Dawn Matherne Meyer PhD,RN,FNP-C Assistant Professor University of California San Diego Evidence Based Care of the Stroke Patient: A Focus on Acute Treatment, BP Management, & Antiplatelets TIME IS BRAIN Dawn M Meyer RN, FNP-C,PhD
OBJECTIVES 1. Neuro-anatomy and function 2. Updated rt-pa prescribing 3. Evidence based blood pressure management 4. Evidence based antiplatelet use Dawn M Meyer RN, FNP-C,PhD
HTTP://WWW.YOUTUBE.COM/WATCH?V=_JIH8HKH9-M
Functional Neuroanatomy
Functional Anatomy of Brain
Sensory Pathways
Motor Pathways
Vascular Neuroanatomy
Circle of Willis- Blood Supply of the Brain Dawn M Meyer RN, FNP-C,PhD
Dawn M Meyer RN, FNP-C,PhD
Dawn M Meyer RN, FNP-C,PhD
TREATMENT OF ISCHEMIC STROKE Dawn M Meyer RN, FNP-C,PhD
t-pa (Activase ) THROMBOLYTIC THERAPY t-pa is the ONLY FDA approved treatment for ischemic stroke (based on the NINDS trial). Nationally 2-3% of ischemic stroke patients receive TPA. Some reasons that patients do not receive t-pa: Arrive at hospital too late Inability for hospitals to triage pts Concerns about bleeding complications Dawn M Meyer RN, FNP-C,PhD
NINDS t-pa STROKE TRIAL Randomized, double blind, placebo-controlled trial Treatment with 0.9mg/kg t-pa (Activase ) vs placebo within 3 hours of stroke symptom onset 624 patients treated within 3 hours 32% more t-pa patients had minimal or no disability at 90 days 6.4% of patients had a symptomatic intracranial hemorrhage by 36 hours after treatment Mortality at 90 days was 17% in t-pa group and 21% in placebo group (The NINDS Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. NEJM, 1995) Dawn M Meyer RN, FNP-C,PhD
CAUTIONS WITH t-pa THROMBOLYTIC THERAPY The t-pa for stroke and MI are DIFFERENT. Double check to ensure you are administering Activase (alteplase) for ischemic stroke. A CT scan must be performed before administering Activase (alteplase). Major complication of t-pa: 6.4% symptomatic intracranial hemorrhage (ICH) Dawn M Meyer RN, FNP-C,PhD
ADMINISTERING t-pa DOSING: 0.9 mg/kg * pt weight in kg= TOTAL DOSE 10% as IV Bolus over 1 minute Remaining 90% 1 hr IV infusion MAX DOSE= 90mg MONITORING: Vital signs and neuro checks every 15 minutes x2 hours from time of t-pa, every 30 minutes x6 hours, every 1 hour x 16 hours, then per unit protocol. Dawn M Meyer RN, FNP-C,PhD
CARE OF THE ISCHEMIC STROKE PATIENT Dawn M Meyer RN, FNP-C,PhD
COMMON MEDICATIONS ORDERED FOR THE ISCHEMIC STROKE PATIENT Anti-platelets or anticoagulants Blood pressure management DVT prophylaxis Lipid lowering medications Smoking Cessation Dawn M Meyer RN, FNP-C,PhD
Blood Pressure Management Emergency Department Goal BP for patients treated with rt-pa is SBP <185 and DBP <110 Goal for ischemic stroke patients not treated with rt-pa is SBP <220 and DBP <120 Dawn M Meyer RN, FNP-C,PhD
Blood Pressure Management ICU/Stroke Unit rt-pa treated Patients Goal SBP <185 and DBP <110 (or MAP 90-110) for 1 st 24 hours After 24 hours, the BP goal should be 120/80* The MAP should not be decreased more than 15% per day * Patients with hemodynamically significant stenosis of the large arteries (e.g. internal carotid arteries) should not have the BP lowered without further workup. Dawn M Meyer RN, FNP-C,PhD
Blood Pressure Management ICU/Stroke Unit Non-rt-PA treated Patients Goal SBP <220 and DBP <120 (or MAP <130) for 1 st 24 hours After 24 hours, the BP goal should be 120/80* The MAP should not be decreased more than 15% per day * Patients with hemodynamically significant stenosis of the large arteries (e.g. internal carotid arteries) should not have the BP lowered without further workup. Dawn M Meyer RN, FNP-C,PhD
Nitroglycerin
Labetolol
Dawn M Meyer RN, FNP-C,PhD Enalaprilat
Hydralazine
Nitroprusside
Clevidipine
Nicardipine
Current Antiplatelet Therapy in Stroke Aspirin Clopidogrel Aspirin + ER Dipyradamole
Aspirin Aspirin Mechanism: (inhibits PG synthesis) - Inhibits arachidonic acid metabolism necessary for thromboxane production - Covalently acetylates Cyclooxygenase (irr.) - Inhibits platelet function within 1 hour - Lasts entire platelet lifetime (~10d) Efficacy & Dosage: - Efficacy is not in question - Ideal dosage still debated
