March 30, 2023 Stroke Conference

Cara Camille Matute, MD

Oral anticoagulation reduces the rate of systemic
embolism for patients with atrial fibrillation by
two-thirds, but its benefits for patients with
previous intracranial hemorrhage are uncertain

Aimed to establish whether starting oral

Background
anticoagulation is non-inferior to avoiding oral
anticoagulation for survivors of intracranial
of the study
hemorrhage who have atrial fibrillation
EVIDENCE BEFORE THIS STUDY
NASPAF-ICH
NOACs for Stroke Prevention in Patients With Atrial
Fibrillation and Previous ICH
Feasibility study of a controlled trial examining the
efficacy and safety of NOACs compared with ASA for
stroke prevention in patients with atrial fibrillation and
previous intracerebral hemorrhage
30 patients, single-center in Canada, 1 yr follow-up
APACHE-AF
Apixaban versus Antiplatelet drugs or no
antithrombotic drugs after Anticoagulation-
associated intraCerebral HaEmorrhage in patients
with Atrial Fibrillation
Feasibility study aimed to estimate rates of
vascular death or non-fatal stroke in patients with
atrial fibrillation and a recent anticoagulation-
associated ICH treated with apixaban and in
those in whom oral anticoagulation is avoided
101 patients, 14 hospitals in the Netherlands, 1 yr
follow-up

compared the effects of starting oral anticoagulation versus antiplatelet therapy

or no antithrombotic therapy for participants with atrial fibrillation after
intracerebral hemorrhage, but were inconclusive about safety and efficacy
 Survivors of spontaneous ICH: at higher risk of
ischemic stroke and myocardial infarction, and all
major vascular events

Significance Atrial fibrillation: 14–42% of patients with any type

of ICH and more than doubles the risk of major
vascular events

Patients on anticoagulation (whether VKA or DOAC):

higher risk of ICH than general population and more
likely to be fatal with anticoagulant use
Oral vitamin K antagonist warfarin: 64% relative
reduction in the risk of stroke in atrial fibrillation
DOAC reduces stroke risk, ICH and death compared
with warfarin for patients with atrial fibrillation
Methodology
Prospective, randomized, open-label, assessor-masked, parallel-group, pilot-
DESIGN phase, non- inferiority trial
Done at 67 hospitals in the UK

PARTICIPANTS Inclusion and exclusion criteria

Computerized randomization system assigned participants 1:1 to either start or

avoid full treatment dose oral anticoagulation
Treatment allocation was known to participants, clinicians caring for them in
RANDOMIZATION AND MASKING primary and secondary care, and local investigators
Outcome event adjudicator was masked to participant identity, treatment
allocation, and drug use by redaction of this information from source
documents
 INCLUSION CRITERIA EXCLUSION CRITERIA

1. Symptomatic intracranial hemorrhage within the last 24 hours

2. Symptomatic intracranial hemorrhage is exclusively due to trauma or
1. Patient age ≥18 years
hemorrhagic transformation of ischemic stroke
2. Symptomatic intracranial hemorrhage
3. Prosthetic mechanical heart valve or severe native valve disease
Not attributable to a known underlying
4. Left atrial appendage occlusion for prevention of systemic embolism in AF
intracranial aneurysm, arteriovenous
done in the past, or intended to be performed
malformation, cerebral cavernous
5. Intention to start antiplatelet drug(s) if randomized to start full dose OAC
malformation, dural arteriovenous fistula,
6. Intention to start OAC or parenteral anticoagulation
intracranial venous thrombosis
7. Intention to implement the allocated treatment strategy for <1 yr
Not attributable to known head injury
8. Patient or their doctor is certain about whether to start or avoid full dose OAC
Brain imaging appearances consistent with
9. Brain imaging that first diagnosed the intracranial hemorrhage is not available
spontaneous intracranial hemorrhage
10. Patient is not registered with a general practitioner
3. Atrial fibrillation/flutter (persistent or
11. Patient is pregnant, breastfeeding, or of childbearing age and not taking
paroxysmal) with a CHA2DS2-VASc score ≥2
contraception
4. Scan must be done after symptomatic ICH and
12. Patient and carer unable to understand spoken or written English
before randomization
13. Life expectancy less than one year
14. Previously randomized in SoSTART
Methodology
Procedures
1 Informed Consent and brain MRI read by Neuroradiologist (masked)

2 Randomization

Intervention: oral anticoagulation for atrial fibrillation

DOAC (factor Xa inhibitor or direct thrombin inhibitor or VKA initiated within 24 h of randomization
3
Comparator: standard clinical practice without oral anticoagulation
Either antiplatelet agent or no antithrombotic agents

Follow-up: Annually for up to 3 years until the end of the trial

postal questionnaire to their primary care practitioner and surviving participants who had not
4
withdrawn, to check vital status, medication use, and the occurrence of outcomes
interviewed participants or their carers by telephone if there was no response
 OUTCOME
MEASURES
PRIMARY OUTCOME MEASURES SECONDARY OUTCOME MEASURES

1. The number of participants recruited per site per
month (primary feasibility outcome In the internal
feasibility phase)
2. Recurrent symptomatic spontaneous intracranial
hemorrhage (primary clinical outcome in the safety
phase of the trial)
1. Symptomatic major vascular events
a. ischemic stroke, myocardial infarction, sudden cardiac death,
death from another vascular cause, or death of an unknown
cause, major hemorrhagic events
2. Individual types of fatal events
a. vascular deaths [within 30 days of outcome events or from
another vascular cause], sudden cardiac deaths, deaths of an
unknown cause, or deaths from a non-vascular cause
3. Annual ratings of participant dependence and quality of life
Results
 It would be feasible for a 6-year definitive main phase
trial at 60 sites to recruit 800 participants and follow
them for 1 year

Found no evidence that starting oral anticoagulation

Summary of was non-inferior to avoiding oral anticoagulation with

respect to intracranial hemorrhage

results Found weak evidence that starting oral

anticoagulation might be superior to avoiding oral
anticoagulation for preventing any symptomatic
major ischaemic or haemorrhagic vascular event
Thank you