BPHM2143 Stroke Lecture Notes PDF

BPHM2143 Pharmacy in Body System Series: Cardiovascular & Renal Stroke Janice Tam [email protected] Learning Outcomes Define stroke and understand its impact on public health. Identify and differentiate between the types of stroke: ischemic stroke, hemorrhagic stroke, and transient ischemic attack (TI...

BPHM2143 Pharmacy in Body System Series: Cardiovascular & Renal Stroke Janice Tam [email protected] Learning Outcomes Define stroke and understand its impact on public health. Identify and differentiate between the types of stroke: ischemic stroke, hemorrhagic stroke, and transient ischemic attack (TIA). Recognize the risk factors for stroke, including modifiable and non-modifiable factors, and explain the common causes of stroke. Understand the pathophysiology of ischemic and hemorrhagic stroke, including the processes of ischemia and hemorrhage. Apply the most recent ACC/ASA guidelines in the management of acute stroke, including initial assessment, diagnosis, and treatment options for both ischemic and hemorrhagic stroke. Describe the pharmacological management of acute stroke, including antithrombotic therapy, antihypertensive therapy, and other medications used in stroke management. Discuss the secondary prevention strategies for stroke, including lifestyle modifications, pharmacological interventions, and surgical interventions according to the most recent ACC/ASA guidelines. Introduction Sudden interruption of blood flow to a part of the brain ◦ result in damage / death of brain cells due to lack of oxygen and nutrients ◦ Infarction occurs in just a few minutes ◦ Stroke is the acute neurologic injury that occurs as a result Aka cerebrovascular accident (CVA) In HK, ◦ 4th most common cause of disability and death ◦ ~3000 deaths/year (3-months’ death rate 30%) ◦ > 50% survivors can fully resume self-care ability Classification Ischemic (88%) ◦ Diminished supply of arterial blood  reduced nutrients and oxygen to brain tissue Transient ischemic attack (TIA): predictor of ischemic stroke ◦ When blood flow is quickly restored, brain tissue can recover fully within 24h ◦ No evidence of infarction on brain imaging Hemorrhagic (12%, but higher mortality) ◦ Subarachnoid hemorrhage (SAH) ◦ bleeding into CSF within subarachnoid space (surrounds brain) ◦ Intracerebral hemorrhage (ICH) ◦ bleeding into brain parenchyma What is a Subarachnoid Haemorrhage – Head2Head. Oxford University Hospitals, 2024. Accessed 4 January, 2024. https://www.ouh.nhs.uk/head2head/subarachnoid-haemorrhage.aspx  Introduction The cerebral hemispheres. Brain Profiles and Personality Types, 2010. Assessed January 8, 2024. Functions of each part of brain. Solution Pharmacy, 2021. Assessed January 8, 2024. https://solutionpharmacy.in/functions-of-each-part-of-brain/ https://www.semanticscholar.org/paper/BRAIN-PROFILES-AND-PERSONALITY- TYPES/d78ede8db0999bd91d23a11c03153c98ff1d48fa  10% 2% 88% 13% 23% 27% 35% 3% Occlusion to Embolism Cerebral E.g. small arteries from heart ischemia of vasospasm, in brain’s deep (e.g. Atrial unknown migraine structures fibrillation) origin Chapter 39. Stroke, Attridge RL, Miller ML, Moote R, Ryan L. Internal Medicine: A Guide to Clinical Therapeutics; 2013. Available at: https://accesspharmacy.mhmedical.com/content.aspx?sectionid=42003755&bookid=565&Resultclick=2 Accessed: January 02, 2024 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association Ischemic vs. Hemorrhagic Stroke Healthline, 2024. Accesses January 3, 2024. https://www.healthline.com/health/stroke/bells-palsy-vs-stroke#takeaway Brain Ischemia Thrombosis: in-situ artery obstruction ◦ Due to diseases arterial