12/4/2017. Disclosures. Objectives. Antiplatelet & Anticoagulant Considerations for Repair of Aneurysms And Reversal Options

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1 Antiplatelet & Anticoagulant Considerations for Repair of Aneurysms And Reversal Options Kiffon M. Keigher, MSN, ACNP-BC, BSN Rush University Medical Center Chicago, IL Disclosures The Joint Commission, Stroke Program Reviewer Cure 4 Stroke Foundation, Co- Founder & Board Member Objectives Describe indications for use of antiplatelets for neurovascular procedures Understand basic platelet aggregation process and binding of receptors List risk factors associated with antiplatelet use Name commonly used antiplatelet and anticoagulant medications and reversal options Describe considerations for patients prior to initiating antiplatelet therapies for unruptured and ruptured aneurysm repair 1

2 The Intracranial Aneurysm Key Considerations Ruptured vs Unruptured Size, location, morphology Risk Factors Hypertension Smoking Family History Mechanism: blood pressure tension of the wall exceeds the strength of wall itself Wall degeneration: pressure and sheer stress Inflammation is clearly associated with degenerated and ruptured walls Luminal thrombus Impaired endothelial function and high oxidative stress Starke, R. et al. The Role of Oxidative Stress in Cerebral Aneurysm Formation and Rupture. Current Neurovascular Research The Platelet DormantActive Activated platelets undergo 3 consecutive processes: 1. Shape change 2. Secretion 3. Aggregation Formation of platelet plug Activated platelets undergo 3 consecutive processes: 1. Shape change 2. Secretion 3. Aggregation Fibrinogen ADP 5 H-T 2

3 Formation of platelet plug Aggregation Final pathway of cross-linking of activated GPIIb/IIIa to macromolecules (primarily fibrinogen and vonwillebrand What Causes Platelet Activation? Blood Vessel Wall Injury Trauma Introduction of Catheters, GuideWires Placement of Implants HOW????? Endothelial Artery Wall Damage Multiple passes Inability to properly appose implant to artery wall Multiple attempts to resheath devices/implants Difficulty crossing the lesion Improper sizing of devices (too big) 3

4 Aneurysm Considerations Size and shape Small vs giant Saccular, fusiform, mycotic, dissecting Wide vs narrow neck Thrombosis within the sac Question to ask do we anticipate the need for stent assisted coiling or flow diversion for treatment? Indications for Antiplatelet Wide neck aneurysms Fusiform aneurysms Dissecting or Pseudoaneurysms Carotid or Vertebral artery stenosis Venous sinus stenosis or thrombosis Iatrogenic dissections Stroke TIA Fibromuscular dysplasia MoyaMoya syndrome Other bailout, coil prolapse Antiplatelets Indication Primary Prevention of ischemic stroke Ten year risk for CV disease is 6% or more High risk women over 65 yrs greatest benefit Asprin 81 mg preferred (minimize bleeding, no other antiplatelet agent have indications for primary prevention) Secondary prevention New stroke event-failed therapy TIA Prevention of thrombosis for placement of intraluminal stents Adverse Reactions Most common is bleeding Contraindications Active bleeding Known allergy could consider desensitization in some cases Goldstein et al., 2011) 4

5 Antiplatelets Interactions Medications that may synergistically increase bleeding risk Anticoagulants, NSAIDS, Herbals (gingko, ginger, ginseng) Monitoring Bleeding Drug Resistance More common with Clopidogrel vs aspirin Testing and dose adjustments varies among providers and organizations Accumetrics (VerifyNow) most common: ARU and PRU TEG and Rotem: provide measure of response to antiplatelet and relative hemorrhage or thrombotic risk, measure of hemostasis Other Considerations NSAID s in general best to avoid but no definitive interaction w/aspirin No clinically significant results showing should NOT use PPI with Clopidogrel. May be worse problem with known poor metabolizers Commonly Used Oral Agents Aspirin (Thromboxane inhibitor) Dose: 81 and 325 mg daily Considerations: Inhibits for life of platelet (5-7 days), GI bleed most common risk Clopidogrel (ADP Inhibitor) Dose: 75 mg daily (loading doses may vary from 150, 300, 600 mg) Considerations: Irreversible-inhibits for life of platelet (5-7 days). Pro-drug-CYP conversion to active metabolite, some patients may be resistant Aspirin/Dypirdamole(PDE Inhibitor) Dose: 200 mg/25 mg BID Considerations: Irreversible-inhibits for life of platelet. Up to 40% of patients will experience headaches Antiplatelets: Commonly Used Oral Agents High Potency P2Y12/ADP Inhibitors are: Both have ONLY acute coronary syndrome indications Ticagrelor Dose: Loading dose: 180 mg x1, followed by 90 mg BID, after 12 months can consider decreasing to 60 mg BID Considerations: Can be used with aspirin dose of mg only, contraindicated in patients w/history of ICH, shown to prevent stent thrombosis but in ACS patients only Prasugrel Dose: Loading dose: 60 mg x1, followed by 10 mg daily, except for patients <60kg dose is 5 mg daily Considerations: BLACK BOX WARNING TO BE USED IN PATIENTS WITH TIA OR STROKE, not recommended for patients >75yo. Take with daily aspirin mg tab Less commonly used (older drug) Ticolpidine (Adenosine diphosphate inhibitor) Dose: 250 mg BID Considerations: Pro drug CYP to convert to active metabolite. Irreversible for life of platelet. Associated with more adverse reactions: GI intolerance, neutropenia, aplastic anemia and thrombotic thrombocytopenic purpura (must monitor labs) 5

