STROKE PREVENTION/IN-HOSPITAL HEALTH
| FROM STENTS TO STATINS: WHAT’S NEW IN STROKE PREVENTION —Christy Jackson, MD, Associate Clinical
Professor, Department of Neurosciences, University of California, San Diego School of Medicine, and Director, Stroke Prevention,
UCSD Stroke Center
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| Impact of stroke: 750,000 new cases annually; third leading cause of death in United States (one third of new cases result
in death); leading cause of death in Asia; leading cause of disability in United States; focus on prevention; few patients
know warning signs of stroke; few admit having risk factor for stroke; aversion to outcome; survey—30% of individuals
who did not come to hospital immediately with stroke symptoms took nap (thought it would resolve symptoms; slept
through 3-hr window); 10% called primary care physician, leading to delayed care
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| Causes: embolization from heart, aorta, carotid or vertebral arteries; vertebral artery or carotid dissection, especially in patients
<45 yr of age (often due to minor trauma, eg, chiropractic maneuvers); thrombosis; small-vessel disease (thrombosis
in small penetrating arteries of brain); wall injury and plaque—initial injury; cholesterol, fibrin, platelet adherence; inflammation
(statins helpful in reducing inflammation in active plaque)
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| Prevention: lifestyle—many risk factors modifiable; difficult to get patient’s attention to individualize stroke prevention
strategy; research shows even patient told to stop smoking when walking out door 33% more likely to stop smoking;
medications—antiplatelet agents (ticlopidine, clopidogrel, dipyridamole [Persantine], dipyridamole and aspirin [Aggrenox]);
aspirin); new evidence that aspirin 100 mg every other day effective at blocking stroke in women ≥45 yr of age
and helps reduce stroke and heart attack in men and women ≥65 yr of age; statins; antihypertensive agents; surgery—
carotid endarterectomy (CEA; indicated in patients who had transient ischemic attack [TIA] or nondisabling stroke in last 6
mo referable to carotid with 50%-99% blockage); carotid stenting; nonmodifiable risk factors—age; sex (men at increased
risk early on, but more women die of stroke than men); black ethnicity; heredity; modifiable medical
conditions—hypertension; cardiac disease; atrial fibrillation (AF); hyperlipidemia; diabetes mellitus; carotid stenosis; previous
TIA or stroke (both confer highest risk for stroke in following 3 yr); modifiable behaviors—cigarette smoking;
heavy alcohol use (>2 servings/day; risk for hemorrhagic stroke); physical inactivity (guidelines suggest 1 hr of aerobic activity/day;
10,000 steps/day on pedometer )
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| Medical stroke prevention: aspirin—primary prevention with 100 mg every other day in women ≥45 yr of age who have
not had TIA or stroke; secondary prevention effective with 81 mg every day (some studies), 325 mg in other studies; evidence
that aspirin resistance develops in some individuals after 1 mo, requiring increase in dose; ticlopidine; clopidogrel, Aggrenox
(low dose of aspirin; better compliance if started with half dose for first week, then increased to help with headache side effect);
warfarin (Coumadin); Management of Atherothrombosis with Clopidogrel in High-risk patients with recent TIA
or stroke [MATCH] trial—7600 patients; clopidogrel 75 mg vs clopidogrel 75 mg plus low-dose aspirin; primary end
point vascular death, stroke or myocardial infarction (MI); results showed no difference in prevention if aspirin added to clopidogrel,
but bleeding significant in group on combined therapy; AF—sources of clots (left ventricle; left atrium; right-to-left
shunt with patent foramen ovale); patient should be on warfarin or aspirin; Stroke Prevention in Atrial Fibrillation
(SPAF-I, -II, -III)—patients with AF; event rate much higher if on placebo; concluded that if patient has no risk factors (eg,
congestive heart failure [CHF], previous embolic event, uncontrolled hypertension [HTN]) for stroke and <65 yr of age, can
use aspirin; if 65 to 75 yr of age, definitely need aspirin; >75 yr of age, suggest warfarin; any risk factor present, use warfarin
alone; Antihypertensive and Lipid Lowering treatment for the prevention of Heart Attack Trial (ALLHAT)—25,000
patients with HTN and one other risk factor for coronary artery disease (CAD); primary end point fatal or nonfatal MI; trial
negative; secondary end point combined cardiovascular disease or stroke; fewer events in diuretic arm; ALLHAT-Lipid Lowering
Treatment (LLT)—49% women in trial; pravastatin vs usual care; no significant difference; Prevention Regimen
for Effectively Avoiding Second Strokes (PROFESS)—ongoing trial; Aggrenox vs clopidogrel; HTN arm with telmisartan
(Micardis) vs placebo; primary end point time to recurrent stroke; Secondary Prevention of Small Subcortical Strokes
(SPS3)—ongoing trial; aspirin vs aspirin plus clopidogrel; aggressive (systolic blood pressure [SBP] 120 mm Hg) vs usual
care (SBP 140 mm Hg); primary end point, recurrent stroke
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| Surgical stroke prevention: asymptomatic carotid stenosis—watch longer; evaluate preoperatively for bruit and contralateral
high-grade stenosis (may operate sooner); Asymptomatic Carotid Atherosclerosis Study (ACAS)—looked at stroke
