Harold P. Adams, Jr. M.D. Division of Cerebrovascular Diseases Department of Neurology UIHC Comprehensive Stroke Center University of Iowa

Transcription

1 Harld P. Adams, Jr. M.D. Divisin f Cerebrvascular Diseases Department f Neurlgy UIHC Cmprehensive Strke Center University f Iwa

2 I adjudicate events in clinical trials spnsred by Merck and I serve n the DSMB fr a clinical study funded by Medtrnic. I am a cnsultant t Pierre Fabre (France) I receive grant supprt frm NINDS and St Jude Medical I will discuss therapies fr treatment f strke that are nt apprved by the FDA

3 Advances in the diagnsis, preventin and treatment f strke cntinue t ccur Resulting in changes in patient These changes are reflected in natinal guidelines These changes als are generating questins by clinicians Time t address sme f these questins Try t answer 7 f these questin

4 What shuld ur bld pressure targets be nw in the management f patients with acute ischemic r hemrrhagic strke?

5 Arterial hypertensin is cmmnly detected in the setting f an acute ischemic r hemrrhagic strke Arterial hypertensin is a premier risk factr fr premature athersclersis and bth ischemic and hemrrhagic strke An elevated bld pressure may be a cnsequence f the strke Stress f the acute event (headache, agitatin, nausea, vmiting, white cats, etc.) Cmpensatry measure t maintain cerebral bld flw in setting f ischemia r increased intracranial pressure

6 Adverse impact f hypertensin Ptentiate bleeding r recurrent rupture f aneurysm Hemrrhagic transfrmatin f infarctin Ptential adverse effects f rapid lwering f bld pressure Lss f autregulatin leads t pressure-dependent bld flw Lwering bld pressure may wrsen ischemia distal t an arterial cclusin Lwering bld pressure may wrsen ischemia in a patient with increased intracranial pressure

7 Spntaneus decline in bld pressure during first 24 hurs Erratic respnses t medicatins Uncertainties in medical management Level f bld pressure that mandates treatment Desired decline in bld pressure Selectin f acutely administered medicatins Transitining t lnger term care with restarting r adjusting antihypertensive medicatins Clinical trials have given incnclusive results

8 Randmized trial 4071 patients N thrmblysis and treated < 48 hurs Gal f reducing bld pressure 10% - 25% in 24 hurs and gal f < 140/90 mm Hg Outcmes at 14 days/discharge and 3 mnths Death/disability (mrs > 3) Did lwer bld pressures 24 hurs Treatment: mean systlic pressure reduced 12.7% Cntrl: mean systlic pressure reduced 7.2% Outcmes N significant differences between grups He et al, JAMA; 2013 (nline)

9 If systlic BP >200 mm Hg r MAP > 150 mm Hg Aggressive lwering with cntinuus IV infusin and measurements f bld pressure every 5 minutes If systlic BP > 180 mm Hg r MAP > 130 mm Hg and there is cncern abut increased ICP Mnitr ICP and reducing BP carefully with intermittent r cntinuus IV infusin maintain CPP > 60 mm Hg If systlic BP > 180 mm Hg r MAP > 130 mm Hg and there is n evidence f increased ICP Mdest reductin f bld pressure t MAP 110 Hg r target value f 160/90 intermittent/cntinuus meds Mrgenstern et al, Strke; 2010; 41: 2108

10 Intravenus administratin f Labetall Blus: 5-20 mg every 15 minutes Infusin: 2mg/min (maximum 300 mg/day) Hydralazine Blus:5 20 mg every 30 minutes Infusin: µg/kg/minute Nicardipine Infusin: 5 15 mg/hur Indicatins Mean arterial pressure> 120 mm Hg Systlic bld pressure > 160 mm Hg Diastlic bld pressure > 100 mm Hg Maintain cerebral perfusin pressure > 60 mm Hg

11 Bld pressure < 185 mm Hg systlic AND 110 mm Hg diastlic t administer rtpa Aggressive treatment t achieve bld pressure Keep belw these levels after treatment In ther circumstances, gal is t lwer bld pressure by apprximately 15% in first 24 hurs N slid data, general cnsensus Treat if bld pressure > 220 mm Hg systlic r 120 mm Hg diastlic Jauch et al, Strke, 2013

