Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in AF

Prior treatment

• Other indication for antiplatelet therapy or anticoagulation;
• Conditions associated with an increased risk of bleeding described as follows:
  • Major surgery within the previous month;
  • Planned surgery or intervention within the next 3 months;
  • History of intracranial, intraocular, spinal, retroperitoneal or a traumatic intra-articular bleeding;
  • Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days;
  • Haemorrhagic disorder or bleeding diathesis;
  • Fibrinolytic agents within 48 hours of study entry;
  • Recent malignancy or radiation therapy (within 6 months from the time of enrolment) and not expected to survive 3 years;
• Participation in another study involving an investigational drug (under development) at the same time or within 30 days of randomization;

Other illness

• Known diagnosis of dementia;
• Valvular AF [mechanical heart valve, moderate to severe mitral stenosis (rheumatic or non rheumatic), or hypertrophic cardiomyopathy];
• History of GI bleeding;
• Reversible cause of AF (e.g. cardiac surgery, pulmonary embolism, untreated hyperthyroidism);
• Subjects considered unreliable, or having a life expectancy of less than 3 years or having any condition which, in the opinion of the investigator, would not allow safe participation in the study (e.g. drug addiction, alcohol abuse);
• History of allergic reaction to rivaroxaban.
• History of allergic reaction, in the absence of desensitization to acetylsalicylic acid in patients with vascular disease.

Lab values

• Severe renal impairment (creatinine clearance 30 mL/min or less);
• Active liver disease (e.g. acute clinical hepatitis, chronic active hepatitis, cirrhosis), or Alanine Transaminase (ALT) >3 times the upper limit of normal;
• Anemia or thrombocytopenia (according to the normal range values of the local laboratory);

Other

• MMSE score <25;
• Absence of recurrence of AF 3 months after AF ablation;
• Active infective endocarditis;
• Women who are pregnant or of childbearing potential not using a medically acceptable form of contraception throughout the study;
• Women who are breastfeeding;

• Age at consent ≥30 to ≤62 years;
• Non-valvular atrial fibrillation (paroxysmal, persistent or permanent) documented by any electrical tracing or any device (i.e. routine 12-lead electrocardiogram, Holter monitor [continuous ECG recording] rhythm strip, intracardiac electrogram, or pacemaker or implantable cardiac defibrillator interrogation of at least 30 s, transcutaneous monitoring or other) in the last 2 years;
• Low risk of stroke as defined by the absence of all of the following:
  • Prior stroke or Transient Ischemic Attack, ii. Hypertension, iii. Diabetes mellitus, iv. Congestive heart failure (New York Heart Association class II or higher at the time of enrolment or a known left ventricular ejection fraction <35%);
• Signed informed consent
  • For entry into the study, none of the following criteria MUST be met

Criteria the registry did not label

• For entry into the study, the following criteria must be met: