ABCs of CVA Meds Final 2016 - Baptist Health of CVA Meds...HMG-CoA-Reductase (Statins) Blood ... SBP

October20,2016

ABCs of CVA Meds HyeJinSon,PharmD,BCPS

Chisholm-Burnset.al.Pharmacotherapy:PrinciplesandPractice3rdedition.2013

OriginofStroke


GoldenHourofStroke

• “Time is brain” • Stroke scales • Diagnostic studies

• Neuroimaging • Glucose • PT/INR • BMP/CBC • ECG/Cardiac biomarkers • O2 saturation

• Differential diagnosis • Hypoglycemia • Seizures • Intoxication • Complicated migraine • CNS tumor • CNS infection

Jauchetal.EarlyManagementofAcuteIschemicStroke.Stroke.2013;44:870-947


Initial Care Acute Intervention

Secondary Prevention

Respiratory Support

TPA BP Lowering

Aspirin Antiplatelets

Hemodynamic Support Interventional

Radiology

Anticoagulants for Afib • Warfarin• Novel Anticoagulants

HMG-CoA-Reductase (Statins)

BloodPressureinAcuteIschemicStroke(AIS)

• Hypertension predominates AIS • Goal BP dependent on intervention • If TPA à BP < 180/105 for first 24 hours • If no TPA à SBP < 220 or DBP < 120

• Hypotension suggests alternative cause • Arrhythmia • Cardiac Ischemia • Aortic dissection • Shock/Sepsis


BloodPressureinAcuteIschemicStroke(AIS)

AcuteHypertensionTreatment

Drug Mechanism Dose(IV) Onset Duration

Labetalol Alpha/BetaBlocker10-20mg2-8mg/mininfusion

2-5min 2-6hr

Nicardipine CalciumChannelBlocker 5-15mg/hrinfusion 5-10min 2-6hr

Hydralazine Arterialvasodilator 5-20mg 10min 1-4hr

Enalaprilat ACE-Inhibitor 0.625-1.25mgq6hr 15-30min 12-24hr

Nitroprusside Arterial/venousvasodilator 0.5-3mcg/kg/min Seconds 1-2min


Long-termAntihypertensiveTherapy

• The most important intervention • When

• Reasonable after the first 24 hours • Whom

• Initiate for previously untreated patients • Resume for previously treated patients

• Secondary prevention • Goal: SBP <140 and DBP <90 • Lifestyle modification • Thiazide ± ACE Inhibitor Jauchetal.EarlyManagementofAcuteIschemicStroke.Stroke.2013;44:870-947

Kernanetal.StrokePreventioninPatientswithStrokeandTIA.Stroke.2014;45:2160-2236

JAMA2014;311(5):507-520

Antiplatelets

• Aspirin 325 mg x1, then 81-325 mg/day within 24-48 hours

• Do not initiate aspirin within 24 hours of tPA • Secondary Prevention of noncardioembolic stroke or TIA

• Aspirin 75-100 mg once daily • Clopidogrel 75 mg once daily • Aspirin/ER dipyridamole 25 mg/200 mg twice daily • Cilostazol 100 mg twice daily

Kernanetal.StrokePreventioninPatientswithStrokeandTIA.Stroke2014;45:2160-2236Lansbergetal.Antithromboticandthrombolytictherapyforischemicstroke.Chest2012;141:e601S-36S

AnticoagulantsforAtrialFibrillation(Afib)

• Use of CHA2DS2-VASc score • 0: recommend no antithrombotic therapy • 1: recommend antithrombotic therapy with oral anticoagulation or

antiplatelet therapy but preferably oral anticoagulation • ≥2: recommend oral anticoagulation with

• Warfarin • Dabigatrin • Rivaroxaban • Apixaban

Laneetal.Circulation.2012;126:860-865Kernanetal.StrokePreventioninPatientswithStrokeandTIA.Stroke2014;45:2160-2236

Januaryatel.2014AHA/ACC/HRSGuidelineforAtrialFibrillation.JAmCollCardiol.2014;64(21):2246-2280

