Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack

Guidelines for the Prevention of
Stroke in Patients With
Stroke and Transient Ischemic Attack
Dr. Nishtha Jain
Senior Resident
Department of Neurology
GMC, Kota.

Atrial Fibrillation
• The risk of stroke among people with AF can be
estimated by use of CHADS2 or CHA2DS2–VASc.
• For CHADS2, patients with AF are classified according
to a scoring system
• congestive heart failure (1 point),
• hypertension (1 point),
• age ≥75 years (1 point),
• DM (1 point), and
• prior stroke or TIA (2 points).

• The CHA2DS2-VASc adds to stroke risk by reliably
identifying patients at very low risk.
• Additional points are assigned for an additional age
category of 65 to 74 years (1 point), female sex (1 point),
and vascular disease other than cerebrovascular
disease (1 point).
• Two points are awarded for age ≥75 years.

AF Recommendations
• For patients who have experienced an acute ischemic
stroke or TIA with no other apparent cause, prolonged
rhythm monitoring (≈30 days) for AF is reasonable within
6 months of the index event (Class IIa; Level of Evidence
C).
• VKA therapy (Class I; Level of Evidence A), apixaban
(Class I; Level of Evidence A), and dabigatran (Class I;
Level of Evidence B) are all indicated for the prevention
of recurrent stroke in patients with nonvalvular AF,
whether paroxysmal or permanent.

• Rivaroxaban is reasonable for the prevention of
recurrent stroke in patients with nonvalvular AF (Class
IIa; Level of Evidence B).
• For patients with ischemic stroke or TIA with paroxysmal
(intermittent), persistent, or permanent AF in whom VKA
therapy is begun, a target INR of 2.5 is recommended
(range, 2.0–3.0) (Class I; Level of Evidence A).

• The combination of oral anticoagulation (ie, warfarin or
one of the newer agents) with antiplatelet therapy is not
recommended for all patients after ischemic stroke or
TIA but is reasonable in patients with clinically apparent
CAD, particularly an acute coronary syndrome or stent
placement (Class IIb; Level of Evidence C).
• For patients with ischemic stroke or TIA and AF who are
unable to take oral anticoagulants, aspirin alone is
recommended (Class I; Level of Evidence A).

• The addition of clopidogrel to aspirin therapy, compared
with aspirin therapy alone, might be reasonable (Class
IIb; Level of Evidence B).
• 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 (Class
IIa; Level of Evidence B).

• In the presence of high risk for hemorrhagic conversion
(ie, large infarct, hemorrhagic transformation on initial
imaging, uncontrolled hypertension, or hemorrhage
tendency), it is reasonable to delay initiation of oral
anticoagulation beyond 14 days (Class IIa; Level of
Evidence B).

• For patients with AF and a history of stroke or TIA who
require temporary interruption of oral anticoagulation,
bridging therapy with an LMWH (or equivalent
anticoagulant agent if intolerant to heparin) is
reasonable, depending on perceived risk for
thromboembolism and bleeding (Class IIa; Level of
Evidence C).
• The usefulness of closure of the left atrial appendage
with the WATCHMAN device in patients with ischemic
stroke or TIA and AF is uncertain (Class IIb; Level of
Evidence B).

The effectiveness of warfarin for
secondary prevention was confirmed
Annual risk of stroke was reduced from
12% to 4%.

Safety and efficacy of the combination of
clopidogrel and aspirin versus warfarin in
AF
Clear superiority of warfarin (INR 2.0–
3.0) over the antiplatelet combination

The primary end point of stroke or
systemic embolism occurred in 269
patients assigned to rivaroxaban
compared with 306 patients assigned
to warfarin.
The rate of ICH
was lower for
rivaroxaban

18 000 AF patients were randomized
to dabigatran 150 mg twice daily,
dabigatran 110 mg twice daily, or
open-label warfarin.
Both doses of
dabigatran were
noninferior to
warfarin

18 201 patients with nonvalvular AF
were randomized to apixaban 5 mg
twice daily or adjusted-dose warfarin
The primary outcome of ischemic
stroke, hemorrhagic stroke, or
systemic embolism occurred in 212
patients assigned to apixaban
compared with 265 assigned to
warfarin

• In the Apixaban Versus Acetylsalicylic Acid to Prevent
Strokes study (AVVEROES), 5599 participants with
nonvalvular AF and 1 additional stroke risk factor who
were deemed unsuitable for VKA therapy were
randomized to apixaban 5 mg twice daily or aspirin.
• After 1.1 years’ mean follow-up, the trial was stopped
early based on a favorable effect of apixaban.

