Acute stroke management
A. Acute stroke time windows: IV TPA = 3 or 4.5 hours (see TPA section). IA TPA = 6 hours. MERCI = 8 hours; however, IA therapies may be >8h if substantial mismatch present on MR or CT, or if posterior circulation.
• At CHS: for acute stroke < 14 hours, if Brain Attack beeper has not already been activated, immediately activate by paging 27246; for all acute and non-acute new stroke admissions or stroke consults, call UCLA stroke fellow at time of initial encounter.
• At VA: call senior backup if need help with acute stroke < 3 hours.
• at Olive View: call OV stroke fellow for acute stroke <12 hours.
• See TPA for Acute Stroke, following NIHSS page.
B. History: determine time of onset (last known well time LKWT and symptoms first observed time), symptoms, prior episodes. Sudden onset suggests embolism. Headache, loss of consciousness, nausea/vomiting raises concern for intracerebral hemorrhage.
C. Assess for risk factors: hypertension, atrial fibrillation, diabetes, hyperlipidemia, valve disease, hypercoagulable state, recent neck manipulation, tobacco use.
D. At UCLA, all acute patients should go to MRI first, if available within 15 minutes of arrival and no contraindication to MR, ordering “Interventional Stroke MRI Protocol”. If MRI not available within 15 minutes, all acute patients should instead go to multimodal CT, ordering “Reduced contrast dose Stroke CT protocol.” For non-acute, order “Stroke Protocol.” See MRI and CT Protocols in Protocols & Lists section.
E. Physical exam: NIHSS on every patient. More detailed exam on non-acute patients.
A. Do not miss evidence of bleed on CT. Useful early signs of infarction on CT: 1) blurring of gray-white junction, 2) mild sulcal effacement, 3) hyperdense MCA sign, 4) subtle hypodensity. In hyperacute setting, CT can be negative.
B. MRI findings for ischemic stroke: 1) DWI bright with corresponding ADC dark, within minutes. 2) FLAIR hyperintensity at about 8 hours. 3) May see vessel cutoff on MRA or blooming artifact on GRE. 4) Check for any signs of bleed (dark on FLAIR or GRE). 5) Check T1 Fat-sat if dissection is suspected.
III. Management of ischemic stroke
A. 0.9 NS (no dextrose!) at 75 cc/hr.
B. BP: hold antihypertensives until no neurologic worsening for 48 hours. Do not lower BP in first 24 hours unless SBP >220 or DBP > 120, or patient has acute MI, aortic dissection, or other systemic need for acute BP lowering.
C. Cardiac monitor
• CBC, chem.10, coags, fasting lipids, hs-CRP, HbA1c, troponins, TSH, urinalysis. Consider also RPR.
• Accuchecks QAC and QHS with ISS for at least 24 hours, d/c after that if normal.
• Liver panel if not yet on statin
• If young (<55): hypercoagulable workup, ANA, ESR, tox screen.
D. Studies: MRI stroke protocol (CT stroke protocol if pacer or other contraindication to MRI), EKG, CXR, cardiac echo (start with TTE, especially if h/o CAD, abnormal EKG, lacunar stroke, dysphagia; TEE for high-risk, i.e. suspected endocarditis)
E. Bedside swallow: for every patient at admission and document in chart
F. Subsequent evaluations:
• PT, OT.
• Speech pathology if patient failed bedside swallow test, or has aphasia
• If patient has UCLA primary care physician, call them to inform of admission and ask for consult
• If patient does not have UCLA PCP, consult Medicine if patient is staying for more than 24 hours or any active medical problems.
G. Medications for every non-TPA patient: Start ASA 325 (will determine Plavix or Aggrenox later with team), statin, Lovenox 40mg SC daily (use alternative if renal failure) or fondaparinux (Arixtra) 2.5mg SC daily, and H2 blocker
H. Other tests that may be ordered per stroke attending or fellow: TCD, carotid ultrasound, CT angio.
V. Complications of ischemic stroke
A. Extension of ischemia: due to progressive thrombosis or failure of collaterals. Consider endovascular recanalization, collateral support (increase IVF, add albumin, add pressors), change in antithrombotics.
