Stroke Treatment and Prevention 2016

Transcription

1 9:45 10:45 am Transient Ischemic Attacks: Rapid Evaluation and Treatment SPEAKER Seemant Chaturvedi, MD Presenter Disclosure Information The following relationships exist related to this presentation: Seemant Chaturvedi, MD: Contracted Research for Boehringer Ingelheim Pharmaceuticals, Inc. Off-Label/Investigational Discussion In accordance with pmicme policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations. Topics for discussion Stroke Treatment and Prevention 2016 Seemant Chaturvedi MD, FAHA, FAAN Professor of Neurology University of Miami Miller School of Medicine Revised definition of TIA Goals of the TIA/stroke evaluation Dual antiplatelet therapy for TIA/minor stroke Cardiac sources of embolism Large vessel atherosclerosis Strokes of undetermined cause Importance of multi-modality therapy Stroke Incidence and Cost in United States 795,000 cases annually -70% first strokes # 4 cause of death $ 55 billion annual health cost 4 million stroke survivors at risk for recurrence Patient vignette 60 year old man with three episodes of slurred speech, ataxia Longest episode lasted 15 minutes Hx of smoking, hyperlipidemia No hx of stroke or MI Not taking medications at the time of hospitalization Most strokes can be prevented

2 New definition of TIA TIA is a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction It is reasonable to hospitalize patients with TIA if it occurred in the last 72 hours, esp. if ABCD score is 3 Acute Care for Stroke Patients Goals of the Work-Up Differential diagnosis Rule out conditions mimicking stroke Ischemic versus hemorrhagic stroke Assess eligibility for thrombolysis or other acute interventions Determine location and etiology of stroke Prevent and treat acute medical and neurologic complications Differential Diagnosis Conditions Mimicking Stroke Seizure with postictal paralysis Occult trauma Intracranial mass tumor, subdural hematoma Metabolic disorder hypoglycemia Migraine Psychological or somatoform disorder NIH Stroke Scale Consciousness 0-3 Orientation 0-2 Commands 0-2 Gaze 0-2 Visual fields 0-3 Facial paresis 0-3 Arm motor (x2) 0-4 Leg motor (x2)0-4 Limb ataxia 0-2 Sensory 0-2 Language 0-3 Dysarthria 0-2 Inattention 0-2 Goals of Therapy Stabilize patient/reverse stroke Thrombolysis or other reperfusion if appropriate Prevent recurrent thromboembolism Maintain collateral blood flow Prevent peristroke complications DVT, pneumonia, cerebral edema Initiate strategies for secondary prevention Rehabilitate patient and restore neurologic function NIH Stroke Scale (NIHSS). Available at Accessed March 15, 2007.

3 Urgency of treatment with IV tpa Time frame 0-90 mins mins mins 15 Lancet 2010; 375: NNT for excellent outcome Treatment for patients with TIA Antiplatelet therapy Is there a role for anticoagulation? Should we use statins? Should we lower the blood pressure and by how much? When should we consider carotid endarterectomy? What if the work-up is negative? ABCD Score Item Assessed Points Risk Factor Age 1 >/= 60 years Blood Pressure 1 SBP >/= 140 or DBP >/= 90 TIA Score 0-2 Stroke Score - >/= 3 Clinical Features 1 Unilateral weakness with or without speech impairment Clinical Feature 2 Speech impairment without weakness Duration 2 TIA duration >/=60 minutes Duration 1 TIA duration minutes Medical History 1 Diabetes TIA Score: 0-2 TIA Score: >/= 3 CHANCE study Conducted in China 5170 patients with minor stroke or TIA who could be treated within 24 hours Compared aspirin alone to aspirin + clopidogrel Clopidogrel 300 mg load given Patients followed for 90 days 10/30/2013 CHANCE study results Rate of stroke reduced with A+C compared to aspirin alone 8.2% with A+C 11.7% with aspirin alone 32% reduction (p<0.001) No increase in major bleeding or hemorrhagic stroke Questions Should we incorporate the results of the CHANCE study in our practice? There is a NIH-sponsored study in North American also evaluating dual AP therapy vs. aspirin monotherapy for TIA/minor stroke POINT trial

4 ASA recommendations The combination of aspirin and clopidogrel might be considered for initiation within 24 hours and continued for 90 days Class IIb Why is finding atrial fibrillation so important? Anticoagulation: 65-80% RRR for preventing recurrent stroke It is the only (common) stroke mechanism we treat with anticoagulation Role for anticoagulation? Yes, if there is a major risk source of cardiac emboli Atrial fibrillation Artificial valve LV thrombus Cardiomyopathy with severe reduced EF Atrial fibrillation VKA therapy, apixaban, and dabigatran are all indicated for prevention of stroke in patients with nonvalvular AF. Selection of agent should be individualized based on risk factors, cost, patient preference, and other clinical factors such as renal function. Class I Atrial fibrillation Rivaroxaban is reasonable for the prevention of stroke in patients with nonvalvular AF Class IIb Timing of treatment in the setting of AF For most patients with a stroke or TIA in the setting of AF, it is reasonable to initiate oral anticoagulation within 14 days after the onset of neurological symptoms. If high risk for hemorrhagic transformation, it is reasonable to delay anticoagulants beyond 14 days Class IIa