Anticoagulants–StrokeRiskAssessmentTool

CHADS2 CHA2DS2-VASc

CHF–1point CHF–1point

Hypertension–1point Hypertension–1point

Age≥75year–1point Age≥75year–1point

Diabetes–1point Diabetes–1point

PriorStrokeorTIA–2points PriorStrokeorTIA–2points

Vasculardisease–1point

Age≥65year–1points

Sexcategory(female)–1point

Laneetal.Circulation.2012;126:860-865

Warfarin(Coumadin)

Dabigatran(Pradaxa)

Rivaroxaban(Xarelto) Apixaban(Eliquis)

Edoxaban(Savaysa)

Mechanism VitaminKAntagonist

DirectThrombinInhibitor DirectFactorXaInhibitor

DirectFactorXaInhibitor

DirectFactorXaInhibitor

Comparedtowarfarin

Canuseinpatientswithvalvularafib

Non-inferiorSimilarratesofhemorrhagebutlessICH,moreGIB.IncreasedMI

Non-inferiorSimilarriskofmajorbleedingbutlowerICHandfatalbleeding,moreGIB

SuperiorLessriskofbleedingandmortality

Non-inferiorLowerratesofbleeding

Trial SPAF RE-LY ROCKETAF ARISTOTLE EngageAF-TIMI48

DoseforAfib Variousdosesdaily

150mgtwicedaily 20mgdailywitheveningmeal

5mgtwicedaily 60mgdaily

Renaladjustment

No CrCl30-49:Ifconcomitantdronedaroneorketoconazole75mgtwicedailyCrCl15-30:75mgtwicedailyoravoidCrCl<15:Avoiduse

CrCl15-50ml/min:15mgdailyCrCl<15ml/min:Donotuse

Decreasedoseto2.5mgtwicedailyif≥2ofthefollowing:≥80yearsold;Weight≤60kg;SCr≥1.5

DonotuseifCrClis>95ml/minCrCl15-50ml/min:30mgdailyCrCl<15ml/min:Donotuse

Reversalagent VitaminK Idarucizumab(Praxbind) Indevelopment:Andexanetalfa(PRT064445)–PhaseIIItrialsAripazine(PER977)–PhaseIItrials

Hanleyelal.JThoracDis.2015Feb;7(2):165–171,Stacyetal.CardiolTher2016June;5(1):1-8

Relative risk reductions of various outcomes in patients with nonvalvular atrial fibrillation receiving various antithrombotic regimens as compared with warfarin or its derivatives

Antonio Culebras et al. Neurology 2014;82:716-724

Acenocoum = acenocoumarol ASA = acetylsalicylic acid CI = confidence interval

HemorrhagicStrokePearls

• No pharmacotherapy to directly treat bleeding • Pharmacotherapy is aimed at supportive care

• Anticoagulation reversal • FFP, PCC, etc • Blood pressure/cerebral perfusion pressure • Cerebral edema/Intracranial pressure

• Vasospasm management (Aneurysmal SAH)

Jauchetal.EarlyManagementofAcuteIschemicStroke.Stroke.2013;44:870-947Kernanetal.StrokePreventioninPatientswithStrokeandTIA.Stroke.2014;45:2160-2236

HemorrhagicStrokeBloodPressure

• SBP < 160 • MAP < 110 • CPP = MAP – ICP • CPP > 60 • Short acting medications

• Antihypertensives • Vasopressors


Prevent hematoma expansion

Maintain cerebral perfusion

CholesterolManagement

• Continue statin during the acute period • Secondary prophylaxis

• Statin therapy with intensive lipid-lowering effects (SPARCL study) • Manage according to 2013 ACC/AHA cholesterol guidelines


ASCVD = atherosclerotic cardiovascular disease ACC = American College of Cardiology AHA = American Heart Association

