Background and Rationale

Patients with chronic kidney disease (CKD) suffer from a high cardiovascular morbidity and mortality. Moreover, their number is dramatically increasing. This is due to several causes, especially to the increasing prevalence of diabetes, hypertension, and in general a higher number of elderly people.

Although about 6 million people suffer from CKD in Germany, only 120,000 are alive in CKD stage 4 and 85,000 in stage 5 (=end-stage kidney disease (ESKD) on peritoneal or hemodialysis). The reason for this phenomenon is the deleterious mortality in the advanced CKD stages 4 and 5.

In contrast, only little attention has yet been paid to the problem of atrial fibrillation (AF) in patients with CKD, although this arrhythmia is very frequent in this cohort due to the high prevalence of structural heart disease and hypertension as the major risk factors.

Patients with CKD suffer from a high risk of both thromboembolic events and bleedings. Concordantly, ischemic (and hemorrhagic) stroke is a typical and frequent complication in ESKD. So far, there is   no evidence-based treatment for patients with ESKD on hemodialysis and thus, there is a need for anticoagulation especially for these high morbid patients.

Apixaban is a novel, potent, oral anticoagulans, belonging to the group of non-vitamin-K anticoagulants, with a low renal clearance (<30% of total clearance). Therefore, apixaban may offer a safe and effective alternative to VKA for this special patient collective.

Thus, the primary goal of the present AXADIA trial is to assess the safety of two types of oral anticoagulants in patients with ESKD on hemodialysis with non-valvular atrial fibrillation (NVAF). The novel FXa inhibitor apixaban (at a reduced dose of 2x 2.5 mg/day) will be compared to the vitamin-K antagonist (VKA) phenprocoumon (target range: International Normalized Ratio (INR) 2.0-3.0) regarding bleeding rates during chronic administration for prevention of stroke or systemic embolism.

The primary hypothesis of the AXADIA study is that oral anticoagulation with apixaban will improve the safety by significantly reducing bleeding rates in patients with ESKD on hemodialysis and NVAF compared to the VKA phenprocoumon.