Trial to Evaluate Anticoagulation Therapy in Hemodialysis Patients With Atrial Fibrillation


About this study

This is a prospective, randomized, open-label, blinded end-point evaluation trial. The patient population consists of patients on hemodialysis who have atrial fibrillation (AF) and end-stage renal disease (ESRD) .

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Males and females, age at least 18 years, or the local age of consent, whichever is greater.
  • Patients with AF defined as AF on ECG at enrollment or two or more reports of AF from separate monitoring events at least 2 weeks apart (report of ECG, Holter monitor, event monitor or implantable loop recorder).
  • CHA2DS2-VASc score of ≥ 2.
  • End-stage renal disease treated with hemodialysis for ≥ 3 months.
  • Considered by the treating physician(s) to be candidate for oral anticoagulation.
  • If of childbearing potential, be willing to avoid pregnancy during the study.

Exclusion Criteria:

  • Not considered by the treating physician(s) to be candidates for oral anticoagulation (for example, hemoglobin < 8.5g/dL, history of intracranial hemorrhage, active bleeding, recent gastrointestinal bleed or retroperitoneal bleed, severe hepatic impairment, or anaphylactic reaction to apixaban)
  • Moderate or severe mitral stenosis
  • Conditions other than AF that require anticoagulation such as mechanical prosthetic valve, deep venous thrombosis, or pulmonary embolism
  • Need for aspirin at a dose > 81 mg a day or need for P2Y12 antagonist therapy (for example clopidogrel, prasugrel, or ticagrelor)
  • Life expectancy < 3 months
  • Anticipated kidney transplant within the next 3 months
  • Prisoners or others who are involuntarily incarcerated or detained
  • Pregnant, breastfeeding, or considering pregnancy.
  • Participation in a clinical trial of an experimental treatment within the past 30 days

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Amy Williams, M.D.