B. Hemorrhagic conversion: risk factors include older age, large infarct (>5 cm), severe hypertension, coagulopathy. Antithrombotics should be held, blood pressure lowered, consider correcting coagulopathy.
C. Edema: risk factor is large infarct, peaks at 3-5 days. Head CT to assess for edema, midline shift. Elevate HOB 30 degrees, ICU transfer for hyperventilation, 3% saline, mannitol; consult neurosurgery for hemicraniectomy if indicated.
IV. Management of hemorrhagic stroke
A 0.9 NS (no dextrose!)
B. Lower blood pressure (SBP 130-180; level of evidence weak, however)
C. Consult neurocritical care, neurosurgery
D. CT angio or formal angiography to rule out AVM (if ICH) or aneurysm (if SAH)
E. Labs, tests as above. Correct coagulopathies. Start prophylactic AED for lobar hemorrhage. Intermittent compression boots for DVT prophylaxis.
F. If becoming comatose, raise HOB to 30 degrees, stat head CT. Consider intubation, hyperventilation and starting mannitol (0.25-1 g/kg infused over 5-30 min, titrated following serum Osms, >320mOsm increases risk of renal failure) while awaiting neurosurgery.
G. Once stabilized and sent out of the ICU, these patients become stroke service primaries. Check routine stroke risk factor labs if appropriate.
In some instances, a patient may require a heparin drip or low-molecular-weight heparin. Due to risk of hemorrhagic conversion, stroke patients receive a lower dose than the standard medicine doses for DVT or ACS (see heparin protocol)
Susan Shaw, Sarah Kremen,Jeffrey Saver 6/06, Christine Wong, MD 6/08, Neal Rao 5/10.
Stroke website: www.stroke.neurology.ucla.edu, click on referral link, ID:stroke, password: uclastroke. Contains all lists, protocols, policies for the stroke service.
STROKE: TPA FOR ACUTE ISCHEMIC STROKE
1. Ischemic stroke with a defined onset < 3 hours to time tPA is to be started. Per AHA guidelines as of 5/09, the window may be extended to < 4.5hrs with additional exclusion criteria (see below).
2. Measurable deficit on NIH Stroke Scale. Neurologic deficit > minimal weakness, isolated ataxia, isolated sensory deficit, or isolated dysarthria.
3. CT scan shows no evidence of intracranial hemorrhage. If early signs of new major hemisphere infarct are present (e.g. edema, mass effect, sulcal effacement), reassess time of onset! The presence of these CT findings are associated with an increased risk of hemorrhage.
1. Within past 3 months: stroke or serious head trauma. Last 21 days: GI or urinary tract bleed. Last 14 days: major surgery or serious trauma. Last 7 days: arterial puncture at a noncompressible site OR lumbar puncture.
2. History of intracranial hemorrhage, AVM, or aneurysm.
1. Rapidly improving neurologic signs or minor symptoms. 2.
2. SBP > 185 OR DBP > 110 OR aggressive (IV) treatment required to reduce patient’s blood pressure to specified limits.
3. Seizure at onset.
4. Symptoms suggestive of subarachnoid hemorrhage.
5. Recent myocardial infarction (post-MI) pericarditis.
1. On anticoagulation AND INR > 1.7 (PT > 15)
2. Received heparin within 48 hours preceding stroke onset AND PTT elevated.
3. Platelets < 100,000.
4. Glucose < 50 OR >400.
5. Positive pregnancy test.
Additional exclusion criteria for 3 to 4.5Hr time window:
1. Patients older than 80 years
2. All patients taking oral anticoagulants regardless of INR
3. Patients with baseline National Institutes of Health Stroke Scale score ³ 25
4. Patients with a history of both diabetes and prior stroke
Treatment and Patient Management:
1. tPA 0.9 mg/kg total or maximum 90 mg.
2. Administer 10% of tPA dose as a bolus.
3. Administer remaining 90% of tPA as a constant infusion over 1 hour.
4. NO anticoagulants or antiplatelet agents for 24 hrs from start of tPA..
NO insertion of Foley for 30 minutes after tPA administration. ÿ
NO insertion of NG tube for 24 hours after tPA administration.
