Please select the eligibility criteria that correspond to the clinical trial below.
Title: Interventional Left Atrial Appendage Closure vs. Novel Anticoagulation Agents in High-risk Patients With Atrial Fibrillation (PRAGUE-17 Study)
Brief Summary: Atrial fibrillation (AF) is the most common cardiac arrhythmia with a prevalence of 1-2%. Without antithrombotic treatment, the annual risk of a cardioembolic event is 5-6%. The source of a cardioembolic event is a thrombus, which usually forms in the left atrial appendage (LAA). The prevention of cardioembolic events involves treatment with anticoagulant drugs, which were limited to, until recently, vitamin K antagonists (e.g. warfarin). Anticoagulant treatment with warfarin can lead to adverse bleeding events, some of which can be life threatening. Recently, two new options for thrombus prevention have been developed. The first is the novel anticoagulants (NOAC), which were associated with slightly better safety profiles due to a lower frequency of intracranial bleeding in large randomized trials . The second option involves interventional occlusion of the LAA. The aim of this project is to compare the LAA occlusion intervention to NOAC pharmacological treatment in a randomized multicenter study of AF patients at high risk of a cardioembolic event.


Options:
A: Inclusion Criteria:

1. history of significant bleeding (i.e. bleeding which required intervention or hospitalization), even in the absence of anticoagulation treatment at the time of the bleeding event, or
2. a cardioembolic event, which occurred on anticoagulation, or
3. a high risk profile of the patient, defined as a CHA2DS2-VASc score ≥ 3 and a HAS-BLED score ≥ 2

Exclusion Criteria:

1. thrombus in the LA or LAA;
2. mechanical valve prosthesis;
3. mitral stenosis;
4. previous LAA ligation during cardiac surgery;
5. life expectancy less than 2 years;
6. comorbidities other than AF, which present an indication for anticoagulation;
7. patent foramen ovale with atrial septal aneurysm
8. mobile plaque in the aorta;
9. symptomatic atherosclerosis of the carotid artery;
10. pericardial effusion greater than 10 mm;
11. clinically significant bleeding within the 30 days prior to the scheduled procedure;
12. stroke or other cardioembolic event within the 30 days prior to the scheduled procedure;
13. acute coronary syndrome within the 90 days prior to the scheduled procedure,
14. gravidity,
15. significant valvular disease,
16. creatinine clearance less than 30 ml/min
B: Inclusion Criteria:

1. Written informed consent provided
2. Age ≥45 years, at the time of signing the informed consent
3. Previous intracranial hemorrhage (symptomatic, spontaneous and non-traumatic non-lobar intraparenchymal or intraventricular hemorrhage, and symptomatic spontaneous or non-penetrating traumatic subdural hemorrhages) on or off antithrombotic therapy
4. Documented atrial fibrillation (paroxysmal, persistent, permanent)
5. CHA2DS2-VASc score ≥2

Exclusion Criteria:

1. Recent intracranial hemorrhage (within 14 days)
2. Secondary macrovascular, neoplastic or infectious causes of intracranial hemorrhage (except for antithrombotic treatment or non-penetrating traumatic subdural hemorrhages)
3. Isolated subarachnoid hemorrhage (convexity or basal); subarachnoid blood tracking onto convexity secondary to an intraventricular hemorrhage or as part of a multicompartment bleed in cases of traumatic subdural hemorrhages are eligible
4. Need for ongoing oral anticoagulant therapy for indication other than AF (e.g. mechanical heart valve, venous thromboembolic disease)
5. Need for ongoing antiplatelet therapy for indication where edoxaban would not be a suitable substitute
6. Plans for left atrial appendage occlusion
7. Estimated creatinine clearance (CrCl) \< 15 mL/min
8. Platelet count less than 100,000mm3 at enrollment or other bleeding diathesis
9. Persistent, uncontrolled hypertension (systolic BP averaging \>150 mmHg)
10. Chronic use of NSAID
11. Clinically significant active bleeding, including gastrointestinal bleeding
12. Lesions or conditions at increased risk of clinically significant bleeding, e.g. active peptic ulcer disease with recent bleeding, patients with spontaneous or acquired impairment of hemostasis
13. Antiphospholipid antibody syndrome
14. Hepatic disease associated with coagulopathy and clinically relevant bleeding risk
15. Known hypersensitivity to edoxaban
16. Estimated inability to adhere to study procedures
17. Pregnancy or breastfeeding
18. Estimated life expectancy \< 6 months at the time of enrollment
19. Close affiliation with the investigational site; e.g. a close relative for the investigator, dependent person (e.g., employee or student of the investigational site)
20. Lobar intraparenchymal hemorrhage

    * Post menopausal female subjects must be amenorrheic for ≥12 months prior to screening or ≥6 weeks post-surgical bilateral oophorectomy (with or without hysterectomy) prior to screening. Women of childbearing potential must have negative serum pregnancy test within 7 days prior to randomization or urine pregnancy testing within 24 hours of randomization. Heterosexually active women of childbearing potential must use highly effective methods of contraception for 32 days after discontinuation (duration of study drug plus 30 days duration of one ovulatory cycle).
C: 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.
D: Inclusion Criteria:

* Intracranial spontaneous hemorrhage on brain CT scan
* Intracranial hemorrhage during treatment with oral anticoagulants
* Bedridden patients (item 6 of NIHSS: motor leg points 3 or 4 or severe ataxia for cerebellar hemorrhage).

Exclusion Criteria:

* cerebral hemorrhage due to intracranial vascular malformation
* rebleeding on CT scan after 72 hours from stroke (before randomization)

Answer: A