MD Conference Express ISC 2013 - (Page 18)
CLINICAL TRIAL HIGHLIGHTS
Addition of AMPLATZER PFO
Occluder to Medical Therapy
Is Beneficial in Patients With
Cryptogenic Stroke and PFO
Written by Emma Hitt, PhD
Cryptogenic stroke remains a major challenge for
clinicians taking care of patients who have had
strokes. Patent foramen ovale (PFO) is a contributor
to cryptogenic stroke due to paradoxical embolism
[Furlan AJ et al. N Engl J Med 2012], but the optimal
management strategy for PFO has yet to be defined
[Kitsios GD et al. Stroke 2012]. Jeffrey L. Saver, MD, David
Geffen School of Medicine, University of California
Los Angeles, Los Angeles, California, USA, reported
the results of a follow-up analysis of the RESPECT PFO
Clinical Trial [RESPECT; NCT00465270] to characterize
the qualifying and endpoint ischemic strokes.
RESPECT included patients aged 18 to 60 with PFO
who had a cryptogenic stroke within 270 days. Enrollment
continued until the 25th endpoint. Patients were randomized
to the device group (n=499) or the medical group (n=481).
The device group received closure with the AMPLATZER
PFO Occluder plus medical therapy, and the medical
group was scheduled to receive 1 of 5 medical treatment
regimens (aspirin, warfarin, clopidogrel, or aspirin with
dipyridamole); however the fifth treatment regimen of
aspirin with clopidogrel was removed from the protocol as it
was no longer included in the American Heart Association/
American Stroke Association treatment guidelines.
Patients were excluded from the trial if they had cerebral,
cardiovascular, and/or systemic conditions that suggested
mechanisms other than PFO were responsible for the stroke.
These mechanisms included atrial fibrillation, carotid
disease, cardiomyopathy, small artery disease, uncontrolled
diabetes mellitus or hypertension, arterial hypercoagulable
states, or other sources of right-to-left shunt.
Primary analysis of the trial has previously shown that
there was a 46.6% to 72.7% reduction in risk of stroke in
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April 2013
the device versus the medical therapy group [Carrol JD.
TCT 2012]. In the follow-up analysis, the basic features of
the stroke patients were similar in the device and medical
groups. The topography and lesion size of the qualifying
strokes were also well balanced between the 2 groups.
There was a trend towards magnified value of the device
compared with the medical group in patients whose
qualifying events occurred in the setting of atrial septal
aneurysms (p=0.016), a large shunt size (p=0.012), or in an
isolated superficial distribution (p=0.049).
The topography of endpoint ischemic strokes was
significantly different between the medical and device
groups. The medical group had a larger proportion of
strokes that were superficial, mixed superficial and deep,
or otherwise not small and deep in distribution compared
with the device group (p=0.04). In addition, the medical
group experienced more infarcts ≥1.5 cm (69.2%) than the
device group (14.3%; p=0.06). Figure 1 shows a general shift
towards larger lesion size in the medical group compared
with the device group.
Figure 1. Lesion Size of Endpoint Ischemic Strokes
4
Device
Medical
3
Number of Strokes
Similar results were obtained for all subgroups.
Importantly, the treatment effect does not seem to be
mitigated by the depth or size of the hematoma or the time
to surgery. There is a progressive improvement in mRS
outcomes as the amount of clot removed is increased.
Dr. Hanley believes that reduction in clot burden is a
mechanism of benefit, MIS plus tPA saves tissue at risk, and
secondary injury occurs over days—not just immediately.
“Most likely MIS plus tPA increases independence and
appears to improve function and decrease cost,” he said.
This procedure needs to be tested in a large Phase 3 trial.
2
1
0
Small
Intermediate
Moderate
Large
Massive
Increasing Infarct Size →
Reproduced with permission from JL Saver, MD.
Limitations of the RESPECT trial include the limited
power of the subgroup interaction analysis with only
25 events to explore. In addition, the work-up of endpoint
events was incomplete in some cases since some strokes
were evaluated at nonstudy centers, and all patients had
already had a complete evaluation for qualifying infarcts,
so not all tests were repeated in every patient.
Dr. Saver said, “Consideration of the neurovascular
aspects of the RESPECT trial reinforce the primary analysis.”
When patients were stringently selected to identify those
with a history of cryptogenic stroke and PFO, closure with
the AMPLATZER PFO Occluder showed evidence of benefit
over medical management alone. The device was more
effective at averting infarcts associated with a paradoxical
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Table of Contents for the Digital Edition of MD Conference Express ISC 2013
MD Conference Express ISC 2013
Contents
Defending the Stroke Guidelines
Stroke Update: An Overview of What Is Going on in the Area of Stroke
Brain Imaging Does Not Help Identify Patients Who May Benefit From Endovascular Treatments for Acute Ischemic Stroke
MISTIE II Trial: 365-Day Results Demonstrate Improved Outcomes and Cost Benefit
Addition of AMPLATZER PFO Occluder to Medical Therapy Is Beneficial in Patients With Cryptogenic Stroke and PFO
Intraoperative CT-Guided Endoscopic Surgery for ICH [ICES]
The EMBRACE Trial: Prolonged Ambulatory Cardiac Monitoring Improves the Detection and Treatment of Atrial Fibrillation in Patients With Cryptogenic Stroke
DP-b99 Does Not Improve Recovery Following Acute Ischemic Stroke
The Secondary Prevention of Small Subcortical Strokes Trial: Blood Pressure Intervention Results
Final Results of the Solitaire FR Thrombectomy for Acute Revascularization: The STAR Trial
Clopidogrel Plus Aspirin Reduces Risk of Recurrent Stroke: The CHANCE Trial
Reversal of Chronic Hypoperfusion to Improve Cognitive Function: The RECON Trial
Cardioembolic Stroke
IMS III
Novel Anticoagulants in Vascular Neurology Practice
Wake-Up Stroke
Virtual Reality in Stroke Rehabilitation
Reward Improves Long-Term Retention of a Motor Memory Through Induction of Offline Memory Gains
MD Conference Express ISC 2013
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