Restrict central venous line placement or arterial puncture for 24 hours.
5. Blood pressure management. Post-tPA patients must be admitted to ICU!
a. Monitor BP for 24 hours after starting tPA q 15 min x 2 hrs; q 30 min x 6 hrs; then qhr for next 16 hours.
b. If SBP > 180 OR DBP > 105 in two measurements 10 min apart, then: labetalol 10-20 mg IV over 1-2 min q 10-20 min as needed up to 150 mg.
c. If DBP > 140 or labetalol not working, then IV nicardipine (5 mg/hr IV, increase by 2.5 mg/hr q5 min to max 15 mg/hr) or IV nitroprusside (0.5 to 10 mcg/kg/min). Monitor closely!
d. If a sudden major rise in BP occurs, consider intracerebral hemorrhage, stopping tPA infusion, and obtaining stat CT scan.
-s/p IV tPA: MRI at 3h & 24h
-s/p intervention: stat CT, MRI at 3h, 24h, & 5 days
TICI (Thrombolysis in Cerebral Infarction) score: established for coronary flow during PCA from the TIMI score.
TICI 0 (no perfusion) refers to the absence of any antegrade flow beyond an arterial occlusion.
TICI 1 (penetration without perfusion) is faint antegrade flow beyond the occlusion, with incomplete filling of the distal arterial bed.
TICI 2 (partial reperfusion): delayed or sluggish antegrade flow with complete filling of the distal territory. 2A < 50% distal perfusion; 2B is >50%.
TIMI 3 (complete perfusion) normal flow which fills the distal bed completely
(Confirmed with Sachin Rastogi)
ECASS (European Cooperative Acute Stroke Study*) classification for extent of bleeding and space-occupying effect after thrombolysis**.
HI1: small petechiae along periphery of the infarct
HI2: confluent petechiae within the infarct, no space-occupying effect
PH1: bleeding <= 30% infarcted area with mild space-occupying effect
PH2: bleeding > 30% infarcted area with significant space-occupying effect
PH1, PH2 with worse clinical outcome.
* JAMA. 274: 1017-1025, 1995 ** Stroke. 30(11):2280-2284, November 1999
HEPARIN PROTOCOL for STROKE NEUROLOGY
Use this protocol for all inpatients with stroke who need heparin drip, whether the heparin is for stroke or something else (e.g., DVT).
Start heparin with a bolus (upon recommendation by stroke attending/fellow) for:
• Patients with stroke progression felt possibly due to clot propagation.
• Suspected unstable basilar artery severe stenosis/occlusion.
Start heparin without a bolus for:
• Most other indications
Target PTT: 45-65
If bolus needed: 50 units/kg, (maximum 8000 units) IVP.
Initial infusion rate: 15 units/kg/hr IV, (maximum 2000 units/hr).
Follow-up dosing (rounded to nearest 50 units/hr):
PTT < 35 secs: Increase heparin by 3 units/kg/hr
PTT = 35-44 secs: Increase heparin by 2 units/kg/hr
PTT = 45-65 secs: No change
PTT = 66-90 secs: Decrease heparin by 2 units/kg/hr
PTT > 90 secs: Hold infusion for 1 hr, then restart heparin reduced by 3 units/kg/hr
Check PTT 4 hours after start and after any dose change.
Check PTT at least q12 hours on all patients.
Check CBC with platelets qd while on heparin.
Guaiac all stools while on heparin.
LMW HEPARIN DOSING PROTOCOL for STROKE NEUROLOGY
DVT Prophylaxis Dose: Lovenox 30mg SQ BID or 40 mg SQ daily
Stroke Prevention Dose: Lovenox 1mg/kg SQ BID or Dalteparin 100-120 IU/kg BID
HELPFUL TIA ADMISSION CRITERIA (ABCD2 score):
A simple score to identify individuals at high early risk of stroke after TIA
· A (Age); 1 point for age >60 years,
· B (Blood pressure > 140/90 mmHg); 1 point for HTN at acute evaluation,
· C (Clinical features); 2 points for unilateral weakness, 1 for speech disturbance without weakness, and
· D (symptom Duration); 1 point for 10–59 minutes, 2 points for >60 minutes.