12 Shrt acting medicatins given intravenusly Can be stpped if bld pressure drps t much r if the patient wrsens neurlgically Chices Labetall mg ver 1 2 min, repeat x 1 Nicardipine 5 mg/hr infusin, may increase by 2.5 mg/hr q 5 15 min, maximum 15 mg/hr Requires cntinuus bld pressure mnitring Can try hydralazine, enalaprilat, sdium nitrprusside If sdium nitrprusside is required, patient generally can nt receive tpa Jauch et al, Strke, 2013

13 What is the upper time limit fr treatment with rtpa t be effective? What is the upper age limit fr thrmblytic therapy

14 Favrable utcmes rt-pa Cntrl Odds Rati p-value Treated < 6 hr 1609/ / ( ) p =0.001 Treated < 3 hr 365/ / ( ) p < Treated 3 6 hr 1180/ / ( ) p = 0.23 Wardlaw et al, Lancet, 2012

15 Pled analyses f clinical trials Time Odds f Favrable Outcmes < 90 minutes 2.55 ( ) minutes 1.64 ( ) minutes 1.34 ( ) minutes 1.22 ( ) Lees et al, Lancet, 2010; 375: 1695

16 Eurpean trial demnstrated efficacy ut t 4.5 hurs time perid included in current guidelines Nt as effective as earlier treatment Nt likely t expand time windw much mre Are sme differences in selectin criteria frm treatment < 3 hurs Exclusins fr hurs Age > 80 Histry f diabetes and prir (clinical) strke NIH Strke Scale scre > 25 Use f ral anticagulants regardless f INR

17 N age restrictin fr treatment f persns < 3 hurs Children Elderly Age restrictin fr treatment f persns hurs D nt treat persns lder than 80

18 D cartid Dpplers add anything if we have the results f a MRA f the head/neck?

19 CTA Extracranial/intracranial vessels at time f CT Invlves IV cntrast cntrast nephrtxicity Availability f 3-D recnstructin f images MRA Extracranial/intracranial vessels at time f MRI Invlves IV cntrast cntraindicated in renal failure Pacemaker, claustrphbia, metal May ver-estimate degree f arterial narrwing Cartid duplex (Dppler) Visualizes cartid bifurcatin nly Prvides infrmatin abut the arterial wall Subject t perfrmance variability

20 MRA and CTA are mre expensive that cartid duplex Advantage f imaging bth intracranial and extracranial vasculature D nt image smaller intracranial vessels Detect aneurysms, vascular malfrmatins Sme surgens want cnfirmatin abut the nature f the arterial lesin befre deciding abut cartid endarterectmy Generally, a cartid duplex is nt needed if cartid endarterectmy is nt planned

21 Is transthracic echcardigraphy sufficient t lk fr clt?

22 Accunts fr apprximately 20% - 25% f ischemic strkes Occurs in persns f all ages regardless f sex r ethnicity Causes vary by age Cngenital heart disease in children Athersclertic heart disease in lder persns Sme patients may nt have vert cardiac symptms r signs

23 Nn-invasive Limited sensitivity Large chest r bese Images left ventricle wall, chamber Ventricular aneurysm Ventricular akinesia Intraventricular thrmbus r mass Als may detect atrial myxma, PFO, valvular lesins

24 Minimally invasive Esphageal disease Risk f bleeding r aspiratin Requires sedatin and analgesia Images Left atrium and appendage Valves Arta Mre sensitive than TTE Detects lesins f uncertain significance

25 Enlargement f left atrium r appendage Thrmbus in left atrium r appendage Inter-atrial septal lesins Atrial turbulence ( smke ) Valvular lesins Vegetatin Lambl excresence Calcificatin Valvular strands Athersclertic disease f the arta

26 Intravenusly administer agitated saline Assess mvement f bubbles Right and left sides f the heart Early appearance n the left side Right-t-left shunt Fund with Atrial r ventricular septal defect Patent framen vale Pulmnary arterivenus malfrmatin

27 Cardiac imaging remains imprtant in evaluatin f patients with ischemic strke Can be avided if ther cause established Cardigenic emblism usually arises frm lesins in the left atrium, left atrial appendage, mitral valve Indicatins fr TTE Presumed left ventricular rigin Anterir wall MI, ventricular aneurysm Indicatins fr TEE T search mst ther pssible cardiac causes f strke

28 What is the rle f statins in management f acute strke?

29 Increasing evidence that hyperlipidemia is a risk factr fr ischemic strke Prmtes large artery athersclersis and small vessel brain disease Als indirectly leads t strke via cardiemblism in patients with crnary artery disease Measuring levels f chlesterl in a patient with strke is a quality measure Nw dne in virtually all patients with ischemic strke