6 P2Y12 Clopidogrel Prasugrel Ticagrelor Cangrelor GPIIb/IIIa Abciximab Integrilin Aggrastat TXA 2 Aspirin Blocking P2Y 12 Receptors Inhibit ADP-Induced Platelet Activation Ticagrelor (oral) and cangrelor (IV) are nonthienopyridine reversible antagonist of P2Y 12 ADP receptor Source: Bhatt D. N Engl J Med 2007;357: Commonly Used IV Agents Both are GPIIb/IIIa Inhibitors Most commonly used during endovascular procedures for prevention of stent thrombosis and stroke prevention Abciximab Dose: 0.25 mg/kg bolus, followed by infusion at mcg/kg/min for 12 hours typical up to max dose of 10 mcg/kg. Short half life. Eptifibatide Dose: for ACS--180 mcg/kg bolus over 1-2 minutes, then IV drip of 2 mcg/kg/min up to 72 hours. Given concomitantly with heparin. Should be given with daily aspirin mg daily. Need to adjust dose for patients with renal disease Adenosine Diphosphate Inhibitor (ADP inhibitor) active drug---does NOT require metabolic conversion Cangrelor Dose: Bolus of 30mcg/kg, followed by infusion of 4 mcg/kg/min for at least 2 hours but no more than 4 hours (duration of procedure) Considerations: indicated for ACS only, not indicated for patient who have taken oral P2Y12 agent or with planned use of GPIIb/IIIa agent, must bridge to oral dose of ADP inhibitor, reversible half-life of 3-6 minutes Reversible. Common adverse reaction includes dyspnea and respiratory issues VERY EXPENSIVE!! Biggest Concern is for Bleeding: Close Monitoring in ICU Setting Crucial 6

7 Transition to Oral P2Y 12 Inhibitors C-Phoenix Study Design Anti-Platelet Protocol: Anticipating stent placement typically Pre-Operative Loading Dose--options: Aspirin 325mg and Clopidogrel 75mg daily for 5-7 days prior to endovascular procedure Aspirin 325mg and Clopidogrel 600mg once day before endovascular procedure Other=provider preference 7

8 Anti-Platelet Protocol Intra-operative Check if levels therapeutic via Point of Care Testing (pre stent placement) Decide if post-operative additional load dose is needed Determine if additional antiplatelet agent, such as Abciximab, needed for prevention of thromboembolic event Sub-therapeutic and concerns for thromboembolic complications: Consider additional drug: i.e. Reopro Load administered during procedure by MD Point of Care Testing Measures level of platelet inhibition provided by: Therapeutic Levels Are (target varies by institution): 1. Aspirin ARU < Plavix or other P2Y12 agent PRU <230 ARU=Aspirin Reaction Units PRU=P2Y12 Reaction Units Red Thrombus Vs.. White Thrombus Anticoagulation RED Thrombus=VENOUS=ANTICOAGULANT Fibrin rich clots Low Pressure, Slow Flow Can break into embolus move into systemic circulation Antiplatelet WHITE Thrombus=ARTERIAL=ANTIPLATELET Platelet rich clots High Shear Pressure, High Flow Interruption of blood flow causes ischemia and/or death 8

9 Anticoagulants Indications Prevention of cardioembolic stroke Nonvalvular atrial fibrillation Venous thromboembolism Mechanism: decrease clot formation via different pathways Decrease activation of Vitamin K dependent clotting factors (II, VII, IX, X) Direct thrombin and direct Xa inhibitors Adverse reactions Most common: bleeding Bruising Respiratory issues: dyspnea Contraindications Acute bleeding Severe organ impairment (renal and hepatic impairment) Interactions NSAIDS, antiplatelets, herbals Monitoring Monitor for bleeding, target INR Anticoagulation: To Bridge or Not To Bridge Considerations: Why Is the Patient on OAC? Mechanical heart valve Atrial Fibrillation VTE Other?? What is the larger risk? Hemorrhage vs Thromboembolic Monitoring Coagulation Studies: PT/INR, PTT EKG Hemodynamic and Neurological Assessments To Interrupt To Bridge Rechenmacher, S.J. et al. J Am Coll Cardiol. 2015; 66(12):