· D (Diabetes); 1 point
Total scores ranged from 0 (lowest risk) to 7 (highest risk).
*Estimated ischemic stroke risk at 2 days:
· Scores 0-3: low risk, ~1%
· Scores 4-5: moderate risk, ~4%
· Scores 6-7: high risk, ~8%
Updated by Neal M Rao 6/10
STROKE RISK WITH A-FIB (CHADS2 SCORE):
STROKE AND VASCULAR NEUROLOGY LABS
Hypercoagulable work up:
DRVVT (Lupus Anticoagulant)
b2 Glycoprotein 1 Antibodies
Protein C Functional Activity
Protein S Functional Activity
Activated Protein C Resistance (Factor V Leiden if abnormal)
DRVVT (Lupus Anticoagulant)
b2 Glycoprotein 1 Antibodies
Prothrombin Gene Mutation 20210A
Factor VIII Level
Alpha-galactosidase activity assay – if suspicious of metabolic disorder in adult causing stroke
Stroke labs: see also Stroke workup
high sensitivity CRP
Liver panel if not yet on statin.
If young (<55): hypercoagulable workup, ANA, ESR.
If cervical carotid artery dissection: alpha-1 antitrypsin (low levels could indicate connective tissue disorder)
Vasculitis work up:
Cryoglobulins (C3, C4, cryocrit)
immune complex labs
STROKE: PERIOPERATIVE STROKE RISK
Jethro Hu, MD. Updated by Naveed Wagle, MD, 6/07
Perioperative stroke data is limited.
Avoid terms like “cleared for surgery.” Our job usually is to make a risk assessment (‘high,’ ‘medium,’ and ‘low’), and recommendations to reduce risk.
Stroke risk in specific situations:
Blacker et al, Mayo Clinic Proceedings 2004; 79:223-229
Stroke Index. – Perioperative stroke risk for CABG surgery
Selim, NEJM, 2007; 356:706-713.
Charlesworth DC, Ann Thorac Surg 2003;76:436-443.
Other neurological complications of cardiac surgery besides stroke:
(Arrowsmith et al, British Journal of Anesthesia 84(3): 378-93 (2000))
Fatal brain injury 0.3%
Cognitive dysfunction 30-79%
Visual field defects 25%
Recommendations for specific situations:
(adapted from Blacker et al, Mayo Clinic Proceedings 2004; 79:223-229)
1. How long should general surgery under anesthesia be delayed by stroke?
At least one month after a large ischemic stroke (greater than 1/3 distribution of MCA). Stroke causes impaired cerebral autoregulation for ~2 weeks, and recently infarcted tissue is soft and squishy and bleeds easily.
2. What to do with patients with large artery (carotid, vertebrobasilar, anterior circulation) stenosis?
If symptomatic and extracranial à treat it first (ie, with CEA or stent).
If symptomatic and intracranial à defer surgery for one month if possible.
If asymptomatic à no treatment is necessary. The risks associated of CEA and CAS, for example, are higher than the perioperative stroke risk.
If intracranial large artery stenosis in the anterior circulation à risk unknown, but is likely similar to the risk for pts with vertebrobasilar stenosis (6%).
3. What about patients with both coronary and cerebrovascular disease?
Treat the symptomatic one first.
If both are symptomatic, consider combined CABG + CEA surgery, or consider CAS first.
Anticoagulation and anti-platelet therapy:
Coumadin: Most patients with a-fib can just be started on coumadin after surgery. Only high-risk pts (includinng patients with a history of stroke) should get heparin overlap.
ASA is usually safe to continue throughout the perioperative period, except for procedures with high hemorrhagic risk.
Clopidogrel should be stopped for one week at least, preferably two.
The following tips are adapted from the UCSF Housestaff Handbook for internal medicine residents:
1. General considerations:
- Invasive surgery is generally safe (from major hemorrhagic complication) when the INR < 1.5.
- Once stopped, it takes approximately 4 days for the INR to reach 1.5.
- Once restarted, it takes approximately 3 days for the INR to reach 2.0.
- All things considered, if warfarin is held 4 days pre-op and started immediately post-op, the patient is effectively without anticoagulation for 2 days (24 hours pre-op and 24 hours post-op).