5 Age-Related Trends in AF Management of AF Features of novel oral anticoagulants Unmet Need The risk of stroke in AF increases dramatically with age. However, the use of anticoagulation decreases. Fast onset/offset Dramatically reduce the rate of intracerebral hemorrhage No need for routine lab monitoring No major diet interactions Fixed oral dosing Reversal agent for dabigatran just released Increasing Age Statin therapy Statin therapy with intensive lipid lowering effects is recommended to reduce risk of stroke among patients with stroke or TIA presumed to be of atherosclerotic origin and LDL 100 mg/dl Class I Antihypertensive therapy BP therapy is indicated for previously untreated patients with stroke or TIA, who after the first several days, have an established SBP 140 mm Hg or DBP 90 mm Hg (Class I) Goals for target BP are uncertain <140/90 is reasonable (Class IIa) Large vessel atherosclerosis Intracranial atherosclerosis Extracranial atherosclerosis Importance of Intracranial Stenosis Atherosclerotic intracranial stenosis important cause of stroke especially in Blacks, Hispanics, and Asians 90,000 patients with TIA or Stroke / year in USA Approximately 50,000 strokes per year at a cost of $750,000,000 in 1 year and $4.5 billion over the lifetime of these patients Based on ethnic and racial make-up of world population, may be most important cause of stroke

6 Intracranial stenosis Typically refers to vessels including basilar artery, distal vertebral, middle cerebral artery (MCA), distal carotid Not visualized with carotid duplex Need alternate imaging modalities MRA, CTA, Transcranial doppler, angiography Identical in both arms: Aggressive Medical Management Aspirin 325 mg / day for entire follow-up Clopidogrel 75mg per day for 90 days Aggressive, protocol driven risk factor management primarily targeting systolic blood pressure < 140 mm Hg (130 mm Hg diabetics) and low density cholesterol < 70 mg / dl Intervent USA a lifestyle modification program SAMMPRIS Results: 30 Day Outcome 14.7% (n = 33) of patients treated with PTAS experienced a stroke or died versus 5.8% (n = 13) of patients treated with AMM alone p = Intracranial angioplasty or stenting For patients with 70-99% intracranial stenosis, stenting with the Wingspan stent system is not recommended Class III (shown to be harmful) Usefulness of angioplasty alone is unknown and is considered investigational Class IIb Absolute Benefits of Carotid Endarterectomy (CEA) Factors affecting the risk/benefit ratio Absolute RR Ipsilateral Stroke/Yr Favors medical rx Favors surgery Sex Female Male Lesion Smooth Ulcerated Sx type Retinal Hemispheric Collaterals Present Absent CEA showed only marginal benefits on annual rates of ipsilateral stroke for patients with asymptomatic or moderate lesions. Dramatic benefit was seen for high-grade symptomatic stenoses. Comorbidity Present Absent Chaturvedi S. Emergency Medicine 2000; 32: 46-55

7 How many patients need to be operated on? What about intensive medical therapy? 50-99% stenosis subgroup Number needed to treat (NNT) Men 9 Women 36 Age <65 years 18 Age >75 years 5 < 2 weeks 5 There has never been a completed large multi-center study done to compare carotid revascularization + intensive medical therapy vs. intensive medical therapy alone LDL <70 mg/dl SBP <140 for nondiabetics, <130 for diabetics Similar to SAMMPRIS, except for extracranial stenosis >12 weeks 125 Carotid stenosis 2016 Medical Management Newer antiplatelet agents Aggressive use of statins Targeted BP lowering ACE/ARB utilization Smoking cessation Control of other risk factors (DM) Other lifestyle interventions Carotid disease Carotid endarterectomy (CEA) is associated with better outcomes in symptomatic patients compared to carotid artery stenting (CAS) Especially in patients > age 70 years Especially in patients with symptoms in the past 1-2 weeks What about asymptomatic carotid stenosis Same scenario of 80% internal carotid stenosis Medical therapy, CEA, or carotid stenting? This is being evaluated in an important new trial ASA primary prevention guidelines Patients with asymptomatic carotid stenosis should be prescribed daily aspirin and a statin. Patients should also be screened for other treatable risk factors for stroke. Class I It is reasonable to consider performing CEA in asymptomatic patients who have >70% stenosis of the internal carotid artery if the risk of perioperative stroke, MI, and death is low (<3%). However, its effectiveness compared with contemporary best medical management alone is not well established (Class IIa; Level of Evidence A).