10 Anticoagulants: Common oral Warfarin vitamin K antagonist Dose: Variable titrate to INR 2-3 Antidote: : Vitamin K, FFP, PCC (prothrombin complex concentrate) Novel Oral anticoagulants: Indications include nonvalvular afib and VTE treatment Dabigatran direct thrombin inhibitor Dose: mg BID Rivaroxaban-direct Xa inhibitor Dose: 20 mg PO daily Apixaban-Direct Xa inhibitor Dose: mg PO BID Anticoagulant: IV Heparin Dose: variable depends on indication for therapy and adjusted to achieve goal PTT Half-life: 1.5 hour Mechanism of action: acts at multiple sites, binds to antithrombin III, inactivates thrombin and other clotting factors Reversal: Protamine Sulfate 1-1.5mg IV per 100 units of heparin. Max Dose is 50mg/dose. Rate 5mg/min 10

11 SAH & ICH: Correct Coagulopathies Antiplatelets: Any type Reversal Agents: No antidote, give platelets Heparin Reversal Agent: Protamine 1mg/100 units heparin, max dose 50 mg Warfarin: Vitamin K antagonist Half-Life: hour (variable) Reversal Agents: Vitamin K, Fresh Frozen Plasma (FFP), Prothrombin Complex Concentrate (PCC) Dabigatran: Direct Thrombin Inhibitor Half-Life: hours Reversal Agent: Idarucizumab-very $$$, PCC or Activated recombinant factor VII (rfvii) Rivaroxaban, Apixaban: Direct Xa Inhibitor Half-Life: 5-13 hours (Rivaroxaban), 8-15 hours (Apixaban) Reversal Agent: No Antidote, PCC or Activated recombinant factor VII (rfvii) Elective vs. Emergent Aneurysm Repair Opportunity to time procedure for the right time More time to educate patient and family Allows for time to discuss past medical history that may contraindicate or prompt further workup of antiplatelet therapy Provides time to give a soft load vs a large loading dose or to bridge with a drip No EVD s, tracheostomies, g-tubes or other invasive lines or procedures to consider Out-Patient Considerations Pending Procedures or Surgeries Dental procedures, colonoscopies, biopsies, etc Orthopedic or other invasive planned surgeries History of GI bleed or Peptic Ulcer Disease Not a contraindication but may need further workup Consider Protonix or other PPI prophylaxis Allergy to antiplatelets Chronic epistaxis Anticoagulant use for other medical condition Interrupt & Bridge or Not Triple therapy considerations

12 Acute Phase Considerations Coil vs Stent and Coil vs Flow Diversion vs Clipping???????? External Ventricular Drains Does patient have an EVD in place? Is it functional and draining well? Do you anticipate your patient will need an EVD? Timing of EVD vs starting antiplatelet Pending surgical procedures Will patient require additional surgeries during hospital stay? Tracheostomy, g-tube, VPS Other critical care issues Does patient have other underlying medical conditions concerning for increased risk of bleeding? Thrombocytopenia Profound anemia Acute blood loss--postoperative GI bleed Hypercoaguable disorder Hemophilia or other blood clotting issue (i.e. VonWillebrands) Post stroke-post IV tpa Nursing Implications Understanding the Therapy Administer all doses of anti-platelets Do not hold doses unless indicated Know what is indicated! Platelet Counts Punctures and procedures post IV antiplatelets, anticoagulants Monitoring Signs of bleeding Signs of thromboembolic events Neurological changes Know reversal agents Educating the Patient Do not skip doses, do not stop medications prematurely w/o first speaking to surgeon/interventionalist call if having procedures requiring stopping medication Do not double doses Maintain safety & educate on increased bleeding risks Educate to monitor for excessive bruising Review possible medication interactions Bruising risks Summary The platelet has many receptors allowing for different types of drugs to be effective platelet inhibitors Multiple indications for use of antiplatelets Endovascular procedures themselves contribute to endothelial wall damage Some patients may need to have their anticoagulation medications adjusted for treatment-must decide to bridge or not and determine triple therapy Treatment approach for the hemorrhagic stroke patient is often more conservative and has potential higher risk in setting of antiplatelet use Education of patient and families is critical 12

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