30 Inhibit HMG-CA reductase, the rate-limiting enzyme f the mevalnate pathway fr chlesterl synthesis Als increased clearance f LDL lipprtein frm the bld Mdest increase in HDL chlesterl levels Reduce triglycerides by 20% - 40% Majrity f chlesterl synthesis is at night ratinale fr giving medicatin in the evening Imprve endthelial functin and maintain plaque stability Mdulate inflammatry respnses Prevent frmatin f thrmbi

31 Atrvastatin Placeb p-value (80 mg/d) N = 2365 N= 2366 Fatal r nnfatal strke % % 0.05 TIA % % Crnary event % % Death % % 0.77 ICH SPARCL, N Engl J Med, 2006; 355: 549

32 Mst pwerful medicatins t lwer LDL chlesterl First chice fr treatment f mst patients with ischemic strke Chice f medicatin Rsuvastatin, atrvastatin, and simvastatin have the greatest impact n lwering LDL chlesterl Atrvastatin and fluvastatin d nt require dse adjustment in patients with renal disease Lwer dses f pravastatin r rsuvastatin in patients with liver disease Pravastatin and fluvastatin are the least likely t cause muscle txicity

33 May be sme increase in risk f hemrrhagic strke with aggressive lwering f LDL chlesterl May wish t avid medicatins in this situatin Muscle disease Relatively uncmmn with treatment with statin alne Myalgias: 2% - 11%, mysitis: 0.5%, myglbinuria: 0.1% Usually begins within the first weeks f treatment Mnitred by CK levels Variatin f SLCO1B1 gene, which is invlved in the absrptin f statins, increases risk Increased risk if renal dysfunctin Increased risk with medicatins that blck CYP3A4

34 Is there a rle fr SSRIs in acute strke?

35 Apprximately 75% persns with strke survive and need sme rehabilitatin (400,000 annually) Measures t maximize recvery culd be prescribed t large numbers f patients N medical treatment has been established as effective given as an adjunct t current rehabilitatin Ptential fr a much larger impact n the public s health than time-limited acute treatments

36 Changes in metablic activity in bth the ipsilateral and cntralateral cerebral hemispheres First hurs and days Changes in CBF and CMRO2 Edema, diaschisis, inflammatin First days and weeks Cellular grwth and excitability Structural and physilgical changes First weeks and mnths Treatment and experience effects Cramer, Strke, 2004; 36: 2695

37 Cmmn cnsequence f strke Assciated with impaired recvery Mtr perfrmance Cgnitive recvery Activities f daily living Assciated with increased mrtality Effects persist event when adjusting fr age, severity f impairments, and cmrbid illnesses

38 SSRI increase expressin f VEGF in the dentate gyrus f the hippcampus in experimental mdels The effects f SSRI may be augmented because f increases in VEGF SSRI may imprve bth mtr and sensry deficits after strke Thus, SSRI may be superir t ther classes f antidepressants t imprve utcmes after strke Gallard and Mir, Lancet Neurlgy, 2011; 10: 499

39 Randmized trial in 8 French centers testing fluxetine 20 mg/day fr 3 mnths in additin t rehabilitatin Fluxetine 57 subjects, placeb 56 subjects Outcmes assessed at 3 mnths by Fugl-Myer and mrs scres Fluxetine Placeb P-value Fugl-Myer / / FM Imprve / / mrs (26%) 5 (9%) Chllet et al, Lancet Neurlgy, 2011; 10: 123

40 Have tried t answer sme f the mre cmmn questins abut strke care The management f hypertensin in the setting f acute strke remains unsettled Still, recmmendatins abut situatins t lwer BP Cautin shuld be exercised in lwering the BP The time windw fr treatment with intravenus thrmblysis has expanded t 4.5 hurs Generally the same criteria as fr treatment < 3 hurs D nt treat persns lder than 80 in perid f hurs

41 Examinatin f the vasculature and heart remain imprtant cmpnents f the assessment fr the cause f ischemic strke Cartid duplex ultrasngraphy is an ptin but its limitatins shuld be recgnized In general, TEE prvides mre infrmatin abut the cause f strke than des TTE TTE des have sme rle in evaluatin Treatment f hyperlipidemia is an imprtant part f lng-term care f persns with ischemic strke The use f SSRI may help augment recvery after strke