Closed for enrollment

More information


  • Dabigatran and rivaroxaban are new oral anticoagulants that are eliminated through the kidneys. Their use in dialysis patients is discouraged because these drugs can bioaccumulate to precipitate inadvertent bleeding. We wanted to determine whether prescription of dabigatran or rivaroxaban was occurring in the dialysis population and whether these practices were safe. Read More on PubMed
  • To determine whether a single-item self-report medication adherence question predicts hospitalisation and death in patients with heart failure. Read More on PubMed
  • The risk of stroke in patients with atrial fibrillation (AF) increases with age. In the ARISTOTLE trial, apixaban when compared with warfarin reduced the rate of stroke, death, and bleeding. We evaluated these outcomes in relation to patient age. Read More on PubMed
  • Current observational studies on warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation (AF) undergoing dialysis found conflicting results. Read More on PubMed
  • To assess the validity of self-report measures of diabetes medication adherence and evaluate the effect of depression on the validity of these reports. Read More on PubMed
  • Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is characterized by vascular calcification, thrombosis and intense inflammation. Prior research has shown that statins have anticalcification, antithrombotic and antiinflammatory properties; however, the association between statin use and CUA has not been investigated. Read More on PubMed
  • Atrial fibrillation (AF) is common among patients with impaired renal function. Apixaban, a novel oral anticoagulant with partial renal excretion, was compared with warfarin and reduced the rate stroke, death and bleeding in the ARISTOTLE trial. We evaluated these outcomes in relation to renal function. Read More on PubMed
  • Both atrial fibrillation and chronic kidney disease increase the risk of stroke and systemic thromboembolism. However, these risks, and the effects of antithrombotic treatment, have not been thoroughly investigated in patients with both conditions. Read More on PubMed
  • Although generally recommended in atrial fibrillation (AF) patients, the effectiveness and safety of oral anticoagulation in dialysis patients with AF is unknown. Read More on PubMed
  • The efficacy of adjusted-dose warfarin for prevention of stroke in atrial fibrillation patients with stage 3 chronic kidney disease (CKD) is unknown. Read More on PubMed
  • Patients with non-valvular atrial fibrillation (AF) and renal insufficiency are at increased risk for ischaemic stroke and bleeding during anticoagulation. Rivaroxaban, an oral, direct factor Xa inhibitor metabolized predominantly by the liver, preserves the benefit of warfarin for stroke prevention while causing fewer intracranial and fatal haemorrhages. Read More on PubMed
  • Cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD) is high, and the presence of CKD worsens outcomes of cardiovascular disease (CVD). CKD is associated with specific risk factors. Emerging evidence indicates that the pathology and manifestation of CVD differ in the presence of CKD. During a clinical update conference convened by the Kidney Disease: Improving Global Outcomes (KDIGO), an international group of experts defined the current state of knowledge and the implications for patient care in important topic areas, including coronary artery disease and myocardial infarction, congestive heart failure, cerebrovascular disease, atrial fibrillation, peripheral arterial disease, and sudden cardiac death. Although optimal strategies for prevention, diagnosis, and management of these complications likely should be modified in the presence of CKD, the evidence base for decision making is limited. Trials targeting CVD in patients with CKD have a large potential to improve outcomes. Read More on PubMed
  • Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. Read More on PubMed
  • Vitamin K antagonists have been shown to prevent stroke in patients with atrial fibrillation. However, many patients are not suitable candidates for or are unwilling to receive vitamin K antagonist therapy, and these patients have a high risk of stroke. Apixaban, a novel factor Xa inhibitor, may be an alternative treatment for such patients. Read More on PubMed
  • Warfarin is commonly used to prevent stroke in patients with atrial fibrillation; however, patients on haemodialysis may not derive the same benefit from warfarin as the general population. There are no randomized controlled studies in dialysis patients which demonstrate the efficacy of warfarin in preventing stroke. In fact, warfarin places the dialysis patient at increased risk for haemorrhagic stroke and possibly ischaemic stroke. Additionally, warfarin increases the risk of major bleeding and has been associated with vascular calcification. Routine use of warfarin in dialysis for stroke prevention should be discouraged, and therapy should only be reserved for dialysis patients at high risk for thrombo-embolic stroke and carefully monitored if implemented. Read More on PubMed
  • Using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS), we determined incidence, prevalence, and outcomes among hemodialysis patients with atrial fibrillation. Cox proportional hazards models, to identify associations with newly diagnosed atrial fibrillation and clinical outcomes, were stratified by country and study phase and adjusted for descriptive characteristics and comorbidities. Of 17,513 randomly sampled patients, 2188 had preexisting atrial fibrillation, with wide variation in prevalence across countries. Advanced age, non-black race, higher facility mean dialysate calcium, prosthetic heart valves, and valvular heart disease were associated with higher risk of new atrial fibrillation. Atrial fibrillation at study enrollment was positively associated with all-cause mortality and stroke. The CHADS2 score identified approximately equal-size groups of hemodialysis patients with atrial fibrillation with low (less than 2) and higher risk (more than 4) for subsequent strokes on a per 100 patient-year basis. Among patients with atrial fibrillation, warfarin use was associated with a significantly higher stroke risk, particularly in those over 75 years of age. Our study shows that atrial fibrillation is common and associated with elevated risk of adverse clinical outcomes, and this risk is even higher among elderly patients prescribed warfarin. The effectiveness and safety of warfarin in hemodialysis patients require additional investigation. Read More on PubMed
  • Use of warfarin, clopidogrel, or aspirin associates with mortality among patients with ESRD, but the risk-benefit ratio may depend on underlying comorbidities. Here, we investigated the association between these medications and new stroke, mortality, and hospitalization in a retrospective cohort analysis of 1671 incident hemodialysis patients with preexisting atrial fibrillation. We followed patient outcomes from the time of initiation of dialysis for an average of 1.6 yr. Compared with nonuse, warfarin use associated with a significantly increased risk for new stroke (hazard ratio 1.93; 95% confidence interval 1.29 to 2.90); clopidogrel or aspirin use did not associate with increased risk for new stroke. Analysis using international normalized ratio (INR) suggested a dose-response relationship between the degree of anticoagulation and new stroke in patients on warfarin (P = 0.02 for trend). Warfarin users who received no INR monitoring in the first 90 d of dialysis had the highest risk for stroke compared with nonusers (hazard ratio 2.79; 95% confidence interval 1.65 to 4.70). Warfarin use did not associate with statistically significant increases in all-cause mortality or hospitalization. In conclusion, warfarin use among patients with both ESRD and atrial fibrillation associates with an increased risk for stroke. The risk is greatest in warfarin users who do not receive in-facility INR monitoring. Read More on PubMed
  • Patients with chronic kidney disease (CKD) have an increased risk for cardiovascular morbidity and mortality. Little attention has been paid to the problem of atrial fibrillation, although this arrhythmia is very frequent with a prevalence of 13 to 27% in patients on long-term hemodialysis. Because of the large number of pathophysiologic mechanisms involved, these patients have a high risk for both thromboembolic events and hemorrhagic complications. Stroke is a frequent complication in CKD: The US Renal Data System reports an incidence of 15.1% in hemodialysis patients compared with 9.6% in patients with other stages of CKD and 2.6% in a control cohort without CKD. The 2-yr mortality rates after stroke in these subgroups were 74, 55, and 28%, respectively. Although oral coumadin is the treatment of choice for atrial fibrillation, its use in patients with CKD is reported only in limited studies, all in hemodialysis patients, and is associated with a markedly increased rate of bleeding compared with patients without CKD. With regard to the high risk for stroke and the conflicting data about oral anticoagulation, an individualized stratification algorithm is presented based on relevant studies. Read More on PubMed
  • Despite common use of warfarin, the bleeding risk associated with this treatment in hemodialysis (HD) patients is unknown. Read More on PubMed
  • Atrial fibrillation is a strong independent risk factor for stroke. Read More on PubMed
  • When it is required to establish a materially significant difference between two treatments, or, alternatively, to show that two treatments are equivalent, standard test statistics and sample size formulae based on a null hypothesis of no difference no longer apply. This paper reviews some of the test statistics and sample size formulae proposed for comparative binomial trials when the null hypothesis is of a specified non-zero difference or non-unity relative risk. Methods based on restricted maximum likelihood estimation are recommended and applied to studies of pertussis vaccine. Read More on PubMed

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