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POINT Trial

This is a powerpoint presesntation on The POINT trial which is a landmark trial in stroke prevention.

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Ruta
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207 views27 pages

POINT Trial

This is a powerpoint presesntation on The POINT trial which is a landmark trial in stroke prevention.

Uploaded by

Ruta
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF, TXT or read online on Scribd
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Role of DAPT in prevention of

ischemic stroke – the POINT


trial
DR RUTA SAVAJ
BACKGROUND

• Risk of ischemic stroke: 3 to 15% in the 90 days after a minor


ischemic stroke or a transient ischemic attack (TIA)

• Aspirin reduces risk of recurrence by 20%

• Two trials for DAPT between 2009 – 2018 :


1. The CHANCE trial
2. The POINT trial
• 2009-2012
• 5170 Chinese patients
• Group 1 received DAPT for 21 days f/b Clopidogrel
monotherapy
• Group 2 received Aspirin monotherapy
• 32% lower risk of stroke recurrence among patients who were
treated within 24 hours after a minor ischemic stroke or TIA
with DAPT without increased risk of hemorrhagic complications
• The POINT trial: Platelet-Oriented Inhibition in New TIA and
Minor Ischemic Stroke
• 2010-2017
• 4881 patients
METHODS

• Prospective, randomized, double-blind, multicenter trial


• 4881 patients from 269 sites in 10 countries in North
America, Europe, Australia, and New Zealand
• Sponsored by the National Institute of Neurological Disorders
and Stroke (NINDS)
• Sanofi provided the clopidogrel and matching placebo
INCLUSION
CRITERIA
1. Patients with age >= 18 years and either:
a. High risk TIA: Complete resolution of the deficit at the time of
randomization AND ABCD2 score >= 4 OR
b. Minor ischemic stroke: residual deficit with NIHSS <3 at the time of
randomization

2. Ability to randomize within 12 hours of onset


3. CT or MRI ruling out hemorrhage or other pathology (vascular
malformation/tumor/abscess) that could contraindicate therapy.
EXCLUSION
CRITERIA
1. TIA limited to isolated numbness, visual changes or dizziness
alone.
2. Thrombolysis within 1 week prior to event
3. A candidate for thrombolysis, endarterectomy or
endovascular intervention, unless the subject declines
intervention at the time of evaluation for eligibility.
EXCLUSION
CRITERIA
4. Clear indication for anticoagulation anticipated during the study
period (atrial fibrillation, mechanical heart valve, DVT/PE, APLA
syndrome, hypercoagulable state)

5. Contraindication to clopidogrel or aspirin

6. Anticipated requirement for long-term (>7 days) NSAIDs

7. Inability to swallow medicines

8. At risk of pregnancy
RANDOMIZATION

• Patients were randomly assigned in a 1:1 ratio to receive either


clopidogrel plus aspirin or placebo plus aspirin

• Randomization took place centrally and electronically via the WebDCU™


clinical trials management system housed at the POINT Statistics and Data
Coordinating Center at the Medical University of South Carolina (MUSC)
Study Flowchart

St
SAMPLE-SIZE CALCULATION

• A sample of 4150 patients would provide the trial with 90%


statistical power.

• As primary endpoint event rate in the trial was low , sample size
was increased to 5,840 participants and the statistical power was
reduced from 90% to 80%.
TRIAL
DISCONTINUATION
• In December 2017, the prespecified boundary for a safety signal
of major hemorrhage was exceeded.

• At the time that the trial was halted, 4881 patients had been
enrolled, which represented 83.6% of the anticipated number of
patients
OUTCOMES

Primary efficacy outcome: Secondary efficacy outcomes:


• Risk of a composite of new • Ischemic stroke
ischemic events: ischemic
• Myocardial infarction
stroke, MI or death due to
• Death from ischemic vascular causes
ischemic vascular events upto
90 days. • Ischemic or haemorrhagic stroke
• Composite of ischemic stroke,
myocardial infarction, death from
ischemic vascular causes, or major
haemorrhage
SAFETY END POINTS

• Risk of major hemorrhage, which was defined as :


1. Symptomatic intracranial hemorrhage
2. Intraocular bleeding causing vision loss
3. Need for hospitalization
4. Death due to haemorrhage
CHARACTERISTICS AT
BASELINE
CHARACTERISTICS AT BASELINE
CHARACTERISTICS AT BASELINE
RESULTS
RESULT
S
EFFICACY AND SAFETY STRATIFIED BY TIME
PERIOD
CONCLUSIO
N
• Minor ischemic stroke or high-risk TIA in western population
• DAPT for 90 days
• Lower risk of a composite of ischemic vascular events
• Higher risk of major hemorrhage than patients who received
aspirin alone during the 90-day trial period
The CHANCE trial: The POINT trial:
• Chinese population • Western population
• 5170 patients • 4881 patients
• Clopidogrel loading - 300 mg • Clopidogrel loading - 600 mg
• DAPT × 21 days • DAPT × 90 days
• First dose DAPT within 24 hrs of • First dose of DAPT within 12 hrs
onset of onset
• 32% reduction of ischemic stroke • 28% reduction of ischemic stroke
compared to Aspirin alone group compared to Aspirin alone group
• No increase in major bleeding. • Increase in major bleeding.
CRITIQUE

1. Compared to CHANCE, higher loading dose and longer duration


of DAPT used. Can it lead to increased bleeding risk?

2. Can we apply it to Asian population considering higher rate of


CYP2C19 polymorphism and drug resistance?

3. Although discontinuation rates are similar in the two groups, a


trial drug was discontinued permanently in 29% of the patients
before the follow up period was completed
THANK YOU
The “POINT” here is that DAPT has a
“CHANCE” to reduce stroke recurrence if
used cautiously.

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