Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation

A Controlled, Randomized, Parallel, Multicentre Study to Assess Safety and Tolerability of the Oral Direct Thrombin Inhibitor AZD0837, Given as an Extended-release Formulation, in the Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation

The main purpose of this study is to provide dose-guiding information by assessing the safety and tolerability of 4 different dosing regimens of an extended-release (ER) formulation of AZD0837 compared with well-controlled, dose-adjusted Vitamin-K antagonists (VKA) (aiming for an international normalized ratio (INR) 2.0 to 3.0) in patients with non-valvular atrial fibrillation (AF) with one or more additional risk factors for stroke.

Inclusion Criteria:

• Nonvalvular AF (NVAF) verified by at least two ECGs in the last year separated by at least one week.
• Previous cerebral ischemic attack (stroke or TIA, >30 days prior to randomization)
• Previous systemic embolism.
• Symptomatic congestive heart failure (CHF)
• Impaired left ventricular systolic function
• Diabetes mellitus
• Hypertension requiring anti-hypertensive treatment.

Exclusion Criteria:

• AF secondary to reversible disorders, eg hyperthyroidism, drugs and pulmonary embolism
• Known contraindication to VKA treatment
• Presence of a valvular heart disease, mechanical heart valves, active endocarditis, left ventricular aneurysm or thrombus, atrial myxoma or any condition other than AF requiring chronic anticoagulation treatment
• Conditions associated with increased risk of major bleeding for example: history of intracranial bleeding, history of bleeding gastrointestinal disorder or major surgical procedure or trauma two weeks prior to randomization