• The Atrial Fibrillation Clopidogrel Trial With Irbesartan for
Prevention of Vascular Events (ACTIVE A) study
compared aspirin with clopidogrel plus aspirin in 7550 AF
patients for whom VKA therapy was unsuitable.
• After a median of 3.6 years of follow-up, the
investigators observed a reduction in the rate of stroke
with combination therapy (3.3% per year compared with
2.4% per year).

• Major bleeding occurred in 251 patients receiving
clopidogrel plus aspirin (2.0% per year) and in 162
patients receiving aspirin alone (1.3% per year).
• An analysis of major vascular events combined with
major hemorrhage showed no difference between the 2
treatment options.

Percutaneous implantation of a
device to occlude the left atrial
appendage.
The primary efficacy rate was 3.0
per 100 patient-years in the
WATCHMAN group compared with
4.9 in the warfarin group.

Acute MI and LV Thrombus
• Patients with large anterior MI associated with an LV
ejection fraction <40% and anteroapical wall-motion
abnormalities are at increased risk for developing LV
mural thrombus.
• The incidence of mural thrombus is ≈15% in patients
with anterior MI and 27% in those with anterior STEMI
and an LVEF <40%.
• In the absence of systemic anticoagulation, the risk of
embolization within 3 months among patients with MI
complicated by mural thrombus is 10% to 20%.

• The duration of risk of thrombus formation and
embolization after a large MI appears to be highest
during the first 1 to 2 weeks, with a subsequent decline
over a period of up to 3 months.
• After 3 months, the risk of embolization diminishes as
residual thrombus becomes organized, fibrotic, and
adherent to the LV wall.
• However, patients with persistent mobile or protruding
thrombus visualized by echocardiography may remain at
increased risk for stroke beyond 3 months.

Acute MI and LV Thrombus
Recommendations
• Treatment with VKA therapy (target INR, 2.5; range, 2.0–3.0)
for 3 months is recommended in most patients with ischemic
stroke or TIA in the setting of acute MI complicated by LV
mural thrombus formation identified by echocardiography or
another imaging modality (Class I; Level of Evidence C).
• Treatment with VKA therapy (target INR, 2.5; range, 2.0–3.0)
for 3 months may be considered in patients with ischemic
stroke or TIA in the setting of acute anterior STEMI without
demonstrable LV mural thrombus formation but with anterior
apical akinesis or dyskinesis identified by echocardiography
or other imaging modality (Class IIb; Level of Evidence C).

• In patients with ischemic stroke or TIA in the setting of
acute MI complicated by LV mural thrombus formation or
anterior or apical wall-motion abnormalities with an LV
ejection fraction <40% who are intolerant to VKA therapy
because of nonhemorrhagic adverse events, treatment
with an LMWH, dabigatran, rivaroxaban, or apixaban for
3 months may be considered as an alternative to VKA
therapy for prevention of recurrent stroke or TIA (Class
IIb; Level of Evidence C).

Cardiomyopathy
• Patients with ischemic or nonischemic dilated
cardiomyopathy are at increased risk for stroke.
• Stroke rates may be higher in certain subgroups,
including patients with prior stroke or TIA, lower ejection
fraction, peripartum cardiomyopathy, and Chagas heart
disease.

2305 patients with sinus rhythm, heart
failure, and an LV ejection fraction
≤35% were randomized to aspirin 325
mg/d or warfarin with a target INR of
2.0 to 3.5.
There was no difference in
primary outcome event
rates between aspirin and
warfarin.