wall e.g. atherosclerosis ◦ Small vessel occlusion  lacunar infarcts Embolism: debris originate elsewhere ◦ Source of embolism needs to be treated ◦ Multiple affected sites if cardiogenic Systemic hypoperfusion: reduced perfusion ◦ Inefficient heart pumping ◦ Cardiac arrest / arrhythmias ◦ Reduced cardiac output ◦ Acute myocardial ischemia / pulmonary embolism / bleeding What is a “Mini” stroke? Health Matter – New York- Presbyterian, 2024. Accesses January 3, 2024. https://healthmatters.nyp.org/what-is-a-mini-stroke/  Risk Factors (Ischemic Stroke) Non-modifiable Modifiable ◦ Age > 55yo ◦ HTN / heart diseases ◦ Gender ◦ Atrial fibrillation ◦ Ethnicity: higher mortality in Blacks ◦ Smoking / alcohol / illicit drug use ◦ Family history ◦ DM / hyperlipidemia ◦ Prior stroke/TIA/MI ◦ Diet / obesity / physical inactivity ◦ Prior TIA has 10X higher risk having stroke ◦ Sleep apnea ◦ Carotid / Peripheral artery diseases ◦ Estrogen ◦ Especially >50mcg in OC ◦ HRT(27-39% increase risk) Brain Hemorrhage SAH ◦ Blood spreads quickly within CSF  rapid increase in intracranial pressure ◦ Causes: rupture of arterial aneurysms from base of brain / vascular malformations ICH ◦ Bleeding usually from small arteries ◦ Hematoma gradually enlarges over minutes to hours and destroys brain tissue ◦ Causes: uncontrolled HTN, illicit drug use (amphetamines and cocaine) Hemorrhagic Stroke. Essential Topics About the Imaging Diagnosis and Treatment of Hemorrhagic Stroke: A Comprehensive Review of the 2022 AHA Guidelines – ScienceDirect, 2022. Accessed January 3, 2024. https://www.sciencedirect.com/science/article/abs/pii/S0146280622002250  Mortality & Complications 30-days’ mortality Complications ◦ Ischemic strokes:16-23% ◦ Medical ◦ ICH: 32-52% ◦ Dysphagia  pneumonia ◦ SAH: 50% ◦ Others: ◦ 26% die before arriving ◦ fever, GIB, DVT, PE / VTE, UTI, falls/fractures, hospital; 13% die in depression (29%) hospital ◦ Cardiac ◦ MI (1-2.5% of acute stroke), arrhythmias (25% in first 72 hrs), cardiomyopathies ◦ Neurological Brain hernia ◦ Cerebral edema, elevated intracranial pressure, brain herniation, hemorrhagic transformations ◦ Seizures Hemorrhagic Transformation Common complication with acute ischemic stroke (10-40%) Bleeding within an area of brain affected by an ischemic stroke ◦ Occurs when bleeding infarction after blood flow restored ◦ Exacerbated by reperfusion therapies (thrombolysis and thrombectomy) ◦ DC anti-thrombotics might be needed ◦ Appears as cerebral hemorrhage on radiological images Associates with increased mortality and morbidity Initial Clinical Presentation F.A.S.T warning signs ◦ F = face drooping ◦ A = arm weakness ◦ S = speech difficulty ◦ T = time to call 999 Others ◦ Unilateral weakness ◦ Confusion ◦ Impaired vision ◦ Loss of balance ◦ Severe headache Initial Stroke Management Initial Assessment 1. Medical stability ◦ ABC: airway, breathing, circulation 2. History & Physical ◦ Onset of ischemic stroke (94%) mmol/L] Fluids Swallowing assessment ◦ Volume depletion is common ◦ Prevent aspiration pneumonia (NPO PRN) ◦ Use NS ̶ hypotonic may exacerbate cerebral edema Head of bed elevation (30o) ◦ If ↑intracranial pressure / aspiration risk Fever ◦ Early mobilization (within 24hrs onset) ◦ Treat source maybe harmful ◦ Antipyretics (paracetamol) PRN Stroke care unit Hemorrhagic Stroke Management  Blood Pressure Management Excessive BP reduction in acute phase may compromise cerebral perfusion  induce ischemia 2023 AHA/ASA (subarachnoid hemorrhage) ◦ BP >180–200 mmHg: gradual reduction with MAP risk) ◦ Also angioedema, reperfusion injury ◦ Routine head CT/MRI to confirm no hemorrhage at 24h after alteplase before