8 Two parallel multi-center randomized, observer blinded endpoint trials NINDS funded clinical trial (U01 NS080168) Notice of award received March 11 th, 2014 Clinical Coordinating Center Mayo Clinic Florida Statistical and Data Coordinating Center University of Alabama at Birmingham About 100,000 carotid REVASC procedures done in the US per year Approximately 80% are done in asymptomatic patients Improvements in medical therapy have raised doubt the value of these procedures What do we mean by asymptomatic No clear-cut TIA or stroke in the territory of the stenosed carotid artery in the past 6 months Patients with vague, nonspecific symptoms such as lightheadedness or dizziness would not qualify as TIA Syncope is not considered a carotid TIA Symptoms of posterior circulation TIA/stroke (brainstem/cerebellum) are considered asymptomatic from the carotid standpoint Primary Aim To assess in patients with 70% asymptomatic stenosis: If contemporary MEDICAL alone is not inferior to contemporary revascularization plus contemporary medical management using CEA, and If contemporary MEDICAL alone is not inferior to contemporary revascularization plus contemporary medical management using CAS Referrals from Primary Care Doctors Patients with a Carotid Bruit Patients with Symptomatic Contralateral Carotid Stenosis CREST-2 Your Own Clinic: Asymptomatic Patients being Followed long-term Patients with Atherosclerosis in other Vascular Beds - Coronary Artery -Renal Artery - Mesenteric Arteries - Lower Extremity (PAD) For further information

9 Lacunar stroke: What s new? Mr Williams is a 64 y.o. man who presents with 24 hours of weakness on the right side No aphasia, confusion, visual field loss PMH: HTN x 15 years, DM x 5 years MRI shows small infarct in the left internal capsule No carotid stenosis, echo shows LVH Dx: Lacunar stroke SPS 3 study For patients with subcortical (lacunar) strokes defined by clinical symptoms and MRI Compared aspirin alone vs. aspirin + clopidogrel 3020 patients enrolled No advantage with dual antiplatelet therapy SPS 3 study For patients with subcortical (lacunar) stroke Compared two blood pressure targets SBP vs. SBP<130 Patients followed for >2 years BP guideline for lacunar stroke For patients with a recent lacunar stroke, it might be reasonable to target a systolic BP < 130 mm Hg Class IIb SPS 3 Conclusions Dual antiplatelet therapy not superior to aspirin alone for long-term prevention Lower BP target (SBP<130) had trend toward lower stroke rate Lower BP target associated with reduced rate of cerebral hemorrhage No difference in MI, overall vascular events Cryptogenic stroke scenario Ms. Parker is a 65 y.o. woman who notices onset of mild right hand weakness and mild speech difficulty; NIHSS 2 Seen by stroke team, too mild for tpa MRI shows small left frontal infarct MRA, 2 D echo negative TEE shows small PFO with right to left shunt; no atrial septal aneurysm Hypercoag. work-up negative

10 RESPECT PFO Study Patients Stroke of unknown cause ( cryptogenic ) Randomized to antithrombotic therapy alone vs. antithrombotic therapy + PFO closure 980 patients enrolled Median follow-up 2.1 years RESPECT PFO Main Results Medical PFO closure P value Stroke 16 events 9 events year estimated Stroke rate 3.0% 1.6% Serious AE s 21.6% 23.0% 0.65 Atrial fibrillation 1.5% 3.0% 0.13 PFO closure: Other points to consider Rate of stroke relatively low with medical therapy At two years, number needed to treat of 71 PFO closures to prevent one stroke Subsequent strokes may not be due to the PFO PFO Recommendation For patients with a cryptogenic stroke or TIA and evidence of a PFO, available data do not support a benefit for PFO closure Class III Monitoring for AF For patients with an ischemic stroke or TIA with no other apparent cause, prolonged rhythm monitoring (approximately 30 days) for AF is reasonable within 6 months of the index event Class IIa EXPRESS TIA Study Phase I: TIA/minor stroke clinic appt-based, faxes from primary care Recommendations made regarding care Usually faxed to PMD within 24 hrs Testing arranged during following week Phase II: Aggressive TIA/minor stroke clinic No appt necessary, immediately send pts when dx made Given ASA in the office, and scripts to go home Head CT in clinic if needed

11 Conclusions Multi-modality therapy is recommended after TIA Urgent MRI can be useful if the diagnosis is not clear Antiplatelet therapy, statins, and antihypertensive meds for most patients Selective use of anticoagulants Selective use of CEA