2. Risk of thromboembolism according to underlying medical condition:
- Nonvalvular atrial fibrillation: 4.5%/year (0.01%/day); note that the risk can be anywhere from 1-20%/year (0.003-0.055%/day) based on the patient’s underlying risk factors.
- Nonvalvular atrial fibrillation with previous embolism (stroke): 12%/year (0.03%/day).
- Mechanical heart valve: 8%/year (0.02%/day).
3. Management tips:
- If INR pre-op is 2-3, stop warfarin 4 days prior to surgery (withhold longer if INR > 3.0 or if it is necessary to have an INR < 1.5 pre-op).
- Measure INR one day prior to surgery: if it is > 1.8, give 1 mg vitamin K PO/SQ.
EAFT: European Atrial Fibrillation Trial (Lancet 1993;342:1255)
1007 pts; mean age, 73. Warfarin-eligible pts were randomized to warfarin (INR 2.5-4), ASA (300mg/d), or placebo.Warfarin-ineligible patients were randomized to ASA or placebo
Annual rate of stroke: 8% in warfarin group vs. 15% in ASA group vs. 19% in placebo group. Annual rate of major bleedg: 2.8% in warfarin group vs. 0.9% in ASA group.
SPAF: Stroke Prevention in Atrial Fibrillation Study (Circulation 1991; 84:527; Lancet 1994; 343:687; Lancet 1996; 348:633)
1330 pts; mean age, 67. Warfarin-eligible pts were randomized to warfarin (INR 2-3.5), ASA (325 mg/d), or placebo. Warfarin-ineligible patients were randomized to ASA or placebo.
Annual rate of stroke: 2.3% in warfarin group vs. 7.4% in placebo group. Annual rate of stroke in warfarin-ineligible pts: 3.6% in ASA group vs. 6.3% in placebo group. Annual rate of major bleeding: 1.5% in warfarin group vs. 1.4% in ASA group vs. 1.6% in placebo group.
SPAF II: Stroke Prevention in Atrial Fibrillation(Lancet 1994; 343:687)
1100 pts (mean age, 69) with AF were randomized to warfarin (INR 2-4.5) vs. ASA (325 mg/d).
Age <75: Ischemic stroke and systemic embolism: 1.3%/yr in warfarin group vs. 1.9%/yr in ASA group. Major hemorrhage: 0.9%/yr in ASA group vs. 1.7%/yr in warfarin group.
Age >75: Ischemic stroke and systemic embolism: 3.6%/yr in warfarin group vs. 4.8%/yr in ASA group. Major hemorrhage: 4.2% in warfarin (71% of ICHs were fatal) vs. 1.6% in ASA group.
ESPS-2: European Stroke Prevention Study 2 (J Neurol Sci 1996; 143:1)
6602 pts with stroke or TIA were randomized to ASA (25mg bid), extended-release dipyridamole (200 mg bid), both, or placebo x 2 yrs.
Stroke reduction compared to placebo: ASA (18%), dipyridamole (16%), ASA + dipyridamole (37%). Compared to ASA, the combinaiton of ASA and the extended-release dipyridamole reduced stroke by 23%.
WARSS: Warfarin-Aspirin Recurrent Stroke Study (N Engl J Med 2001;345: 1444-1451)
2206 pts with prior noncardioembolic ischemic stroke were randomized to warfarin (INR 1.4-2.8) or ASA (325 mg/d). Primary endpoint: recurrent ischemic stroke or death from any cause at 2 years.
No difference between groups with respect to the primary endopoint (warfarin 17.8% vs. ASA 16%) or the rate of major hemorrhage.
WASID-Prospective Warfarin-Aspirin Symoptomatic Intracranial Disease Study Prospective (N Engl J Med 2005; 352(13): 1305-1316)
Pts with TIA or stroke caused by angiographically verified 50-99% stenosis of a major intracranial artery randomized to receive warfarin (target INR, 2.0-3.0) or ASA (1300 mg/d).
