Strategies for the Management of Atrial Fibrillation in patiEnts Receiving Dialysis 2 (SAFE-D2)

Strategies for the Management of Atrial Fibrillation in patiEnts Receiving Dialysis 2 (SAFE-D2)

People receiving dialysis are more likely to develop atrial fibrillation (AF), an irregular heartbeat that increases the risk of stroke. Blood-thinning medications (anticoagulants) are commonly used to prevent strokes in people with AF, but it is not known whether they are beneficial for people receiving dialysis because this group has not been well represented in previous clinical trials. As a result, healthcare providers do not have clear evidence to guide treatment decisions.

The SAFE-D2 study will compare two approaches to preventing stroke in adults receiving maintenance hemodialysis or peritoneal dialysis who have non-valvular AF and are at increased risk of stroke. Participants will be randomly assigned (by chance) to receive either apixaban, an oral blood thinner, or no oral anticoagulant, while continuing to receive their usual dialysis and medical care.

The main goal of the study is to determine whether apixaban is more effective than no oral anticoagulant at reducing the risk of stroke or blood clots traveling to other parts of the body (systemic embolism). The study will also compare the two approaches with respect to survival, heart-related complications, major bleeding and other bleeding events, hospitalizations, dialysis access complications, quality of life, and the overall balance of benefits and risks.

Approximately 848 participants from Canada, Brazil, and Israel will take part in the study. The results of SAFE-D2 are expected to provide important evidence to help patients, families, and healthcare providers make informed decisions about stroke prevention for people receiving dialysis who have atrial fibrillation.

Inclusion criteria

To be eligible to participate in this trial, participants need to satisfy ALL these inclusion criteria:

1. Age ≥18 years,

2. Kidney failure treated with hemodialysis or peritoneal dialysis for at least 90 days,

3. A history of non-valvular AF or atrial flutter (AFL) defined as one of the following:

   1. AF/AFL on an ECG at enrollment.
   2. ≥2 episodes of AF/AFL on cardiac diagnostics with each episode lasting ≥30 seconds and occurring ≥24 hours apart.
   3. One episode of AF/AFL on cardiac diagnostics lasting ≥30 seconds, plus ≥1 separate documented episode in the medical record.
   4. One episode of AF (reported by cardiac diagnostics or documented in the medical record) plus treatment with an oral anticoagulant for stroke prevention as a result of AF/AFL; or
   5. AF/AFL documented on one occasion in a cardiologist report.

4. Meet the CHA2DS2-VASc criteria (i.e. ≥2 for men and ≥3 for women)

Exclusion Criteria

Potential participants must have NONE of the following exclusion criteria:

1. Mitral stenosis described as moderate or severe.
2. Anticoagulation indicated for a reason other than atrial fibrillation.
3. Receipt of aspirin at a dose of >160 mg daily.
4. Ongoing requirement at screening for a strong CYP3A4/P-gp inhibitor or inducer that cannot be discontinued, substituted, or otherwise managed safely.
5. Ongoing requirement for dual antiplatelet therapy at the time of screening that, in the judgement of the treating clinician, is expected to remain necessary after randomization and cannot be safely de-escalated to single antiplatelet therapy in the event of randomization to apixaban.
6. Known clinically significant coagulopathy, or other bleeding risk that, in the judgment of the treating physician, renders oral anticoagulation unsafe.
7. A major bleeding event in the 30 days prior to study enrollment, or any active and clinically significant bleeding.
8. Current pregnancy or breastfeeding.
9. Anticipated life expectancy < 6 months.
10. A scheduled live donor kidney transplant in the next 6 months.
11. Co-enrollment in a clinical trial where the intervention is deemed to interfere with the adherence, safety or efficacy of the SAFE-D2 treatment strategies
12. The treating clinical team has determined that long-term OAC is clearly indicated such that randomization to the no OAC strategy would not be clinically acceptable.
13. The treating clinical team has determined that long-term OAC is clearly contraindicated such that randomization to the apixaban strategy would not be clinically acceptable.