Acute management: ischemic stroke with time window ~2h15m; eligibility for thrombolysis depends on BP (< $185/110$ after stabilization) and other criteria (platelets > $100{,}000$, INR < 1.7, glucose > $50\text{ mg/dL}$, no recent bleeding, etc.).
  • In this case, BP is elevated; plan is to lower BP with IV antihypertensives (e.g., labetalol, nicardipine, clevidipine) to < $185/110$ before thrombolysis.
  • Time since onset: 2h15m is within the standard window (0–3 hours) for thrombolysis; extended window up to 4.5 hours exists but with additional exclusions (age > 80, prior stroke/diabetes, active anticoagulant use, etc.).
  • If thrombolysis is successful and BP remains controlled, begin post-thrombolysis monitoring: neurologic checks every 15 minutes initially, then hourly as time passes.
  • Post-acute secondary prevention for non-cardioembolic AFib absent: address risk factors and start antiplatelet therapy or anticoagulation based on risk; statin therapy considered due to ASCVD risk factors; blood pressure, diabetes, lipids, diet/exercise—addressed.
• Case variant with AFib present (new AFib diagnosed, non-valvular):
  • Primary prevention would now include CHADS-VASc scoring and consideration of DOAC/warfarin due to AFib; CHADS-VASc in this case would yield a higher risk score (e.g., 3 when counting female sex and hypertension and diabetes).
  • If AFib is newly diagnosed, HasBLED score informs bleeding risk; AFib patients generally require anticoagulation to prevent recurrent cardioembolic stroke unless contraindicated.
  • Acute management remains thrombolysis eligibility the same, with extra attention to DOAC use and timing; if on a DOAC, adjust strategy for thrombolysis per local guidelines and reversal considerations.
  • Secondary prevention becomes cardioembolic: anticoagulation (DOAC or warfarin) is indicated; lipid management remains guided by ASCVD risk; aspirin alone is less favored for cardioembolic AFib.
• Practical takeaways from the case exercise:
  • The decision tree helps organize when to pursue thrombolytics, antiplatelets, or anticoagulants based on etiology and timing.
  • In AFib, secondary prevention predominantly relies on anticoagulation; the presence of AFib changes the downstream prevention strategy even if the acute stroke was ischemic due to atherosclerotic disease.
  • Dosing specifics for DOACs are not required on the exam here, but be prepared to recognize reversal agents and when to initiate anticoagulation in AFib.
  • Always consider HAS-BLED versus stroke risk when deciding on anticoagulation in AFib.

Key Formulations, Thresholds, and Practical Details (LaTeX-formatted)

• Time windows for thrombolysis: $t_{onset} <br />\nobreak o <br />\nobreak 3 ext{ hours}$ (standard window); extended window up to $4.5 ext{ hours}$ with additional exclusions: older age (e.g., >80), prior diabetes/stroke, on oral anticoagulants, etc.
• Blood pressure thresholds:
  • Before thrombolysis: BP < 185/110 mmHg
  • Normal BP goal for primary prevention: BP
    ightarrow <130/80 mmHg
  • Unclear diastolic specifics when not thrombolyzing in lecture; management is case-by-case with IV agents to reach target.
• Platelet count: threshold for thrombolysis eligibility: ext{platelets}
  < 100{,}000 (i.e., < $100{,}000$ per microliter)
• INR threshold for thrombolysis: INR < 1.7
• Glucose threshold for thrombolysis: glucose > 50\,\text{mg/dL}
• Major BP-lowering IV agents used acutely: $ext{labetalol}, ext{nicardipine}, ext{clevidipine}$
• Antiplatelet therapy after ischemic stroke if not thrombolyzed: $6-48\,\text{hours}${$ after thrombolysis}}; options include $ext{aspirin}, ext{clopidogrel}, ext{Aggrenox}$ (aspirin + dipyridamole)
• Intracerebral hemorrhage management: avoid pharmacologic VTE prophylaxis initially; consider mechanical methods; manage BP and glucose; ICP management with $ext{mannitol}$ or $ext{hypertonic saline}$ (e.g., 3% saline); head-of-bed elevation to $30^{\circ}$; consider seizures management if present.
• Nimodipine for SAH vasospasm prevention: $60\,\text{mg} \;\text{PO every }4\,\text{h for }21\,\text{days}$; reduces symptomatic vasospasm and improves outcomes (34% reduction in cerebral infarction; 40% reduction in poor outcomes).
• Aneurysm management options for SAH: surgical clipping or endovascular coiling.
• VTE prophylaxis strategy in intracerebral hemorrhage: defer pharmacologic prophylaxis until bleeding is controlled; use mechanical devices in the meantime.
• Case-specific pharmacotherapy notes:
  • Three starred drugs for dosing in VTE exams include Lovenox (enoxaparin), warfarin, and fondaparinux; other DOACs are not required to memorize dosing for the quiz/exam here.

Practical Takeaways for Exam and Real-World Practice

• Always distinguish primary prevention, acute management, and secondary prevention when evaluating a stroke patient.
• Use CHADS-VASc for AFib risk stratification in non-valvular AFib; use HAS-BLED to assess bleeding risk when considering anticoagulation.
• For ischemic stroke, determine thrombolysis eligibility by time since onset, BP, platelets, INR, glucose, bleeding risk, and recent procedures; proceed with thrombolysis if eligible and BP is controlled.
• If thrombolysis is not feasible, consider thrombectomy where appropriate and initiate antiplatelet therapy while considering individual risk factors.
• In hemorrhagic stroke, avoid anticoagulants/antiplatelets; focus on controlling BP, ICP, and preventing seizures; aneurysm SAH requires securing the aneurysm and vasospasm preventive therapy.
• Always check for drug interactions, access to medications, and adherence issues; ensure proper handoffs and patient education for secondary prevention and follow-up.
• Use the decision-tree framework to structure case analysis, and be prepared to adapt the framework as new information becomes available (e.g., AFib status changes during a case).

Quick Reference: Common Acronyms and Terms

• AFib: atrial fibrillation
• DOAC: direct oral anticoagulant
• INR: international normalized ratio
• PCI: percutaneous coronary intervention (context not deeply covered here, but relevant for vascular risk)
• ASCVD: atherosclerotic cardiovascular disease
• Aggrenox: aspirin + dipyridamole combination
• HAS-BLED: bleeding risk score (not detailed here)
• NIHSS: National Institutes of Health Stroke Scale