SCRN Medication Review. Susan M. Gaunt MS APRN ACNS-BC CCRN CNRN Gwinnett Medical Center
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1 SCRN Medication Review Susan M. Gaunt MS APRN ACNS-BC CCRN CNRN Gwinnett Medical Center
2 Objectives To explain the indications, contraindications, interaction, timing, dosing, side effects of: Thrombolytics Anticoagulants Antiplatelets Statins
3 Thrombolytics What thrombolytic is used in stroke? Tissue Plasminogen Activator r-tpa (Alteplase or Activase) What is the indication? Ischemic stroke What are the time windows? Within 3 hours of symptom onset American Stroke Association has endorsed it s use up to 4.5 hours in select cases
4 tpa Inclusion Criteria Diagnosis of ischemic stroke causing measurable neurological deficit Onset of symptoms < 3 hours of symptom onset Age 18 years E Jauch et al. (2013) ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 44:
5 tpa Absolute Contraindications: Significant head trauma or stroke < 3 months Symptoms suggesting SAH Arterial puncture at noncompressible site < 7 days History of intracranial hemorrhage Intracranial neoplasm, AVM, aneurysm Recent intracranial or spinal surgery Elevated B/P > 185/110 E Jauch et al. (2013) ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 44:
6 tpa Absolute Contraindications: Active internal bleeding Bleeding diathesis including, but not limited to: Platelet count < 100,000 Heparin within 48 hrs with elevated aptt Current use of anticoagulant with INR >1.7 or PT> 15 sec Current use of direct thrombin inhibitors or direct factor Xa inhibitors E Jauch et al. (2013) ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 44:
7 tpa Absolute Contraindications: Blood glucose < 50 mg/dl CT shows hypodensity in > 1/3 rd cerebral hemisphere E Jauch et al. (2013) ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 44:
8 tpa Relative Contraindications: With careful consideration, weighing risk versus benefit, tpa can be given despite 1 or more relative contraindications Only minor or rapidly improving stroke symptoms Pregnancy Seizure at onset Recent GI or GU hemorrhage < 21 days MI < 3 months E Jauch et al. (2013) ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 44:
9 tpa Inclusion for 3 to 4.5 Hour Window Diagnosis of ischemic stroke causing measurable neurological deficit Onset of symptoms within 3 to 4.5 hours of treatment E Jauch et al. (2013) ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 44:
10 tpa Relative Contraindications for 3 to 4.5 Hour Window Age > 80 years Severe stroke with NIHSS > 25 Taking an oral anticoagulant regardless of INR History of both diabetes and prior stroke E Jauch et al. (2013) ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 44:
11 tpa (Alteplase) Administration Mix sterile water and Alteplase/Activase using transfix transfer device. Do not shake. Total vial is 100 mg. Concentration is 1mg/ml. Maximum dose is 90 mg. Alteplase/Activase package insert
12 tpa Administration Total dose is 0.9 mg/kg. Withdraw and discard the amount NOT to be given to the patient. Alteplase/Activase package insert
13 tpa Administration Withdraw bolus dose (10% of total dose). Give over one minute. Infuse the remaining part of the total dose over one hour via IV pump. Goal is Door To Needle time within 60 minutes Alteplase/Activase package insert
14 Assessment Monitor vital signs and neuro checks: Every 15 minutes for two hours after start of t-pa, then Every 30 minutes for six hours, then Every hour for 16 hours Keep B/P < 180/105 Repeat CT or MRI at 24 hours prior to antiplatelet or anticoagulant use. E Jauch et al. (2013) ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 44:
15 Complications Intracerebral Hemorrhage: Severe Headache Neurological deterioration Sharp rise in B/P Nausea & vomiting What do you do? Stop tpa Stat CT of head Treatment? Cryoprecipitate 8-12 units FFP Platelets S. Pugh et al AANN Guide to the Care of the Hospitalized patient with Ischemic Stroke
16 tpa Complications Systemic hemorrhage Delay insertion of: NG tubes Foley catheters Arterial sticks Angioedema or allergic reaction Diphenhydramine (Benadryl) H2 Antagonists (Ranitidine or famotidine) Methylprednisolone (Solu-Medrol) S. Pugh et al AANN Guide to the Care of the Hospitalized patient with Ischemic Stroke
17 Antiplatelets Which antiplatelets are used for secondary prevention of stroke? Aspirin Plavix Aggrenox New IV antiplatelets (Glycoprotein llb/llla receptor blockers) under research: Tirofiban Eptifibatide Abciximab
18 American Stroke Association Guidelines on Antiplatelet Therapy Antiplatelets are not recommended within 24 hours of tpa Aspirin 325mg within hours (Class 1;Level of Evidence A) to prevent recurrent stroke Usefulness of clopidogrel is not well established (Class llb; Level of Evidence C) Doesn t produces maximal inhibition of platelet aggregation for approximately 5 days E Jauch et al. (2013) ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 44:
19 Aspirin Inhibits the enzyme cyclooxygenase, reducing production of thromboxane A2, a stimulator of platelet aggregation Stopping ASA suddenly may increase the risk of stroke Take with food to prevent GI upset Side effects: GI Bleed B. Cucchiara et al. Jan Up to Date; Antiplatelet therapy for secondary prevention of stroke 2013 Lexicomp
20 Clopidogrel Inhibits ADP-dependent platelet aggregation Similar benefit to aspirin when compared in the CAPRIE trial Dose: 75mg once daily Polymorphisms in hepatic enzymes may affect the ability of clopidogrel to inhibit platelet aggregation in some people Interacts with proton-pump inhibitors Side effects: Bleeding, rash B. Cucchiara et al. Jan Up to Date; Antiplatelet therapy for secondary prevention of stroke 2013 Lexicomp
