Disclosures: Maximo C. Kiok, M.D. Medical Director of Stroke Program Trinity Health System Therapy Options for Acute Ischemic Stroke Trinity Stroke Nursing Symposium Feb 18, 2012 By Maximo C. Kiok, M.D. Overview of Treatment Options IV thrombolytic therapy (0-3 hrs) IV thrombolytic therapy (3-4.5 hrs) IA thrombolytic therapy Endovascular mechanical thrombectomy (Merci, Penumbra, Solitaire, etc.) • Balloon angioplasty with stenting • Anti-platelet agents for non-thrombolytic Rx • Anticoagulants for atrial fibrillation • • • • IV Thrombolytic Therapy • NINDS Stroke Trial (1995): 0-3 hrs window. – Benefit at 90 days – Risk of symptomatic cerebral hemorrhage within first 36 hours – Mortality Rate at 90 days – Exclusion criteria for administration of I.V. t-PA References: • Adams H P Jr, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups. Stroke 2007; 38:1655-1711. • The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995; 333: 1581–1587. The trial had two parts. Part 1 (in which 291 patients were enrolled) tested whether t-PA had clinical activity, as indicated by an improvement of 4 points over base-line values in the score of the National Institutes of Health stroke scale (NIHSS) or the resolution of the neurologic deficit within 24 hours of the onset of stroke. No benefit found for IV t-PA. Part 2 (in which 333 patients were enrolled) used a global test statistic to assess clinical outcome at three months, according to scores on the Barthel index, modified Rankin scale, Glasgow outcome scale, and NIHSS. Benefit found! BENEFIT of IV t-PA Treatment at 0-3 Hours As compared with patients given placebo, patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at three months on the assessment scales. Risk of Symptomatic Intracerebral Hemorrhage (sICH) within 36 hours after the onset of stroke I.V. t-PA 6.4% Placebo 0.6% Mortality Rate at 3 Months After Onset of Stroke I.V. t-PA 17% Placebo 21% Exclusion criteria Historical • Any past medical history of intracranial hemorrhage • Stroke or head trauma in the previous 3 months • Myocardial infarction in the previous 3 months • Gastrointestinal or urinary tract bleeding in the previous 21 days • Major surgery in the previous 14 days • Arterial puncture at a noncompressible site in the previous 7 days • The use of dabigatran within 48 hours prior to stroke onset is a relative contraindication Exclusion criteria Clinical • Symptoms of stroke suggestive of subarachnoid hemorrhage (such as severe headaches and nausea, vomiting, photophobia, nuchal rigidity or obtundation). • Caution should be exercised in treating a patient with major deficits (NIHSS >22). • Seizure at the onset of stroke is an exclusion if the residual impairments are due to postictal phenomenon; seizure is not an exclusion if the clinician is convinced that residual impairments are due to stroke and not to postictal phenomenon • Spontaneously clearing stroke symptoms • Only minor and isolated neurologic signs (NIHSS <4) • Persistent blood pressure elevation (systolic ≥185 mmHg, diastolic ≥110 mmHg) • Active bleeding or acute trauma (fracture) on examination Exclusion criteria Laboratory • Platelets <100,000/mm3* • International normalized ratio (INR) >1.7 if on warfarin*; the use of dabigatran within 48 hours of stroke onset is a relative contraindication • Serum glucose <50 mg/dL (<2.7 mmol/L) • Elevated partial thromboplastin time (aPTT) if on heparin* Exclusion criteria Head CT scan • Evidence of hemorrhage • Evidence of a multilobar infarction with hypodensity involving >33 percent of the cerebral hemisphere PATIENT'S NAME DATE & TIME OF ONSET CATEGORY YES NO tPA EXCLUSION CRITERIA Onset > 3 Hours Onset > 3 hours Age < 18 years Age < 18 years History of Present Seizure Illness Subarachnoid Hemorrhage Head Trauma Pregnancy <=48 hours <= 7 days Past Medical History ___________________________________ ___/___/____ ____:____:____ <=14 days <= 21 days <= 3 months Any time in the past Seizure at onset of stroke symptoms. Subarachnoid hemorrhage (severe HA, nausea/vomiting, neck stiffness, anisocoria, obtundation, retinal hemorrhage, high BP) Serious head trauma at onset of stroke. Pregnant Heparin/Enoxaparin within the last 48 hours and has elevated PTT. Arterial puncture at noncompressible site within the last 