Please select the eligibility criteria that correspond to the clinical trial below.
Title: Microbleeds and Genetic Risk Factors to Predict the Risk of Intracranial Haemorrhage in Patients Treated With Anticoagulation Following Cardioembolic Stroke Due to Atrial Fibrillation
Brief Summary: Study I: CROMIS-2 (AF) Prospective cohort study of patients anticoagulated after cardioembolic stroke An observational inception cohort study (n=1425) of patients throughout the United Kingdom (UK) - (79 hospitals) started on best practice oral anticoagulant (without prior use) for presumed cardioembolic ischaemic stroke due to non-valvular AF with follow up for the occurrence of intracerebral haemorrhage (ICH) and ischaemic stroke for an average of two years. The main baseline exposures (risk factors of interest) are the presence of cerebral microbleeds (CMBs) on magnetic resonance imaging (MRI), and genetic polymorphisms in candidate genes with potential functional relevance to ICH risk.

Study II: CROMIS-2 (ICH) Observational and genetics study of intracerebral haemorrhage The investigators will also recruit 600 patients admitted to participating centres with ICH (with a target of at least 300 anticoagulant-related ICH cases) and collect DNA to increase the power of the genetic studies. The investigators will collect clinical and imaging data from these ICH cases to investigate risk factors associated with anticoagulant-related ICH compared to non anticoagulant-related ICH.


Options:
A: Inclusion Criteria:

* Patients with transient ischemic attack (TIA) or ischemic stroke within 180 days prior to screening - Adult aged 20 years or older
* High risk of hemorrhagic stroke (history of intracranial hemorrhage or imaging evidence of previous intracranial hemorrhage)
* Informed consent

Exclusion Criteria:

* Clinical diagnosis of myocardial infarction or coronary intervention within 4 weeks
* Bleeding tendency
* Pregnant or breast-feeding woman
* Hemorrhagic stroke within 6 months
* Patient who was taking antithrombotic medication other than aspirin and does not agree to change the previous medication
* Severe cardiovascular disease such as cardiomyopathy or congestive heart failure
* Life expectancy less than one year
* Contraindication to long term aspirin use
* Enrolled in other clinical trial within 30 days
B: Inclusion Criteria:

1. Adults (≥30 years) with spontaneous primary ICH (i.e. without known underlying structural, macrovascular or other cause (e.g. arteriovenous malformation, tumour) after adequate investigation at the discretion of the local investigator). This will include participants presumed to have cerebral SVD (both hypertensive arteriopathy and cerebral amyloid angiopathy)
2. Clinical team opinion that BP control since the ICH is not adequate AND the measured SBP prior to randomisation is ≥130 mm Hg
3. There is no time limit for recruitment; however, recruitment as soon as is practical after the ICH is encouraged. Recruitment at a later stage is acceptable as long as there is evidence of inadequate BP control AND SBP at randomisation is ≥130 mm Hg
4. Ability and willingness to undertake BP measurements,, either unassisted or with the help of a relative, friend or carer: this can be undertaken in any destination after hospital discharge (e.g. home, rehabilitation unit, nursing or care home)
5. Ability and willingness to attend and complete the study assessments including cognitive screen
6. Ability and willingness to provide informed consent, or with a suitable consultee available and able to participate in the intervention (e.g. with a motivated carer)

Exclusion Criteria:

1. Inability to provide informed consent or lack of suitable consultee (if unable to provide personal consent, lack of suitable consultee)
2. Evidence of a macrovascular or structural cause for ICH (e.g. AVM or tumour)
3. Diagnosis of dementia (DSM IV criteria, or self-reported or documented in medical records)
4. Low Functional status (MRS ≥4) before or after ICH or frailty likely to make participation in 1-year follow-up difficult for the participant
5. Life expectancy \<2 years
6. Taking more than 2 BP-lowering medications (i.e. 3 or more) at the time of consent
7. Consistently good BP control (below 130/80 mm Hg on measures taken as part of routine clinical care) prior to planned recruitment, judged not to require more intensive treatment
8. Known flow-restricting intracranial/extracranial large arterial stenosis
9. Known absence of mobile phone coverage from all network operators and home internet at the participant's home
10. Known sensitivity or contra-indication to BP treatments (e.g. symptomatic postural hypotension) is not an absolute exclusion criterion, but more information must be provided
11. Note that participation in other CTIMP or device trial is NOT an automatic exclusion criterion
C: Study I: CROMIS-2 (AF)

Inclusion criteria:

* Adult (≥18y; no upper limit) patients with a clinical diagnosis of non-valvular AF (verified by ECG) with intention to treat with best practice oral anticoagulants (e.g. warfarin)
* Previous ischaemic stroke or TIA diagnosed by treating clinician
* All patients must be able to have GRE MRI before (or within 1 week) of starting best practice oral anticoagulant

Exclusion Criteria:

* Any MRI contraindications
* Previous use of oral anticoagulation
* Definite contra-indication to oral anticoagulation
* Serious head injury (resulting to loss of consciousness)

Study II: CROMIS-2 (ICH)

Inclusion criteria:

• Adult (\>18y) patients treated at participating centres with confirmed ICH (confirmed on CT or MRI scans) with or without a history of anticoagulant use at the time of the ICH

Exclusion criteria:

* Known underlying structural cause for ICH (e.g arteriovenous malformation, tumour, cavernoma, intracranial aneurysm, haemorrhagic transformation of an infarct)
* Major head trauma (causing loss of consciousness and though to be sufficient to have caused the ICH) in previous 24 hours
D: Inclusion Criteria:

* Adults (≥18 years) with a history of primary ICH that is confirmed by imaging (copy of the brain imaging report to be uploaded to the database, labelled with participant identification (ID) and with personal identifiers removed)
* Clinically stable, as judged by investigator
* Average of two resting SBP levels measured 5 minutes apart in the range 130-160mmHg recorded in a seated position (National Heart Foundation of Australia Guidelines). (Patients with higher SBP can be included if considered by attending clinician that management is consistent with local standards of clinical practice)
* Geographical proximity to the recruiting hospital and/or follow-up medical clinic site to allow ready access for in-person clinic visits during follow-up
* No clear contraindication to any of the study treatments
* Provision of written informed consent

Exclusion Criteria:

* Taking an ACE-I that cannot be switched to any of the following alternatives:

  * telmisartan 20 or 40mg, amlodipine 2.5 or 5mg, indapamide 1.25mg, or
  * an equivalent class (ARB, CCB or thiazide \[TZ\]-like diuretic), or
  * a BB
* Contraindication to any of the study medications, in the context of currently prescribed BP-lowering medication
* Unable to complete the study procedures and/or follow-up
* Females of child-bearing age and capability, who are pregnant or breast-feeding, or those of child-bearing age and capability who are not using adequate birth control
* Significant hyperkalaemia and/or hyponatremia, in the opinion of the responsible physician
* Estimated glomerular filtration rate (eGFR) \<30mL/min/1.73m2
* Severe hepatic impairment (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] \>3x the upper limit of normal \[ULN\])
* Any other condition that in the opinion of the responsible physician or investigator renders the patient unsuitable for the study (e.g. severe disability \[i.e. simplified modified Rankin Scale (smRS) of 4-5\] or significant memory or behavioural disorder)

Exclusion Criteria for MRI (as applies)

• Any MRI contraindication (e.g. metallic implants, claustrophobia, etc) or participant refusal.

Answer: C