• The main findings of WARCEF were recently confirmed
in a meta-analysis of data on all 3681 patients enrolled in
the 4 randomized trials.
• In that analysis, warfarin was associated with a 41%
reduction in the risk of stroke (number needed to treat to
prevent 1 event=61) and a nearly 2-fold increase in the
risk of major hemorrhage (number needed to harm=34).

• There were more than twice as many intracranial
hemorrhages among warfarin- treated patients but the
difference was not statistically significant.
• There were no differences between warfarin and aspirin
with respect to mortality, MI, or heart failure
exacerbation.

Cardiomyopathy Recommendations
• In patients with ischemic stroke or TIA in sinus rhythm
who have left atrial or LV thrombus demonstrated by
echocardiography or another imaging modality,
anticoagulant therapy with a VKA is recommended for ≥3
months (Class I; Level of Evidence C).
• In patients with ischemic stroke or TIA in the setting of a
mechanical LVAD, treatment with VKA therapy (target
INR, 2.5; range, 2.0–3.0) is reasonable in the absence of
major contraindications (eg, active gastrointestinal
bleeding) (Class IIa; Level of Evidence C).

with either dilated cardiomyopathy (LV ejection fraction
≤35%) or restrictive cardiomyopathy without evidence of
left atrial or LV thrombus, the effectiveness of
anticoagulation compared with antiplatelet therapy is
uncertain, and the choice should be individualized (Class

with dilated cardiomyopathy (LV ejection fraction ≤35%),
restrictive cardiomyopathy, or a mechanical LVAD who
are intolerant to VKA therapy because of
nonhemorrhagic adverse events, the effectiveness of
treatment with dabigatran, rivaroxaban, or apixaban is
uncertain compared with VKA therapy for prevention of
recurrent stroke (Class IIb; Level of Evidence C).

Valvular Heart Disease
• The main proximate cause for embolic stroke in mitral
stenosis of any cause is AF, although embolism
sometimes can occur before AF develops.
• Other factors associated with increased stroke risk in
mitral stenosis include older age, left atrial enlargement,
reduced cardiac output, and prior embolic event.
• In older studies from before the era of chronic
anticoagulation, recurrent cerebral embolism was
reported in 30% to 65% of patients within 6 to 12 years.

• In the absence of AF, mitral regurgitation is probably not
associated with a significant increase in risk for first or
recurrent stroke.
• Neither aortic regurgitation nor aortic stenosis is known
to be associated with increased risk for first or recurrent
stroke in patients who are free of AF or associated mitral
valve disease.

Valvular heart disease
Recommendations
• For patients with ischemic stroke or TIA who have
rheumatic mitral valve disease and AF, long-term VKA
therapy with an INR target of 2.5 (range, 2.0– 3.0) is

• For patients with ischemic stroke or TIA who have
rheumatic mitral valve disease without AF or another
likely cause for their symptoms (eg, carotid stenosis),
long-term VKA therapy with an INR target of 2.5 (range,
2.0–3.0) may be considered instead of antiplatelet
therapy (Class IIb; Level of Evidence C).
• For patients with rheumatic mitral valve disease who are
prescribed VKA therapy after an ischemic stroke or TIA,
antiplatelet therapy should not be routinely added (Class
III; Level of Evidence C).

• For patients with rheumatic mitral valve disease who
have an ischemic stroke or TIA while being treated with
adequate VKA therapy, the addition of aspirin might be
considered (Class IIb; Level of Evidence C).
• For patients with ischemic stroke or TIA and native aortic
or nonrheumatic mitral valve disease who do not have
AF or another indication for anticoagulation, antiplatelet
therapy is recommended (Class I; Level of Evidence C).

• For patients with ischemic stroke or TIA and mitral
annular calcification who do not have AF or another
indication for anticoagulation, antiplatelet therapy is
recommended as it would be without the mitral annular
calcification (Class I; Level of Evidence C).
• For patients with mitral valve prolapse who have
ischemic stroke or TIAs and who do not have AF or
another indication for anticoagulation, antiplatelet
therapy is recommended as it would be without mitral
valve prolapse (Class I; Level of Evidence C).