21 Combination Therapy MATCH and SPS3 trial did not show benefit with combination long term therapy of aspirin and clopidogrel No significant reduction in cerebrovascular events Increased incidence of bleeding CHANCE trial in China was positive for shortterm dual therapy. The POINT trial in ongoing B. Cucchiara et al. Jan Up to Date; Antiplatelet therapy for secondary prevention of stroke
22 Aspirin-extended release dipyridamole Dipyridamole impairs platelet function by inhibiting the activity of adenosine deaminase and phosphodiesterase Twice daily dosing PRoFESS trial between Aggrenox and Plavix did not show superiority Side effect: Headache B. Cucchiara et al. Jan Up to Date; Antiplatelet therapy for secondary prevention of stroke
23 Antiplatelet Rescue/Reversal Aspirin Lab test: Salicylate level or Platelet inhibition Rescue: Platelet transfusion DDAVP (desmopressin) Plavix Lab test: Plavix inhibition Rescue: Platelet transfusion DDAVP M. George (2013) Antiplatelet & Anticoagulant Rescue/Reversal Policy Gwinnett Medical Center
24 Anticoagulation Anticoagulants: Unfractionated heparin Low Molecular Weight Heparin (LMWH) Thrombin Inhibitors: Dabigatran Direct Factor Xa Inhibitors: Rivaroxaban, Apixaban Vitamin K antagonists: Warfarin Imaging should be done to rule out hemorrhage before initiation of anticoagulation
25 Contraindications to Anticoagulation Within the first 24 hours of tpa Early anticoagulation is not recommended: In severe stenosis of the ICA To prevent early recurrent stroke For the management of non-cerebrovascular conditions with moderate to severe stroke E Jauch et al. (2013) ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 44:
26 Unfractionated Heparin Drip Dosing: Adjust drip per PTT results using weight based algorithm Reversal: Protamine M. George (2013) Antiplatelet & Anticoagulant Rescue/Reversal Policy Gwinnett Medical Center
27 Anticoagulation for Atrial Fibrillation Warfarin/Coumadin: Vitamin K antagonist Monitored by INR goal 2-3; dosing varies Vitamin K consistent diet Multiple drug interactions Reported as one of the highest number and most serious adverse drug events to the FDA Reversal/Rescue: Vit K FFP Plasminogen Complex Concentrate (PCC) Factor Vlla M. George (2013) Antiplatelet & Anticoagulant Rescue/Reversal Policy Gwinnett Medical Center
28 Anticoagulation for Atrial Fibrillation Dabigatran/Pradaxa: RE-LY trial: Direct thrombin inhibitor Peaks in 2 to 3 hrs; High-life 12 to 17 hours Twice daily dosing Renal elimination; renal dose less Traditional coagulation tests are not reliable Rescue: (Charcoal if within 2 hrs of ingestion) PCC +/- FFP Factor Villa (last resort) E Jauch et al. (2013) ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 44: M. George (2013) Antiplatelet & Anticoagulant Rescue/Reversal Policy Gwinnett Medical Center
29 Anticoagulation for Atrial Fibrillation Rivaroxaban/Xarelto: ROCKET AF trial Direct Factor Xa Inhibitor Half-life 5 to 9 hours Eliminated renal, fecal and hepatic; renal dose No INR monitoring or diet restrictions Once a day dosing 20 mg vs 15 mg renal dose No reliable way to measure pharmacodynamic effect Less hemorrhagic complications than Warfarin E Jauch et al. (2013) ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 44:
30 Anticoagulation for Atrial Fibrillation Apixaban/Eliquis: ARISTOTLE trial Direct factor Xa inhibitor Half-life is 5 to 9 hours No monitoring or special diet Less hemorrhagic complications than warfarin Cleared by the cytochrome P450 system No reliable test for measuring pharmocodynamics Do not discontinue abruptly without anticoagulant bridging. E Jauch et al. (2013) ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 44:
31 Anticoagulation for Atrial Fibrillation Rescue Rivaroxaban/Xarelto & Apixaban/Eliquis: Charcoal if within 2 hours of ingestion FFP Prothrombin Complex Concentrate M. George (2013) Antiplatelet & Anticoagulant Rescue/Reversal Policy Gwinnett Medical Center
32 DVT Prophylaxis Early mobilization decreases risk of DVT PREVAIL Trial: PREvention of VTE after Acute Ischemic Stroke with LMWH or enoxaparin once daily versus unfractionated heparin twice daily. The enoxaparin group had a 43% lower incidence of clots than the heparin group E Jauch et al. (2013) ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 44:
33 LMWH Enoxaparin Dosing: 40 mg once daily; Renal dose is 30 mg once daily Reversal (partial): Protamine 1 mg per 1 mg of LMWH Repeat 2 to 4 hours with 0.5 mg per 1 mg of LMWH M. George (2013) Antiplatelet & Anticoagulant Rescue/Reversal Policy Gwinnett Medical Center
34 Statins HMG CoA reductase (hydroxymethylglutaryl CoA reductase) inhibitors Benefits: plaque stabilization, reversal of endothelial dysfunction, and decreases thrombosis Daily dosing usually at bedtime Contraindicated in liver disease Side effects: Myopathy Elevated Liver enzymes Dizziness, nausea, poor concentration or weakness R. Rosenson 2013 Up To Date: Statins: Actions, side effects, and administration
35 Statins Third Report of the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III, or ATP III) from the National Cholesterol Education Program (NCEP) Statin therapy for LDL>100 in secondary stroke prevention SPARCL trial demonstrated nearly a 16% reduction in recurrent stroke with high dose atorvastatin JUPITER trial showed a 48% reduction in the rate of fatal and nonfatal stroke with rouvastatin Stroke 2009: 40: N Engl J Med 2008;359:
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