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

Please see: https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV for full code and algorithm definitions. Eligible cohort entry dates: Market availability of rivaroxaban in the U.S. started on November 4, 2011. For Marketscan: November 4, 2011 -Dec 31, 2018 (end of data availability). For Optum: November 4, 2011 -Dec 31, 2019 (end of data availability). For Medicare: November 4, 2011 -Dec 31, 2017 (end of data availability) 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