anticoagulants or antiplatelets ◦ Not recommended for mild, non-disabling stroke NIHSS 0-5 (Class III: No benefit) Acute Ischemic Stroke  NIHSS AHA/ASA 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack Disabling stroke symptoms REFERENCE Reperfusion IV fibrinolysis ◦ Tenecteplase: single bolus, longer duration of action ◦ NOT approved for acute ischemic stroke (alternative) ◦ Compared to alteplase: ◦ Increased ICH ; lower favorable outcome and higher mortality ◦ Can be used in patients eligible for mechanical thrombectomy Acute Ischemic Stroke  REFERENCE Reperfusion Mechanical Thrombectomy (MT) ◦ For large artery occlusion and can be treated within 6 or 6-24 hours ◦ Can be used alone or in addition to IV alteplase for same event if candidate for both ◦ Do not delay MT for observing clinical response to alteplase Acute Ischemic Stroke  Blood Pressure Management Acute ischemic stroke (< 72hrs) (2017 ACC/AHA HTN guideline) ◦ Early initiation or resumption of antihypertensive ONLY: 1. tPA (risk of ICH if BP too high) ◦ Lower to 3) Stroke due to large artery atherosclerosis Low-risk TIA (ABCD2 score < 4) High-risk TIA (ABCD2 score ≥ 4) SAPT Regimen: (not within 24 hr of t-PA) Aspirin 160-325mg within 24-48 hrs onset, followed by 50-325mg daily DAPT Regimen: Aspirin (160-325 mg loading dose, followed by 50-100 mg daily); plus Clopidogrel (300-600 mg loading dose, followed by 75 mg daily) If cardioembolic, refer to anticoagulant section. Acute Ischemic Stroke  Anticoagulant Urgent full-dose parenteral (UFH/LMWH) anticoagulation in AIS generally NOT recommended (Class III; No benefit) ◦ Acute cardioembolic stroke OR TIA with clear anticoagulation indication (e.g AF, VTE, mechanical heart valve)  unproven benefit of anticoagulation Patient already on anticoagulant: withhold at onset of AIS; restart when stable Triple therapy (i.e. anticoagulant + DAPT)  AVOID (high risk of hemorrhage) Not in Acute Ischemic Stroke Acute Ischemic Stroke VTE Prophylaxis For ALL patients with AIS and restricted mobility 1. Pharmacologic + IPC (on admission): a) IV thrombolysis: delay anticoagulation until 24h after thrombolysis b) No thrombolysis AND no DAPT: low-dose heparin (UFH/LMWH) c) Already on anticoagulation: low-dose heparin when therapeutic anticoagulation is withheld; stop when oral anticoagulation is therapeutic 2. DAPT: IPC alone Low-dose heparin: use UFH or LMWH ◦ E.g. Enoxaparin 40 mg SC once daily (low-dose) Enoxaparin 1 mg/kg SC every 12 hours (full-dose) Acute Ischemic Stroke HK Scenario for AIS 24-hr intravenous thrombolysis (IVT) service in all acute HA hospitals 24-hr intra-arterial thrombolysis (IAT) service in selected ◦ IAT: t-PA directly into the affected artery using a catheter ◦ Less common than IVT (used when IVT CI or large clot) Pre-hospital stroke screening with Fire Service Department ◦ 2018 pilot project; trained EMS personnel ◦ Shorten onset-to-door time ◦ Shorten door-to-CT time ◦ Shorten door-to-needle time ◦ Shorten door-to-MT time HK Scenario for AIS EMS performance pledge 12 min for 92.5% of calls For reperfusion Onset-to-needle: ~ 2.5 hrs (longest 4.5h) Onset-to-MT: ~ 4 hrs (longest 6.5h) Ischemic Stroke Prevention PRIMARY PREVENTION Primary Prevention For prevention in patients who never had ischemic stroke Same as primary prevention for cardiovascular disease (CVD) ◦ Modifiable risk factors ◦ Smoking cessation ◦ Weight control / diet / exercise ◦ Dyslipidemia ◦ Hypertension ◦ Diabetes mellitus Ischemic Stroke Ischemic Stroke + TIA Prevention SECONDARY PREVENTION Secondary Prevention Risk Factors / LSM Antithrombotic therapy ◦ Antiplatelet: SAPT for long-term ◦ Anticoagulation: only if