Study stopped after 569 pts enrolled due to increased adverse events in warfarin arm. During a mean f/u period of 1.8yrs, death occurred in 9.7% of pts treated with warfarin (vs. 4.3% in ASA group, p=0.02). Major hemorrhage occurred in 8.3% (warfarin) vs. 3.2% (ASA) (p=0.01). The primary endpoint occurred in 22.1% of pts in ASA group and 21.8% of those in warfarin group.
HAEST: Heparin in Acute Embolic Stroke Trial (Lancet 2000; 335: 1205)
449 pts with acute ischemic stroke within 30 days and AF were randomized to dalteparin (100 IU/kg SQ bid) vs. ASA (160 mg/d)
No difference in recurrent ischemic stroke or hemorrhage rates between groups at 14 days.
International Stroke Trial (Lancet 1997; 349:1569)
19,435 pts with acute ischemic stroke were randomized to ASA (300 mg/d), subcutaneous heparin (5000 units bid or 12,500 units bid), ASA plus heparin, or neither.
ASA-treated pts had slightly fewer deaths at 14 days (9.0 vs. 9.4%), significantly fewer recurrent ischemic strokes at 14 days (2.8% vs. 3.9%), and no excess of hemorrhagic strokes (0.9% vs. 0.8%). Pts receiving heparin had fewer deaths or recurrent strokes; however, there were more hemorrhagic strokes and serious extracranial hemorrhage, mostly in the higher-dose heparin group, resulting in no net benefit for heparin. Anticoagulant monitoring and brain imaging were suboptimal.
Pooled Analysis of ATLANTIS, ECASS and NINDS rt-PA Stroke Trials (Lancet 2004; 363: 768-774)
Pooled data from six randomized placebo-controlled trials of IV tPA, with a total of 2775 pts. Using multivariable logistic regression the relation between the interval from stroke onset to start of treatment and favorable 3-month outcome and on the occurrence of clinically relevant parenchymal hemorrhage was assessed.
Odds ratio of a favorable 3-month outcome increased as onset to treatment time decreased (p=0.005). There was a statistically positive benefit to 4.5h.Onset to treat time OR for Good Outc
0 - 90 min 2.8
91 - 180 min 1.6
181 - 270 min 1.4
271 - 360 min 1.2
Hemorrhage was seen in 82 (5.9%) rt-PA pts and 15 (1.1%) controls (p=0.0001). Hemorrhage risk was not associated with onset-to-treatment time but was associated with increased age.
ATLANTIS: Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (JAMA 1999;282:2019)
613 pts with acute ischemic stroke within 3-5h were randomized to tPA or placebo.
No significant difference in functional recovery at 90 days between groups. Risk of symptomatic ICH was increased with tPA.
ECASS II: European Cooperative Acute Stroke Study II (Lancet 1998; 352 9136: 1245-1251)
800 pts with acute ischemic stroke <6 h randomized to 0.9 mg/kg tPA or placebo.
Nonsignificant trend to more favorable disability outcomes in treated pts; post hoc analysis found an abosolute reduction of death and dependency of 8.3% (p=0.024) in tPA-treated pts.
ECASS III: European Cooperative Acute Stroke Study III (N Engl J Med 2008; 359: 1318-1329)
821 pts with acute ischemic stroke 3-4.5h from onset, randomized to tPA 0.9 mg/kg or placebo. Exclusions: Age ≥ 80, severe stroke (NIHSS>25), the combination of prior stroke and diabetes, oral anticoagulant (whether INR elevated or not), platelet count < 100,000.
tPA-treated pts had a 7% absolute increase (15% relative) in the odds of minimal or no disability (p=0.04). Symptomatic ICH greater in treated group (2.4% vs. 0.2%; p=0.008).
NINDS tPA trial: National Institute of Neurological Disorders and Stroke tPA trial (N Engl J Med 1995; 333: 1581; Stroke 1998; 29: 288)
291 pts with acute ischemic stroke <3h were randomized to tPA (0.9 mg/kg IV over 1h; 10% of total dose given as a bolus; maximum dose, 90 mg) or placebo and assessed for 4-point improvement in NIHSS score or the resolution of neurologic deficit within 24h. 333 pts received IV tPA within 3h of symptoms onset and were assessed for functional and clinical outcome at 3 months. Almost 50% of pts were treated within 90 min of stroke onset.
No difference in neurologic improvement at 24h, but pts given tPA were 30% more likely than controls to have minimal or no disability at 3 mo, despite more symptomatic ICH at 36h (6.4% vs. 0.5%). Overall, there was no difference in mortality at 3 mo (tPA 17% vs. placebo 21%). No vascular imaging was reported.
NASCET I: North American Symptomatic Carotid Endarterectomy Trial (N Engl J Med 1991; 325: 445)
695 pts with 70-99% carotid stenosis and TIA or minor stroke within 120 days were randomized to carotid surgery plus postoperative antiplatelet therapy vs. medical therapy.
Surgery resulted in a marked reduction in ipsilateral stroke at 2 years (9% vs. 26%, p<0.001).
NASCET II: North American Symptomatic Carotid Endarterectomy Trial (N Engl J Med 1998; 339: 1415)
2226 pts with moderate stenosis (30-49% or 50-69%) and TIA or nondisabling ipsilateral stroke were randomized to surgery or medical therapy.
For pts with 50-69% stenosis, surgery resulted in a modest reduction in ipsilateral stroke at 5 years (15.7% vs. 22.2%; p=0.045). Benefit was greater in men than in women. For patients with 30-49% stenosis, there was no significant benefit to surgery.
MERCI: Mechanical Embolus Removal in Cerebral Ischemia (Stroke 2005; 36: 1432-1440)
151 pts with large-vessel occlusions (51% MCA, 31% ICA, 9% vertebrobasilar), who underwent embolectomy with the MERCI retrieval device within 8h or symptom onset. Pts were ineligible for IV tPA.
Recanalization achieved in 46% of patients (ITT) and in 48% of pts in whom the device was deployed. Good neurologic outcomes were much more likely in pts who canalized than in pts who did not (46% vs. 10%, RR = 4.4; p<0.0001), with reduced mortality (32% vs. 54%; p=0.01). Symptomatic ICH occurred in 7.8% of pts, and procedural complications occurred in 7.1%.
SAPPHIRE: Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (N Engl J Med 2004; 351: 1493-1501)
344 pts with asymptomatic carotid stenosis ≥80% or symptomatic carotid stenosis ≥50% and at least 1 high-risk feature (age>80, heart failure, severe COPD, previous CEA with restenosis, previous radiation or radical neck surgery, or lesions distal or proximal to usual cervical locations) randomized to carotid stenting with distal embolic protection vs. CEA.
The primary endpoint (the cumulative incidence of a major cardiovascular event at 1 year - a composite of death, stroke, or MI within 30 days after the intervention, or death or ipsilateral stroke between 31 days and 1 year) occurred in 12.2% of pts who received stenting vs. 20.1% of pts who underwent endarterectomy (p=0.004 for noninferiority, and p=0.053 for superiority).
CAPRIE: Clopidogrel vs. Aspirin in Patients at Risk of Ischemic Events (Lancet 1996; 348: 1329)
19,185 pts with atherosclerotic vascular disease (MI within 35 days or ischemic stroke within 6 months before randomization, or established peripheral arterial disease) were randomized to clopidogrel (75 mg/d) or ASA (325 mg/d).
At 1.6y, clopidogrel reduced the combined endpoint of new ischemic stroke, new MI, or other vascular death by 8.7% relative to aspirin (p=0.043). Benefit was greatest in pts with peripheral artery disease (esp if prior MI).
SPARCL: Stroke Prevention by Aggressive Reduction in Cholesterol Levels (N Engl J Med 2006; 355: 549-559)
4731 pts who had had a stroke or TIA within 1-6 months before study entry, but no known CHD, and with LDL cholesterol levels of 100-190 mg/dL randomized to 80 mg of atorvastatin per day or placebo. Median follow-up was 4.9 years.
The mean LDL level during the trial was 73 mg/dL among pts receiving atorvastatin and 129 mg/dL among pts receivng placebo. There was an absolute difference of 2.2% (RRR, 16.8%; p=0.03) at 5 years in fatal or nonfatal stroke among pts randomized to atorvastatin. There were 22 more hemorrhagic strokes in the atorvastatin group.
University of California © UC Regents
Powered by the
Mobile Web Framework