Clopidogrel with Aspirin in Acute

Minor Stroke or Transient Ischemic

Attack

PEMBIMBING: DR. ELISA, SP.S

MARTINUS V TJANDRA
112015177
 Backgrounds

The risk of another stroke occuring after a TIA or

minor stroke is high (10-20%), having a stroke within
3 months after the index event, most of these occur
within first 2 days
The role of antiplatelet therapy for secondary stroke
prevention has been well established. However,
aspirin is the only antiplatelet agent been studied in
the acute phase of stroke, during Aspirin and
clopidogrel synergistically inhibit platelet aggregation
reduces the risk of recurrent ischemic events in
patients with the acute coronary syndrome.
 Backgrounds

Large-scale trials of secondary prevention of ischemic

events after stroke have not shown a benefit of the
combination of clopidogrel and aspirin.
They included patients with strokes of moderate
severity
We conducted the Clopidogrel in High-Risk Patients
with Acute Nondisabling Cerebrovascular Events
(CHANCE) trial to test 3 months of treatment with a
combination of clopidogrel and aspirin would reduce
the risk of recurrent stroke, as compared with aspirin
alone
 Methods Study Oversight

There was no confidentiality agreement between the

study sponsor and the investigators.All the
participants informed consent
 Study Population

Inclusion criteria :
age of 40 years or older
diagnosis of an acute minor ischemic start the study drug
within 24 hours after symptom onset
Acute minor stroke was defined by a score of 3 or less at the
time of randomization on NIHSS (higher scores indicating
greater deficits)
TIA was defined as focal brain ischemia with resolution of
symptoms within 24 hours after onset plus a moderate-to-high
risk of stroke recurrence which asses the risk of stroke on the
basis of age, blood pressure, clinical features, duration of TIA,
and presence or absence of diabetes
 Study Population

All patients underwent CT) or(MRI) of the head

Excluded if they had any of the following:
hemorrhage vascular malformation
tumor, abscess, or other major nonischemic brain disease
isolated visual changes, dizziness or vertigo without evidence of acute
infarction score of more than 2 on the modified Rankin scale (scores
range from 0 [no symptoms] to 6 [death]
NIHSS score of 4 or more a clear indication for anticoagulation therapy
history of intracranial hemorrhage
heparin therapywithin 10 days
gastrointestinal bleeding or major surgery within the previous 3 months
TIA or minor stroke caused by angiography or surgery
severe noncardiovascular coexisting condition, with a life expectancy of
less than 3 months
 Study Patients

CHANCE was a randomized, double-blind, placebo-

controlled clinical trial conducted at 114 clinical
centers in China
Both groups received open-label aspirin on day 1,
ranging from 75 to 300 mg
Patients randomly assigned to the clopidogrel
aspirin group received a loading dose of 300 mg of
clopidogrel on day 1, followed by 75 mg per day on
days 2 through 90 aspirin at a dose of 75 mg per day
on days 2 through 21
Placebo aspirin on days 22 through 90
 Study Patients

Patients randomly assigned to the aspirin group

received a placebo version of clopidogrel on days 1
through 90 and aspirin at a dose of 75 mg per day on
days 2 through 90
The primary objective was to assess the effects of the
two treatment regimens on the incidence of stroke in
the first 90 days after acute minor stroke or high-risk
TIA.
 Study Outcomes

The primary efficacy outcome was a new stroke

event at 90 days secondary efficacy outcomes
included a new clinical vascular event
Vascular death was defined as death due to stroke
(SH or SNH) myocardial infarction, congestive heart
failure, pulmonary embolism, sudden death, or
arrhythmia.
 Statistical Analysis

We calculated that a sample of 5100 patients5%

overall rate of withdrawal
No patient withdrew between the time of
randomization and the administration of the first
dose of study medication
Data from patients who had no events during the
study were censored at the time of study termination
or death
We used this approach to maximize the time-
dependent information in the trial while maintaining
the ease of interpretation of risks.
 Results Study Patient and Follow Up

Between October 2009 and July 2012, a total of 41

561 patients with stroke or TIA were screened at 114
clinical sites
5170 patients were enrolled, with 2584 randomly
assigned to the clopidogrelaspirin group and 2586
to the aspirin group
Results Study Patient and Follow Up
 Results Study Patient and Follow Up

The median age was 62 years, and 33.8% of the

patients were women
A total of 65.7% of the patients had a history of
hypertension, 21.1% had diabetes, and 43.0% smokers.
The median time from the onset of the qualifying
minor stroke or TIA to randomization was 13 hours
A total of 36 patients (0.7%) 20 in the clopidogrel
aspirin group and 16 in the aspirin group were lost
to follow-up
165 patients (6.4%) in the clopidogrelaspirin group
and 146 (5.6%) in the aspirin group discontinued the
study medication before the end of the study
 Primary Outcome

Stroke occurred in 212 patients (8.2%) in the

clopidogrelaspirin group, as compared with 303
patients (11.7%) in the aspirin group
Fatal or disabling stroke occurred in 135 patients
(5.2%) in the clopidogrelaspirin group and in 177
(6.8%) in the aspirin group
Ischemic stroke occurred in 204 patients (7.9%) in
the clopidogrelaspirin group and in 295 (11.4%) in
the aspirin group
Hemorrhagic stroke occurred in 8 patients in each of
the two study groups
Primary Outcome
 Bleeding Events

Moderate or severe hemorrhage defined by means of

GUSTO criteria, occurred in 7 patients in clopidogrel
aspirin group and 8 in aspirin group
Probability of Survival Free of Stroke
 Discussion

In this large-scale trial involving patients with high-

risk TIA or minor ischemic stroke
Found that the addition of clopidogrel to aspirin
within 24 hours after symptom onset reduced the
risk of subsequent stroke by 32.0%
Combination therapy with clopidogrel and aspirin,
as compared with aspirin alone, was not associated
with an increased incidence of hemorrhage, although
there was a worrisome trend in overall bleeding
toward more events with the combination therapy.
 Discussion

The results of our trial differ from those of other trials.

Unlike previous trials, our trial targeted a population at
particularly high risk for recurrent ischemia and at low risk
for hemorrhage.
Previous trials included patients with more severe strokes
than our trial did, and they did not enroll patients in the
first hours after an index minor stroke or TIA
This suggests that the requirement for randomization
within 24 hours after the onset of symptoms was important
In clinical practice, treatment with clopidogrel and aspirin
as soon as possible after symptom onset is likely to produce
the greatest absolute benefit
 Discussion

Several common clinical conditions mimic TIA,

including seizures, migraine, peripheral vertigo,
syncope, and anxiety
To minimize the risk of enrolling patients with TIA
mimics, we excluded all patients with isolated
sensory symptoms, isolated visual changes, or
isolated dizziness or vertigo without evidence of
acute infarction on baseline CT or MRI of the head
 Conclusion

Our study shows that among patients with high-risk

TIA or minor ischemic stroke who are initially seen
within 24 hours after symptom onset
Treatment with clopidogrel plus aspirin for 21 days,
followed by clopidogrel alone for a total of 90 days, is
superior to aspirin alone in reducing the risk of
subsequent stroke events
The combination of clopidogrel with aspirin did not
cause more hemorrhagic events in this patient
population than aspirin alone