Prosthetic Heart Valves
• All patients with mechanical heart valves are at
increased risk for thromboembolic events, but the risk
can be reduced with use of oral VKAs.
• The recommended INR intensity varies depending on
the type of mechanical valve, the location of the valve,
and other factors that may influence risk for embolism,
including embolic events preceding or during therapy.
• Bioprosthetic valves are associated with a lower rate of
thromboembolism than mechanical valves.

• For patients with a mechanical aortic valve and a history
of ischemic stroke or TIA before its insertion, VKA
therapy is recommended with an INR target of 2.5
(range, 2.0–3.0) (Class I; Level of Evidence B).
• For patients with a mechanical mitral valve and a history
of ischemic stroke or TIA before its insertion, VKA
therapy is recommended with an INR target of 3.0
(range, 2.5–3.5) (Class I; Level of Evidence C).

• For patients with a mechanical mitral or aortic valve who
have a history of ischemic stroke or TIA before its
insertion and who are at low risk for bleeding, the
addition of aspirin 75 to 100 mg/d to VKA therapy is
recommended (Class I; Level of Evidence B).
• For patients with a mechanical heart valve who have an
ischemic stroke or systemic embolism despite adequate
antithrombotic therapy, it is reasonable to intensify
therapy by increasing the dose of aspirin to 325 mg/d or
increasing the target INR, depending on bleeding risk
(Class IIa; Level of Evidence C).

The trial was terminated prematurely after
the enrollment of 252 patients because
of an excess of thromboembolic and bleeding
events among patients in the dabigatran
group.
The use of dabigatran in patients with
mechanical heart valves was associated with
increased rates of thromboembolic and
bleeding complications, as compared with
warfarin, thus showing no benefit and an
excess risk.

• For patients with a bioprosthetic aortic or mitral valve, a
history of ischemic stroke or TIA before its insertion, and
no other indication for anticoagulation therapy beyond 3
to 6 months from the valve placement, long-term therapy
with aspirin 75 to 100 mg/d is recommended in
preference to long-term anticoagulation (Class I; Level of
Evidence C).

• For patients with a bioprosthetic aortic or mitral valve
who have a TIA, ischemic stroke, or systemic embolism
despite adequate antiplatelet therapy, the addition of
VKA therapy with an INR target of 2.5 (range, 2.0–3.0)
may be considered (Class IIb; Level of Evidence C).

Antiplatelet Agent Recommendations
• For patients with noncardioembolic ischemic stroke or
TIA, the use of antiplatelet agents rather than oral
anticoagulation is recommended to reduce the risk of
recurrent stroke and other cardiovascular events (Class
I; Level of Evidence A).
• Aspirin (50–325 mg/d) monotherapy (Class I; Level of
Evidence A) or the combination of aspirin 25 mg and
extended-release dipyridamole 200 mg twice daily
(Class I; Level of Evidence B) is indicated as initial
therapy after TIA or ischemic stroke for prevention of
future stroke.

• Clopidogrel (75 mg) monotherapy is a reasonable option
for secondary prevention of stroke in place of aspirin or
combination aspirin/dipyridamole (Class IIa; Level of
Evidence B). This recommendation also applies to
patients who are allergic to aspirin.
• The selection of an antiplatelet agent should be
individualized on the basis of patient risk factor profiles,
cost, tolerance, relative known efficacy of the agents,and
other clinical characteristics (Class I; Level of Evidence
C).

• The combination of aspirin and clopidogrel might be
considered for initiation within 24 hours of a minor
ischemic stroke or TIA and for continuation for 90 days
(Class IIb; Level of Evidence B).
• The combination of aspirin and clopidogrel, when
initiated days to years after a minor stroke or TIA and
continued for 2 to 3 years, increases the risk of
hemorrhage relative to either agent alone and is not
recommended for routine long-term secondary
prevention after ischemic stroke or TIA (Class III; Level
of Evidence A).

• For patients who have an ischemic stroke or TIA while
taking aspirin, there is no evidence that increasing the
dose of aspirin provides additional benefit. Although
alternative antiplatelet agents are often considered, no
single agent or combination has been adequately
studied in patients who have had an event while
receiving aspirin (Class IIb; Level of Evidence C).

