A Study of Atrial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke

Overview

About this study

The primary purpose of this study is to test the theory that Eliquis (apixaban) is superior to aspirin for the prevention of recurrent stroke in patients with cryptogenic ischemic stroke and atrial cardiopathy.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

Inclusion Criteria:

  •  Age ≥ 45 years old.
  • Clinical diagnosis of ischemic stroke + brain imaging to rule out hemorrhagic stroke.
  • Modified Rankin Scale (MRS) score ≤ 4. 
  • Ability to be randomized within 3 to 120 days after stroke onset.
  • ESUS, defined as all of the following: 
    • Stroke detected by CT or MRI that is not lacunar. Lacunar is defined as a subcortical (this includes pons and midbrain) infarct in the distribution of the small, penetrating cerebral arteries whose largest dimension is ≤1.5 cm on CT or ≤2.0 cm on MRI diffusion images/<1.5 cm on T2 weighted MR images. The following are not considered lacunes: multiple simultaneous small deep infarcts, lateral medullary infarcts, and cerebellar infarcts. Patients with a clinical lacunar stroke syndrome and no infarct on imaging are excluded;
    • Absence of extracranial or intracranial atherosclerosis causing ≥50 percent luminal stenosis of the artery supplying the area of ischemia. Patients must undergo vascular imaging of the extracranial and intracranial vessels using either catheter angiography, CT angiogram (CTA), MR angiogram (MRA), or ultrasound, as considered appropriate by the treating physician and local principal investigator;
    • No major-risk cardioembolic source of embolism, including intracardiac thrombus, mechanical prosthetic cardiac valve, atrial myxoma or other cardiac tumors, mitral stenosis, myocardial infarction within the last 4 weeks, left ventricular ejection fraction <30 percent, valvular vegetations, or infective endocarditis). Patent foramen ovale is not an exclusion. All patients must undergo electrocardiogram, transthoracic or transesophageal echocardiography (TTE or TEE) and at least 24 hours of cardiac rhythm monitoring (Holter monitor or telemetry or equivalent). Additional cardiac imaging, such as cardiac MRI, or cardiac CT will be performed at the discretion of the local treating physician and principal investigator. Additional cardiac rhythm monitoring, such as monitored cardiac outpatient telemetry (MCOT) or an implanted cardiac monitor, will be at the discretion of the treating physician and local principal investigator;
    • No other specific cause of stroke identified, such as arteritis, dissection, migraine, vasospasm, drug abuse, or hypercoagulability. Special testing, such as toxicological screens, serological testing for syphilis, and tests for hypercoagulability, will be performed at the discretion of the treating physician and local principal investigator.

Exclusion Criteria:

  • History of AF, AF on 12-lead ECG, or any AF of any duration during heart-rhythm monitoring prior to randomization. 
  • Clear indication for treatment-dose anticoagulant therapy, such as venous thromboembolism or a mechanical heart valve. 
  • Need for antiplatelet agent, such as aspirin or clopidogrel.
  • History of spontaneous intracranial hemorrhage. 
  • Chronic kidney disease with serum creatinine ≥2.5 mg/dL. 
  • Active hepatitis or hepatic insufficiency with Child-Pugh score B or C. - Clinically significant bleeding diathesis. 
  • Unresolved anemia (hemoglobin <9 g/dL) or thrombocytopenia (<100 x 10E9/L). 
  • Clinically significant gastrointestinal bleeding within the past year (e.g., not due to external hemorrhoids).
  • At risk for pregnancy: premenopausal or postmenopausal woman within 12 months of last menses without a negative pregnancy test or not committing to adequate birth control, which includes an oral contraceptive, two methods of barrier birth control such as condom with or without spermicidal lubricant + diaphragm, or abstinence.
  • Known allergy or intolerance to aspirin or apixaban.
  • Concomitant participation in another clinical trial involving a drug or acute stroke intervention.
  • Considered by the investigator to have a condition that precludes follow-up or safe participation in the trial. 
  • Inability of either participant or surrogate to provide written, informed consent for trial participation.

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Michelle Lin, M.D., M.P.H.

Open for enrollment

Contact information:

Latrice Jones B.S.

127or7833925

Jones.Latrice@mayo.edu

More information

Publications

  • Non-vitamin K antagonist oral anticoagulant (NOAC) drugs are at least equivalent to warfarin for ischemic stroke prevention in patients with atrial fibrillation and have a lower risk of intracranial hemorrhage. The role of these agents in the prevention and treatment of other types of cerebrovascular disease remains unclear. Read More on PubMed
  • Although left atrial enlargement (LAE) increases incident stroke risk, the association with recurrent stroke is less clear. Our aim was to determine the association of LAE with recurrent stroke most likely related to embolism (cryptogenic and cardioembolic) and all ischemic stroke recurrences. Read More on PubMed
  • Atrial fibrillation (AF) has long been associated with a heightened risk of ischemic stroke and systemic thromboembolism, but recent data require a re-evaluation of our understanding of the nature of this relationship. New findings about the temporal connection between AF and stroke, alongside evidence linking markers of left atrial abnormalities with stroke in the absence of apparent AF, suggest that left atrial thromboembolism may occur even without AF. These observations undermine the hypothesis that the dysrhythmia that defines AF is necessary and sufficient to cause thromboembolism. In this commentary, we instead suggest that the substrate for thromboembolism may often be the anatomic and physiological atrial derangements associated with AF. Therefore, our understanding of cardioembolic stroke may be more complete if we shift our representation of its origin from AF to the concept of atrial cardiopathy. Read More on PubMed
  • Because of its association with atrial fibrillation and heart failure, we hypothesized that amino terminal pro-B-type natriuretic peptide (NT-proBNP) would identify a subgroup of patients from the Warfarin-Aspirin Recurrent Stroke Study, diagnosed with inferred noncardioembolic ischemic strokes, where anticoagulation would be more effective than antiplatelet agents in reducing risk of subsequent events. Read More on PubMed

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20461648

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