cardioembolic source Blood Pressure Hyperlipidemia Diabetes: goal HgbA1C aspirin) ◦ Aspirin 50-325 mg daily (22% reduction in ischemic strokes) ◦ Clopidogrel 75 mg daily (If intolerant to aspirin) ◦ Might be slightly more effective than aspirin alone (CAPRIE trial) ◦ Aspirin + dipyridamole ER 25 mg/200 mg twice a day (combo not in HK) ◦ Might be slightly more effective than aspirin alone (ESPRIT trial) ◦ Similar efficacy to clopidogrel (PRoFESS trial) ◦ DAPT: long-term use no benefit over SAPT but increased major bleeding (MATCH study) Cardiogenic embolism (e.g. AF, mechanical heart valves) ◦ Long-term anticoagulation with warfarin or DOAC ◦ Refer to Atrial Fibrillation lecture Ischemic Stroke Blood Pressure First-line ◦ Thiazide ◦ ACEI / ARB Other antihypertensive agents ◦ CCB not first-line in 2o prevention as limited data (1st line in primary hypertension) ◦ Other agents can be used for addition BP goal < 130/80 mmHg Ischemic Stroke Hyperlipidemia Mediterranean diet High-intensity statin ◦ 2018 AHA/ACC recommendation ◦ Atorvastatin 80mg daily or Rosuvastatin 20mg daily ◦ only titrate down if unable to tolerate ◦ For patients with no CHD, no cardioembolic source+ LDL>100mg/dL [2.6 mmol/dL] Goal: (refer to Lipid lecture) ◦ Patients with atherosclerosis: LDL < 70mg/dL [1.8 mmol/dL] ◦ Statin + ezetimibe (if needed) ◦ Very high risk on max statin + ezetimibe ◦ if LDL still > 70 mg/dLPCSK9 inhibitor TG: icosapent ethyl 2g BD is reasonable to reduce recurrent stroke ◦ if already taking moderate-high intensity statin Ischemic Stroke Scores and Scales Recap ICH / FUNC: used in grading of ICH HH/WFNS: used in grading of SAH NIHSS: to assess severity of stroke (initial assessment) ABCD2: to assess stroke risk in TIA patients GCS: measures level of consciousness (not specific to stroke) Modified Rankin scale: ◦ Measures degree of disability and dependence in patients who had stroke ◦ Will see in literature as measurement of recovery Reference American Stroke Association. American Heart Association 2024. Accessed January 4, 2024. https://www.stroke.org/en/ Benjamin EJ, Virani SS, Callaway CW, et al. Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association. Circulation. 2018;137(12):e67-e492. doi:10.1161/CIR.0000000000000558 Kaplan, LR. Stroke: Etiology, classification, and epidemiology. UpToDate, 2023. Accessed January 3, 2024. https://www-uptodate- com.eproxy.lib.hku.hk/contents/stroke-etiology-classification-and- epidemiology?search=stroke&source=search_result&selectedTitle=4~150&usage_type=default&display_rank=4 Leung et al. Pre-hospital stroke screening and notification of patients with reperfusion-eligible acute ischaemic stroke using modified Face Arm Speech Time test. Hong Kong Med J 2020 Dec;26(6):479–85 | Epub 7 Dec 2020 Smith WS, Johnston S, Hemphill, III J. Introduction to Cerebrovascular Diseases. In: Loscalzo J, Fauci A, Kasper D, Hauser S, Longo D, Jameson J. eds. Harrison's Principles of Internal Medicine, 21e. McGraw Hill; 2022. Accessed January 02, 2024. https://accesspharmacy-mhmedical- com.eproxy.lib.hku.hk/content.aspx?bookid=3095&sectionid=265448020 Stroke. Smart Patient. Hospital Authority, 2024. Accessed 2 January, 2024. https://www21.ha.org.hk/smartpatient/SPW/en-us/Disease- Information/Disease/?guid=29ac1219-3d68-4378-a2bd-09e111da3650 Tsang, A. C., Yeung, R. W.,Tse, M. M., Lee, R., & Lui, W. M. (2018). Emergency thrombectomy for acute ischaemic stroke: current evidence, international guidelines, and local clinical practice. Hong Kong Medical Journal = Xianggang Yi Xue Za Zhi, 24(1), 73-. https://doi.org/10.12809/hkmj176296 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association