Page 2398 - Hematology_ Basic Principles and Practice ( PDFDrive )

2140 Part XII Hemostasis and Thrombosis

Lifestyle Modification
When Should Warfarin Be Started After Acute Ischemic
BOX 145.2 Stroke With Atrial Fibrillation?
Lifestyle modification remains a cornerstone of stroke prevention.
We initiate all patients on aspirin in the acute setting. In patients with Important components include smoking cessation, moderate physical
acute transient ischemic attack or minor ischemic stroke and in the activity, weight reduction in overweight or obese patients, adopting
absence of a large area of acute infarction, we usually initiate warfarin a healthy heart diet with increased fruit and vegetable intake, reduced
immediately, where a decision is made to use warfarin. For those with salt intake in those consuming high-salt diets, and moderate alcohol
severe stroke or moderate stroke with a large area of infarction, initiat- consumption.
ing aspirin is recommended without anticoagulant therapy in the acute
phase. Warfarin can be cautiously introduced 5–7 days after stroke
onset after hemorrhagic transformation of the infarct has been excluded PROGNOSIS
on neuroimaging in those suspected to be at increased risk of intrace-
rebral hemorrhage. For patients who have had large infarcts, evidence
of hemorrhagic transformation, progression of stroke, or uncontrolled Prognosis after stroke depends on patient age, underlying stroke
hypertension, further delays beyond 14 days poststroke may be etiology, severity of neurological deficit and level of dependence,
required prior to initiation of therapy with warfarin. We stop aspirin once and comorbidity burden. In a large cohort of over 10,000 US
a therapeutic anticoagulant effect is achieved, unless there is a compel- patients hospitalized with ischemic stroke, 1- and 4-year mortality
ling indication for combination of aspirin and warfarin (e.g., coronary rates were 24.5% and 41.3%, respectively, with rates of recurrent
stent). We do not bridge the initial period with treatment doses of stroke of 8.0% and 18.1% at 1 and 4 years, respectively. Early death
heparin, although it may be reasonable in patients with transient usually occurs because of neurological complications (e.g., cerebral
ischemic attack and atrial fibrillation, as they would be expected to be edema, raised ICP) or medical complications of dependency and
a lower risk of intracerebral hemorrhage (although unproven).
immobilization (e.g., aspiration pneumonia). Longer-term mortal-
ity is usually caused by cardiovascular disease. Two-thirds of stroke
survivors are left with chronic residual disability. In addition, patients
stroke. Oral anticoagulants are not superior to aspirin for the second- with stroke are at an increased risk of myocardial infarction, deep
ary prevention of stroke in patients with noncardioembolic stroke vein thrombosis, urinary tract infections, hip fracture, pneumonia,
(WARSS and ESPRIT) or in patients with intracranial stenosis and subsequent rehospitalization. Common complications of stroke
(WASID). in the longer term include seizure disorders, cognitive impairment
and dementia, depression, and chronic pain syndromes (e.g., central
poststroke pain).
Lipid Modification

Current guidelines recommend statin therapy in patients with LDL FUTURE DIRECTIONS
≥100 mg/dL. The SPARCL trial comparing atorvastatin 80 mg daily
with placebo reported a reduced risk of recurrent stroke over 5 years To date, our knowledge of the epidemiology of stroke has been
of follow-up in the atorvastatin group. derived from studies in North America and Europe, with compara-
tively fewer studies in middle- and low-income countries, although
the vast majority of the global burden of stroke occurs in these
Blood Pressure regions. In addition, a number of large ongoing epidemiologic col-
laborative studies (International Stroke Genetics Consortium) will
PROGRESS, the largest trial of antihypertensive therapy for second- clarify the role of genetics in the pathogenesis of stroke. Population-
ary stroke prevention, compared perindopril (with or without inda- based interventions to reduce the burden of stroke will be an
pamide) with placebo. Combination therapy reduced blood pressure important focus of future research, and will include evaluation of
by 12/5 mmHg and stroke risk by 43%, and produced greater reduc- interventions to reduce salt intake and use of combination cardiopro-
tion in blood pressure and stroke risk compared with perindopril tective therapies (e.g., Polycap) in high-risk populations. In patients
alone. Current guidelines recommend a target blood pressure of with TIA and minor ischemic stroke, a phase II trial (FASTER)
140/90 mmHg or less. suggested that combination aspirin and clopidogrel may be superior
to aspirin alone and this question will be addressed in a phase III
trial. For acute ischemic stroke, the IST-3 trial will provide important
Patent Foramen Ovale Closure information on use of thrombolysis within 6 hours of symptom onset
in a large generalizable population. Other ongoing trials will deter-
Despite the results of three randomized controlled trials, the role of mine the role of acute interventions designed to reduce the severity
PFO closure devices remains uncertain. The randomized controlled of stroke (e.g., albumin in ALIAS and hypothermic interventions).
trial CLOSURE I (n = 909) reported that PFO closure with the For secondary prevention, ongoing trials will clarify optimal anti-
STARFlex closure device (no longer clinically available) was not thrombotic therapy and target blood pressure in patients with small-
superior to medical therapy alone in reducing the risk of recurrent vessel disease (SPS-3), closure devices for PFO, and anticoagulant
TIA/stroke at 24 months (5.5% vs. 6.8%; hazard ratio [HR], 0.78; therapy for aortic arch disease (ARCH).
95% CI, 0.45–1.35), and was associated with an increased risk of
major vascular complications (3.2% vs. 0.0%; p < .001) and new-
onset atrial fibrillation (5.7% vs. 0.7%; p < .001). Furthermore, in SUGGESTED READINGS
the RESPECT trial (n = 980), PFO closure with the Amplatzer PFO
occluder was not found to be superior to medical management in Amarenco P, Bogousslavsky J, Callahan A, III, et al: High-dose atorvas-
reducing the risk of recurrent stroke or death during follow-up (1.8% tatin after stroke or transient ischemic attack. N Engl J Med 355:549,
vs. 3.3%, HR, 0.49; 95% CI, 0.22–1.11). Interestingly, PFO closure 2006.
was superior to medical management in preventing recurrent stroke Anderson CS, Chalmers J, Stapf C: Blood-pressure lowering in acute intrace-
in the subgroup of patients with a substantial shunt (0.8% vs. 4.3%; rebral hemorrhage. N Engl J Med 369(13):1274–1275, 2013.
HR, 0.18; 95% CI, 0.04–0.81) and concomitant ASA (1.1% vs. Berge E, Cohen G, Roaldsen MB, et al: Effects of alteplase on survival after
5.3%; HR, 0.19; 95% CI, 0.04–0.87), suggesting a benefit in high- ischaemic stroke (IST-3): 3 year follow-up of a randomised, controlled,
risk patients. The PC trial also did not demonstrate a benefit with open-label trial. Lancet Neurol 15(10):1028–1034, 2016.
device closure of PFO. However, low event rates in these three trials Broderick JP, Meyers PM: Acute stroke therapy at the crossroads. JAMA
have precluded a definitive conclusion. 306:2026, 2011.