Replication of the ROCKET-AF Anticoagulant Trial in Healthcare Claims Data

Inclusion Criteria:

• 1. Patients 18 years of age or older
• 2. Non-valvular atrial fibrillation
• 3. Non-valvular atrial fibrillation 14 days or after the previous diagnosis of AF in inclusion 2

• 4. History of prior ischemic stroke, TIA, systemic embolism or two or more of the following risk factors:

     • 4a. Heart failure and/or left ventricular ejection fraction ≤35%
     • 4b. Hypertension (defined as use of antihypertensive medications within 6 months before the screening visit or persistent systolic blood pressure above 140 mmHg or diastolic blood pressure above 90 mmHg)
     • 4c. Patients 75 years of age or older
     • 4d. Diabetes mellitus (defined as a history of type 1 or type 2 diabetes mellitus or use of antidiabetic medications within 6 months before screening visit)

Exclusion Criteria:

• 1. Cardiac-related conditions

     • 1a. Hemodynamically significant mitral valve stenosis
     • 1b. Prosthetic heart valve (annuloplasty with or without prosthetic ring, commissurotomy and/or valvuloplasty are permitted)
     • 1e. Known presence of atrial myxoma or left ventricular thrombus
     • 1f. Active endocarditis

• 2. Hemorrhage-related risk criteria

     • 2a. Active internal bleeding

     • 2b. History of or condition associated with increased bleeding risk including, but not limited to:

       • Major surgical procedure or trauma within 30 days before the randomization visit
       • Clinically significant gastrointestinal bleeding within 6 months before the randomization visit
       • History of intracranial, intraocular, spinal, or atraumatic intra-articular bleeding
       • Chronic hemorrhagic disorder
       • Known intracranial neoplasm, arteriovenous malformation, or aneurysm
     • 2d. Platelet count \< \<90,000/μL at the screening visit
     • 2e. Sustained uncontrolled hypertension: systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥100

• 3. Concomitant conditions and therapies

     • 3a. Severe, disabling stroke (modified Rankin score of 4 to 5, inclusive) within 3 months or any stroke within 14 days before the randomization visit
     • 3b. Transient ischemic attack within 3 days before the randomization visit
     • 3c. Indication for anticoagulant therapy for a condition other than atrial fibrillation (e.g., VTE)

     • 3d. Treatment with:

       • Aspirin >100 mg daily
       • Aspirin in combination with thienopyridines within 5 days before randomization
       • Intravenous antiplatelets within 5 days before randomization
       • Fibrinolytics within 10 days before randomization
       • Note: Aspirin ≤100 mg monotherapy is allowed and thienopyridine monotherapy is allowed.
     • 3f. Systemic treatment with a strong inhibitor of cytochrome P450 3A4, such as ketoconazole or protease inhibitors, within 4 days before randomization, or planned treatment during the time period of the study
     • 3g. Treatment with a strong inducer of cytochrome P450 3A4, such as rifampin/rifampicin, within 4 days before randomization, or planned treatment during the time period of the study
     • 3h. Anemia (hemoglobin \<10 g/dL) at the screening visit
     • 3i. Pregnancy or breast-feeding
     • 3k. Known HIV infection at time of screening
     • 3l. Calculated CLCR \<30 mL/min at the screening visit (refer to Attachment 4 for calculating CLCR)
     • 3m. Known significant liver disease (e.g., acute clinical hepatitis, chronic active hepatitis, cirrhosis), or ALT >3 x the ULN

• 4. Study participation and follow-up-related criteria

     • 4a. Serious concomitant illness associated with a life expectancy of less than 2 years
     • 4b. Drug addiction or alcohol abuse within 3 years before the randomization visit
     • 4f. Inability or unwillingness to comply with study-related procedures