risk for large artery with 60% to 99% stenosis; with medical treatment, risk for stroke 11%, and with surgical treatment,
5.1%, conferring 54% risk reduction at 5 yr (number needed to treat [NNT] 67); for large-artery stenosis, medical treatment
associated with 6.6% risk for stroke, surgical treatment with 3.1% risk, conferring 54% risk reduction (NNT 111); so, surgery
reduces risk from 2% per year to 1% per year for 5 yr; however, since risk of surgery 3%, benefit marginal unless surgeon
highly experienced; speaker suggests physician look at asymptomatic carotid stenosis with Doppler ultrasonography; if
ulcerations and hyperechoic regions present, may send for surgery if patient good surgical candidate now, but may not be
later; put others on statins and follow with carotid ultrasonography; North American Symptomatic Carotid Endarterectomy
Trial (NASCET)—patients with TIA or nondisabling stroke; randomized to very high-dose aspirin or CEA plus aspirin;
study ended prematurely because benefit so great for 70% to 99% stenosis group with surgery; 50% to 70% stenosis
group slight benefit with surgery; 0% to 50% stenosis showed no benefit with surgery
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| Role of statins: risk for recurrent MI reduced in all trials; risk for embolic complications reduced; stroke subtypes not well
differentiated; no trials done on patients without CAD; 15% to 20% of patients with stroke have past MI; plaque regression
not proportional to clinical benefit; Reversal trial—showed effect of intensive, compared with moderate, lipid-lowering
therapy in individuals with CAD; moderate-dose group on pravastatin; high-dose group on atorvastatin; symptomatic coronary
disease; study showed high-dose statin can reduce plaque burden; Stroke Prevention by Aggressive Reduction in
Cholesterol Levels (SPARCL) Study—individuals with stroke only placed on high-dose atorvastatin (Lipitor); results
available soon
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| Carotid stenosis: Carotid Revascularization Endarterectomy vs Stent Trial (CREST)—symptomatic good-risk patients
with 50% stenosis; endarterectomy vs stent; ongoing study; no head-to-head data show stent better than endarterectomy in prevention
of stroke
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| Questions and answers: after TIA or stroke, appropriateness of surgery and information given to patients on risk of
surgery and anesthesia—endarterectomy only surgical option; in good surgical candidate, 3% risk for morbidity and
mortality in first 30 days, but 17% risk for stroke in next 2 yr; in poor surgical candidate, consider carotid stent; why not
open fully occluded artery—not studied; speaker opens fully occluded artery with fresh clot; if event week old, collateral
circulation already formed; aspirin for healthy woman with no risk factors—young, healthy woman should not
take aspirin; information to date shows primary prevention with aspirin does not help and carries 18% to 22% risk for
gastrointestinal (GI) hemorrhage; risk for hemorrhagic stroke with heavy (1-2 g/day) aspirin use—heavy aspirin dose
used in high-grade intracranial stenosis, but watch closely and back off dose if signs or symptoms of GI hemorrhage; effectiveness
of dipyridamole, aspirin (or other antiplatelet medications) vs warfarin and what is bleeding risk—
study of warfarin vs aspirin for recurrent stroke symptoms showed no difference in risk for stroke; more bleeding in warfarin
group; warfarin not used for regular thrombotic stroke, use antiplatelet agents (18%-20% risk for GI bleeding); migraines
as risk factor for stroke; use of calcium channel blockers—risk factors for stroke include migraines with
aura; these patients should not smoke or take oral contraceptives (30 times greater risk); among calcium channel blockers,
verapamil excellent; nimodipine, expensive with not much benefit over high-dose verapamil; do statins reduce
plaque size?—yes, in coronary vasculature; low-density lipoprotein (LDL) too low?—speaker believes there may be
“too low” level; cholesterol important component of blood vessel wall; if level too low, intracranial hemorrhage possible;
side effects of statins—if muscle pain and cramping occur, decrease dose or change to another statin until no symptoms
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| PREVENTING ILLNESS IN HOSPITALIZED PATIENTS —Bradley A. Sharpe, MD, Assistant Clinical Professor of
Medicine, University of California, San Francisco, School of Medicine
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| Deep venous thrombosis (DVT): estimated prevalence 10% to 20% of patients admitted for general medical illnesses
(found with screening ultrasonography); not all symptomatic; DVTs and pulmonary emboli (PEs) account for ≈10% of
in-hospital mortality; on autopsy, up to 70% to 80% of deaths caused by PE not suspected; most fatal PEs in hospital occur
in nonsurgical patients; risk factors—stasis (immobility, acute MI, CHF, paralysis, and stroke); endothelial injury
(previous venous thromboembolism, presence of central venous catheter); hypercoagulability (cancer, obesity, estrogen,
inflammatory bowel disease, systemic infection, and thrombophilias); Chest guidelines—information on anticoagulation,
including DVT prophylaxis; every person admitted to hospital should have DVT risk assessment; low-risk patients,