FourStatinBenefitGroups

Individuals: 1. Clinical ASCVD 2. Primary elevations of LDL-C > 190 mg/dL 3. Diabetes aged 40 to 75 yrs with LDL-C 70-189 mg/dL and without clinical ASCVD 4. Without clinical ASCVD or diabetes with LDL-C 70-189 mg/dL and estimated 10-yr ASCVD risk > 7.5%

http://my.americanheart.org/cvriskcalculator

Stone et al. Circulation 2013;00:000–000




• LDL-C reduction 25-62% • “Rule of 6” = Each doubling of daily dose produces an additional 6%

average reduction • Moderately effective at lowering triglycerides • Modestly raise HDL-C

StatinsEfficacy

• Constipation • Abdominal pain • Diarrhea • Dyspepsia • Nausea • LFT increase (< 2%) • Myopathy, including rhabdomyolysis (0- <0.5%)

StatinsAdverseEffects


Post-StrokeSeizures

• Post stroke seizure: <10% • Recurrence: rare to ~6%

• Early vs. late onset • Predictors: hemorrhagic transformation (HT), severity and

cortical location • No primary prophylaxis • Secondary prophylaxis if multiple early seizures or ICH or HT

• Short term/monotherapy with antiepileptic agent

Jauchetal.EarlyManagementofAcuteIschemicStroke.Stroke.2013;44:870-947Belezaetal.Neurologist.2012May;18(3):109-19.

Post-StrokeSeizures

• Recurrent seizures after stroke should be treated in a manner similar to other acute neurological conditions, and antiepileptic agents should be selected by specific patient characteristics.


SeizureTypes

• Generalized • Absence (petit mal) • Myoclonic • Clonic • Tonic-clonic (grand mal) • Atonic


• Focal (Partial) Seizure • Simple • Complex • Secondarily generalized

• Status Epilepticus: prolonged seizure after 5 minutes

StatusEpilepticusTreatment

NeurocritCare2012;17:3-23

• First-linetherapy(Benzodiazepinetherapypreferred)• Lorazepam0.1mg/kgintravenously(max4mg/dose)• Midazolam5–10mgintramuscularly

• Second-linetherapy• Valproate20–40mg/kgintravenously• (Fos)Phenytoin18–20mg/kgintravenously• Phenobarbital20mg/kgintravenously• Levetiracetam1–3gintravenously


Phenytoin (Dilantin)

Carbamazepine (Tegretol)

Levetiracetam (Keppra)

Zonisamide (Zonegran)

Gabapentin (Neurontin)

Lamotrigine (Lamictal)

Mechanism Fast Na channel blocker

Fast Na channel blocker

Unknown Na and Ca channel stabilization

Ca channel stabilization, increase GABA

Fast Na channel blocker

Loading Dose 10-20mg/kg None Not routine (1000-2000 mg)

None N/A None

Maintenance Dose

4-7mg/kg/day 10-20 mg/kg/day divided TID-QID BID if XR

1000-3000 mg/day

100-600 mg/day 900-3,600mg/day tid-qid

150-800 mg/day divided BID-TID

Therapeutic Range

Total: 10-20 mcg/ml Free: 1-2 mcg/ml

4-12mcg/ml N/A N/A N/A N/A

Centration Dependent Adverse Effects

Ataxia, diplopia, sedation, nystagmus

Diplopia, nausea, dizziness

Sedation, anxiety, irritability

Dizziness, sedation

Sedation Diplopia, dizziness, headaches

Idiosyncratic Adverse Effects

Anemia, gingival hyperplasia, hirsutism, rash

Leukopenia, rash, hyponatremia

Kidney stones, metabolic acidosis, weight loss

Peripheral edema, weigh gain

Rash. May progress to Stevens-Johnson Reaction

Notes Highly protein bound. Maximal infusion rate of 50 mg/minute. Non-linear.

Autoinduction. Genetic variability

No DDI with other seizure medications. Renal dose adjustment

Renal dose adjustment necessary

Start low and titrate slowly due to risk of rash. Valproic acid decreases metabolism (lower)

Zelano.Theradvneuroldisor.2016Sep;9(5):424–435.

Thank you!

http://www.stroke.org/understand-stroke/recognizing-stroke/act-fast

ABCs of CVA Meds Final 2016 - Baptist Health of CVA Meds...HMG-CoA-Reductase (Statins) Blood ... SBP

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