7 days. Major surgery within the last 14 days. Hemorrhage in gastrointestinal or urinary tract within the last 21 days. Recent stroke or serious head trauma within the past 3 months. Intracranial hemorrhage Large middle cerebral artery (MCA) territory infarction (sulcal effacement or blurring of graywhite junction in greater than 1/3 of MCA territory), or shows hemorrhage or tumor. PT is >15 seconds (or INR > 1.7) PTT is elevated and patient had been on heparin in the past 48 hours. Platelet count is <100,000/uL. Glucose <50 mg/dL or >400 mg/dL. Troponin-I elevated Pregnancy Test (if female in child-bearing age) is positive. ST-elevation or T-inversion Systolic blood pressure >185 mmHg. Diastolic blood pressure >110 mmHg. NIH Stroke Scale score >22. Symptoms rapidly improving. NIHSS < 4 CT BRAIN LABS EKG BP Neuro Exam Note: If any of above criteria has "Yes", then patient is excluded from receiving IV t-pa. Signed: Name of Physician ________________________________ ________________________________ IV Thrombolytic Therapy • European Cooperative Acute Stroke Study III (ECASS-III) 2008: 3-4.5 hrs window. – Benefit at 90 days – Risk of symptomatic cerebral hemorrhage within first 36 hours – Mortality Rate at 90 days – Additional exclusion criteria for administration of I.V. tPA References: • Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; 359:1317 (ECASS-III) • Del Zoppo GJ, Saver JL, Jauch EC, et al. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator. A science advisory from the American Heart Association/American Stroke Association. Stroke 2009; 40:2945. BENEFIT of IV t-PA Treatment at 3-4.5 Hours As compared with patients given placebo, patients treated with t-PA were 16 percent more likely to have minimal or no disability at three months on the assessment scales. Absolute improvement of 7.2% only. In the alteplase group, 52.4% had a favorable outcome (defined as a score of 0 or 1 on the modified Rankin scale), compared to the placebo group (45.2%), representing an absolute improvement of 7.2 percentage points (odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; relative risk, 1.16; 95% CI, 1.01 to 1.34; P=0.04). Risk of Symptomatic Intracerebral Hemorrhage (sICH) within 36 hours after the onset of stroke I.V. t-PA 2.4% Placebo 0.3% There were more cases of intracranial hemorrhage in the alteplase group than in the placebo group (27.0% vs. 17.6%, P=0.001). Definition of Symptomatic Intracranial Hemorrhage In the ECASS III protocol, symptomatic intracranial hemorrhage was defined as: 1. Any extravascular blood in the brain or within the cranium 2. Identified as the cause of any neurologic deterioration, and 3. With a magnitude of a. 4 points or more in the NIHSS, or b. That led to death. Mortality Rate at 3 Months After Onset of Stroke I.V. t-PA 7.7% Placebo 8.4% Additional exclusion criteria for 3-4.5 hour use of IV tPA Historical • Age >80 years • History of both diabetes and previous stroke • Current use of any anticoagulant (e.g. warfarin, enoxaparin) Clinical • NIHSS >25 Intravenous Administration of tPA • Infuse 0.9 mg/kg (maximum dose 90 mg) over 60 minutes with 10% of the dose given as a bolus over 1 minute. • Admit the patient to an intensive care or stroke unit for monitoring. • Perform neurological assessments every 15 minutes during the infusion and every 30 minutes thereafter for the next 6 hours, then hourly until 24 hours after treatment. • Measure blood pressure every 15 minutes for the first 2 hours and subsequently every 30 minutes for the next 6 hours, then hourly until 24 hours after treatment. • Increase the frequency of blood pressure measurements if a systolic blood pressure is ≥180 mm Hg or if a diastolic blood pressure is ≥105 mm Hg; administer antihypertensive medications to maintain blood pressure at or below these levels . • If the patient develops severe headache, acute hypertension, nausea, or vomiting, discontinue the infusion (if rtPA is being administered) and obtain emergency CT scan. • Delay placement of nasogastric tubes, indwelling bladder catheters, or intra-arterial pressure catheters. • Obtain a follow-up CT scan at 24 h before starting anticoagulants or antiplatelet agents. . del Zoppo G J et al. Stroke 1998;29:4-11 Copyright © American Heart Association Thank you!