Aspirin-Efficacy CAST& IST- SALT- UK-TIA- Metaanalysis ~40,000 pts. Reduction of 7/1000 ischemic stroke (CVA+all death) ASA 75mg 18.0% RRR (major cva/ MI/ vascular death) ASA 300 vs 1200mg = effective. 15% OR (-3 29%) DUTCH-TIA- (CVA/MI/vasc. death) ASA 30 vs. 283mg both effective. 0.91 Hazards Ratio
ASA Meta-analyses: APTC (1994): 46 ASA trials 25% OR (cva/mi/vasc.death) Algre & van Gijn (1996): 10 trials. 6,171 pts. 16% OR (cva/mi/vasc.death) 13% Relative RR (CI=4-21%) Same for any dose ASA (50-1500mg/d) Johnson et al. (1999): 11 trials. 5,228 pts. 15% Relative RR for cva (CI=6-23%) Same for any dose ASA (50-1500mg/d) ~15-18% RRR for Stroke, NNT 100 APTC 1994. Algre & van Gijn 1996. Johnson et al. 1999. Aspirin
Clopidogrel Thienopyridine derivative: Same chemical family as Ticlopidine. Inhibits ADP induced plt aggregation. Pharmacodynamics are similar to ASA. 400mg x 1 => max 40% inhibition. 50-100mg QD => 50-60% inhibition may take 4-7 days for max effect. Patrono et al. Chest. 1998; 114:470-488
Clopidogrel CAPRIE: (Clopidogrel vs ASA) Clopidogrel(75mg) ASA(325mg) 19,185 pts c h/o CVA/ MI/ PVD Incidence 5.83% (ASA) 5.32% (Clopidogrel) 8.7% (p=0.043) RRR overall, 7 stroke (p=0.26) CAPRIE. Lancet. 1996;378:1329-1339. NNT 60
Dipyridamole Pyrimidopyrimidine derivative: Vasodilator & antiplatelet properties. Mechanism: Inhibits Phosphodiesterase increased c-gmp Result is platelet inhibition. *Blocks Adenosine uptake into cell increased intra- plt c-amp Result is platelet inhibition. Patrono et al. Chest. 1998; 114:470-488
ASA+ERDP ESPS-2: (E.R.Dipyridamole 200mg bid vs. ASA 25mg bid) 6,602 pts with prior stroke/tia 4 treatment groups (including placebo) RRR (for cva) vs Placebo Low ASA ERDP ASA+ERDP 18.0% (p=0.013) 16.3% (p=0.039) 37.0% (p<0.001) Diener et al. ESPS-2. J. Neuro Sci. 1996l143:1-13. NNT 18 (placebo)/34 (ASA)
ASA+ERDP ESPRIT/ESPRIT-2 Trial ASA+ERDP (n=1363) ASA (n=1376) Primary outcome (death from all vascular causes, nonfatal stroke, non-fatal MI, or major bleeding complication) 173 (13%) ASA+ERDP 216 (16%) ASA alone HR 0.80; ARR 1.0% per year 24% RRR when compared to OAC (INR 2-3)
ASA+Clopidogrel +
ASA+Clopidogrel MATCH: (Clopidogrel+ASA) vs. Clopidogrel Clopidogrel(75mg)+ASA(75mg) vs Clopidogrel(75mg) 7,599 high risk pts (CVA/TIA + 1 Risk Factor) 18 month follow up Results: Event Rate = 15.7% vs. 16.7% RRR 6.4% (p=0.244) **nss Hemorrhage Rate = 2.6% vs. 1.3% RRE 100% (p=0.029) **ss Diener et al. MATCH. Lancet.2004;364:331-337
PRoFESS VERSUS with OR without
Primary Outcome First Recurrence of stroke, ITT Analysis Total number of recurrent strokes was 1,814 ASA+ERDP n=916 (9.0%) Clopidogrel n=898 (8.8%) HR 1.01, CI 0.92-1.11 Because CI extends beyond 1.075 did not meet the pre-specified non-inferiority endpoint 87.4% of recurrent strokes were ischemic There was no significant difference in 3 month mrs 3 between the groups (4.1% ASA+ERDP, 3.9% clopidogrel) Per protocol analysis recurrence rate was 7.6% ASA+ERDP, 7.7% clopidogrel
Effect on Clinical Practice ASA+ERDP is not inferior to clopidogrel Patient selection is key to choice of antiplatelet for secondary stroke prevention ASA financial barriers ASA+ERDP Ischemic stroke, no significant cardiac history, CHF* Clopidogrel Cardiac history, PAD, risk for ICH, migrainours, hx GI bleed
When We Combine Things We Don t Always Get What We Expect
Summary Understanding neuro-anatomy and function allows you to anticipate the needs of your patient and understand their neurologic deficit rt-pa is the only FDA approved treatment for ischemic stroke Blood pressure management is vital to maintaining cerebral perfusion after stroke while minimizing the risk of hemorrhagic transformation or expansion The choice of antiplatelet therapy is guided by the patient profile Dawn M Meyer RN, FNP-C,PhD
Dawn M Meyer RN, FNP-C,PhD THE END