<40 yr of age with no risk factors; moderate-risk, >40 yr of age with 1 to 2 risk factors; high-risk, >40 yr of age with >2
risk factors (age >70 yr independent risk factor); mechanical prophylaxis—thromboembolic disease (TED) hose; intermittent
pneumatic compression (“squeezers”); risk reduction 52% in DVT using TED hose in surgical patients; no studies
of mechanical prophylaxis in medical patients; Chest guidelines recommend mechanical prophylaxis in patients with
high bleeding risk (grade 1C+); pharmacologic prophylaxis—subtherapeutic doses of heparins (including unfractionated
heparin [UFH] and low molecular weight heparin [LMWH]); 6 randomized controlled trials in moderate- to high-
risk patients showed risk reduction of 50% to 70%; studies showed UFH similar to LMWH in efficacy, bleeding risk, and
heparin-induced thrombocytopenia; LMWH costs more; guidelines—assess individual patient risk; ambulate low-risk
patients; give moderate-risk patients UFH bid or tid or mechanical prophylaxis; with high bleeding risk, give UFH tid,
LMWH, or mechanical prophylaxis
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| Stress ulcers: clear association between severe physiologic stress and GI ulceration (stress ulcer, stress gastritis);
pathophysiology—normal physiologic balance of acid buildup, enzymes, and mucosal defenses breaks down in severe
stress, eg, sepsis and acute illness, leading to stress erosions or stress gastritis; risk factors—mechanical ventilation >48
hr (relative risk 14); coagulopathy (platelets <50,000/µL or prothrombin time >1.5 times normal); sepsis or septic shock;
no association in any study with npo status, history of GI ulcer or previous GI bleeding, steroids, coffee intake, stress at
work; routine stress ulcer prophylaxis not indicated for general medicine patients; admission does not mean patient needs
famotidine (Pepcid) or proton pump inhibitor (PPI); all medications have side effects (eg, GI upset; H2 blockers can
cause altered mental status and thrombocytopenia); aspiration pneumonia; cost; no data on PPIs in preventing gastritis
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| Aspiration: defined as misdirection of oropharyngeal or gastric contents into lower respiratory tract; pneumonia develops
from colonized oropharyngeal bacteria; incidence of aspiration in hospitalized patients unknown but common; up to 20%
of all cases of pneumonia in nursing homes caused by aspiration; difficulty swallowing food and medications leading risk
factor for pneumonia; impact of hospital-acquired pneumonia—increased length of stay, health care costs, and mortality;
risk factors—altered mental status (using Glasgow Coma Scale [GCS]); dysphagia or abnormal gag reflex; poor
oral hygiene or dentition; tube feeding; poor functional status; advanced age; prevention—no consensus what “aspiration
precautions” means when written in patient’s chart; no trials of “aspiration precautions” in general medical patients;
randomized trial—86 intubated patients randomized to semirecumbent (>45º) vs supine position; measured development
of ventilator-associated pneumonia at 30 days; rate of ventilator-associated pneumonia in supine patients, 35%
(clinical) and 23% (biologic); in semirecumbent patients, rates of 8% and 5%; number needed to treat (NNT) of 4; no evidence
to support any intervention in floor patients; write orders to keep head of bed >45º at all times
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| Vaccination: influenza causes 36,000 deaths/year in United States; most significant impact on infants, elderly, and those
with comorbidities; season October to March; Centers for Disease Control and Prevention (CDC) recommends vaccination
for all adults >65 yr of age, adults of any age with chronic medical conditions (eg, chronic obstructive pulmonary
disease, asthma, diabetes), patients in long-term care facilities, immunosuppressed patients, and health care workers;
many of patients seen in hospital >65 yr of age and have chronic medical condition; these patients target for influenza
vaccine; efficacy—vaccine prevents influenza in up to 70% to 90% of patients <65 yr of age; not as efficacious in those
>65 yr; much evidence that people who get vaccine have reduced rate of developing influenza; study showed that after
controlling for other risk factors, comparing patients vaccinated vs not vaccinated, vaccinated patients had reduction in
cardiac hospitalization, stroke, pneumonia, and mortality; estimated vaccination rates for 2000 to 2001—adults ≥65
yr of age, 66%; high-risk adults age 50 to 64 yr, 44%; high-risk adults 18 to 19 yr of age, 23%; goals of CDC by 2010, increase
numbers to 90%, 60%, and 60%; vaccinating patients as preventive medicine, shifting from outpatient to inpatient
setting (captive audience); study in 2002 showed 2% of eligible patients vaccinated before discharge; inpatient
vaccination—proven equivalent immunogenicity; safe and cost-effective; CDC recommends not giving vaccination
when patient febrile; standing orders (computer generates order) most effective
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Educational Objectives
| The goal of this program is to provide the listener with information on current practice in stroke prevention and ways to prevent
illness in hospitalized patients. After hearing and assimilating this program, the clinician will be better able to:
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 | 1. Discuss modifiable lifestyle risk factors for stroke.