• For patients with a history of ischemic stroke or TIA, AF,
and CAD, the usefulness of adding antiplatelet therapy
to VKA therapy is uncertain for purposes of reducing the
risk of ischemic cardiovascular and cerebrovascular
events (Class IIb; Level of Evidence C). Unstable angina
and coronary artery stenting represent special
circumstances in which management may warrant
DAPT/VKA therapy.

Clopidogrel plus aspirin was not
significantly more effective
than aspirin alone in reducing the rate
of myocardial infarction, stroke, or
death from
cardiovascular causes.

There is no evidence that
either
of the two treatments was
superior to the other in the
prevention of recurrent
stroke.

Oral Anticoagulant Recommendation
• For patients with noncardioembolic ischemic stroke or
TIA, the use of antiplatelet agents rather than oral
anticoagulation is recommended to reduce the risk of
recurrent stroke and other cardiovascular events (Class
I; Level of Evidence A).

Aortic Arch Atheroma
• Several retrospective and prospective cohort studies that
showed that atherosclerotic plaque ≥4 mm was an
independent risk factor for recurrent stroke.
• For patients with an ischemic stroke or TIA and evidence
of aortic arch atheroma, antiplatelet therapy is

• For patients with an ischemic stroke or TIA and evidence
of aortic arch atheroma, statin therapy is recommended
(Class I; Level of Evidence B).
• For patients with ischemic stroke or TIA and evidence of
aortic arch atheroma, the effectiveness of
anticoagulation with warfarin, compared with antiplatelet
therapy, is unknown (Class IIb; Level of Evidence C).

• Surgical endarterectomy of aortic arch plaque for the
purposes of secondary stroke prevention is not
recommended (Class III; Level of Evidence C).

Arterial Dissection Recommendations
• For patients with ischemic stroke or TIA and extracranial
carotid or vertebral arterial dissection, antithrombotic
treatment with either antiplatelet or anticoagulant therapy
for at least 3 to 6 months is reasonable (Class IIa; Level
of Evidence B).
• The relative efficacy of antiplatelet therapy compared
with anticoagulation is unknown for patients with
ischemic stroke or TIA and extracranial carotid or
vertebral arterial dissection (Class IIb; Level of Evidence
B).

• For patients with stroke or TIA and extracranial carotid or
vertebral arterial dissection who have definite recurrent
cerebral ischemic events despite medical therapy,
endovascular therapy (stenting) may be considered
(Class IIb; Level of Evidence C).
• Patients with stroke or TIA and extracranial carotid or
vertebral arterial dissection who have definite recurrent
cerebral ischemic events despite medical therapy and
also fail or are not candidates for endovascular therapy
may be considered for surgical treatment (Class IIb;
Level of Evidence C).

Patent Foramen Ovale
• Patent foramen ovale (PFO) is an embryonic defect
(hole) in the interatrial septum that can be the conduit for
an embolism traveling from the deep veins of the legs or
pelvis to the brain.
• Evidence is conflicting regarding the role of atrial septal
aneurysm, and there is little evidence that the size of the
PFO defect affects stroke risk.

PFO Recommendations
• There are insufficient data to establish whether
anticoagulation is equivalent or superior to aspirin for
secondary stroke prevention in patients with PFO (Class
• For patients with an ischemic stroke or TIA and a PFO
who are not undergoing anticoagulation therapy,
antiplatelet therapy is recommended (Class I; Level of
Evidence B).

• For patients with an ischemic stroke or TIA and both a
PFO and a venous source of embolism, anticoagulation
is indicated, depending on stroke characteristics (Class I;
Level of Evidence A).
• When anticoagulation is contraindicated, an inferior vena
cava filter is reasonable (Class IIa; Level of Evidence C).

• For patients with a cryptogenic ischemic stroke or TIA
and a PFO without evidence for DVT, available data do
not support a benefit for PFO closure (Class III; Level of
Evidence A).
• In the setting of PFO and DVT, PFO closure by a
transcatheter device might be considered, depending on
the risk of recurrent DVT (Class IIb; Level of Evidence
C).

Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack

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