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| 2. Describe the medical preventive measures for stroke, including the role of statins.
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| 3. Discuss the role of surgery in prevention of stroke.
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| 4. Discuss prevention of common complications in hospitalized general medicine patients.
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| 5. Apply outpatient preventive medicine in the inpatient setting.
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Discussed on This Program
Aspirin (acetylsalicylic acid; ASA) [many trade names]
Atorvastatin calcium [Lipitor]
Clopidogrel bisulfate [Plavix]
Dipyridamole [Persantine, Persantine IV]
Dipyridamole and aspirin [Aggrenox]
Famotidine [Pepcid, Pepcid AC, Pepcid RPD]
Heparin sodium injection
Influenza virus vaccine [FluMist, FluShield, Fluvirin, Fluzone]
Low molecular weight heparins [dalteparin (Fragmin); enoxaparin (Lovenox); tinzaparin (Innohep)]
Nimodipine [Nimotop]
Pravastatin sodium [Pravachol]
Sucralfate [Carafate]
Telmisartan [Micardis]
Ticlopidine HCl [Ticlid]
Verapamil HCl [many trade names]
Warfarin sodium [Coumadin]
Suggested Reading
Berry BB, et al: Influenza vaccination is safe and immunogenic when administered to hospitalized patients. Vaccine
19:3493, 2001; CaRESS Steering Committee: Carotid revascularization using endarterectomy or stenting systems (CaRESS)
phase I clinical trial: 1-year results. J Vasc Surg. 42:213, 2005; Cramer SC: Patent foramen ovale and stroke: prognosis
and treatment in young adults. J Thromb Thrombolysis 20:85, 2005; Geerts WH, et al: Prevention of venous
thromboembolism. The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 126:338s, 2004; Imray
CH, Tiivas CA: Are some strokes preventable? The potential role of transcranial Doppler in transient ischemic attacks
of carotid origin. Lancet Neurol 4:580-6, 2005; Jamieson DG, et al: Review of antiplatelet therapy in secondary prevention
of cerebrovascular events: a need for direct comparison between antiplatelet agents. J Cardiovasc Pharmocol Ther. 10:153,
2005; Koebbe CJ, et al: The role of carotid angioplasty and stenting in carotid revascularization. Neurol Res 27 Supp 1:53,
2005; Laheij RJF, et al: Risk of community acquired pneumonia and use of gastric acid-suppressive drugs. JAMA
292:1955, 2004; Lip GY, Edwards SJ: Stroke prevention with aspirin, warfarin and ximelagatran in patients with non-valvular
atrial fibrillation: A systemic review and meta-analysis. Thromb Res Sep 28, 2005 [Epub ahead of print]; Merli GJ:
Pulmonary embolism in medical patients: improved diagnosis and the role of low-molecular-weith-heparin in prevention and
treatment. J Thromb Thrombolysis 18:117, 2004; Onalan O, et al: Nonpharmacologic stroke prevention in atrial fibrillation.
Expert Rev Cardiovasc Ther 3:619, 2005; Penner Rm, et al: Best evidence in critical care medicine: Stress ulcer prophylaxis
in the intensive care unit: damned if you do, damned if you don’t. Can J Anaesth 52:650, 2005; Stollman N, Metz
DC: Pathophysiology and prophylaxis of stress ulcer in intensive care unit patients. J Crit Care 20:35, 2005; White CJ: Carotid
artery intervention. Minerva Cardioangliol 53:473, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship
with the manufacturer or provider of any commercial product or service discussed. For this issue, the faculty reports
nothing to disclose.
Dr. Jackson was recorded at Topics in Internal Medicine, held March 3-9, 2005, in San Diego, California, and sponsored by
the University of California, San Diego, School of Medicine. Dr. Sharpe was recorded at the 33rd Annual Advances in Internal
Medicine, held May 25-28, 2005, in San Francisco, California, and sponsored by University of California, San Francisco,
School of Medicine. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the
production of this program.
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