Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation - RENAL-AF

Dec 14, 2022
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Presenter/Author:
Sean Pokorney, MBA, MD
Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
BMS/Pfizer Alliance
Date Presented:
11/16/2019
Date Published:
11/06/2022
Date Updated:
12/14/2022
Original Posted Date:
11/17/2019
References

Contribution To Literature:

Highlighted text has been updated as of December 13, 2022.

The RENAL-AF trial showed that apixaban 5 mg BID results in similar rates of bleeding and strokes as warfarin among patients with end-stage renal disease on hemodialysis.

Description:

The goal of the trial was to assess the safety and efficacy of apixaban for stroke prophylaxis among patients with atrial fibrillation (AF) and end-stage renal disease on hemodialysis.

Study Design

Eligible patients were randomized in a 1:1 fashion to either apixaban 5 mg BID (29% received 2.5 mg BID) (n = 82) or warfarin with international normalized ratio (INR) goal 2-3 (n = 72). Time in therapeutic range (TTR) for warfarin: 44.3%.

  • Total number of enrollees: 154
  • Duration of follow-up: 1 year
  • Mean patient age: 69 years
  • Percentage female: 35%

Inclusion criteria:

  • AF
  • CHA2DS2-VASc score ≥2
  • End-stage renal disease on hemodialysis
  • Candidate for oral anticoagulant

Exclusion criteria:

  • Moderate or severe mitral stenosis
  • Oral anticoagulant for non-AF indication
  • Need for aspirin >81 mg
  • Need for dual antiplatelet therapy
  • Life-expectancy <3 months

Other salient features/characteristics:

  • Median CHA2DS2-VASc score: 4.0
  • Prior stroke: 19%
  • Prior bleeding: 21%
  • Aspirin: 40%

Principal Findings:

The primary outcome, International Society on Thrombosis and Haemostasis (ISTH) clinically relevant nonmajor bleed at 1 year, for apixaban vs. warfarin, was:  31.5% vs. 25.5% (hazard ratio 1.20, 95% confidence interval 0.63-2.30).

  • Hemodialysis access site bleeding: 13% vs. 8%
  • Intracranial bleeding: 1% vs. 1%
  • Gastrointestinal bleeding: 2% vs. 8%

Secondary outcomes for apixaban vs. warfarin:

  • ISTH major bleed: 8.5% vs. 9.7%
  • Stroke or systemic embolism: 3.0% vs. 3.3% (p > 0.05)
  • Cardiovascular death: 11% vs. 5.6%
  • All-cause mortality: 26% vs. 18%

Within the cohort of 63 patients with pharmacokinetic data, there were 21 patients with major or clinically relevant nonmajor bleeding events and 42 patients without such an event. There was substantial overlap between pharmacokinetic values at steady state of patients with and without a major or clinically relevant nonmajor bleeding event with respect to the minimum apixaban blood concentration, 12-hour area under the curve 0-12, and maximum apixaban blood concentration.

Interpretation:

The results of this trial indicate that apixaban (5 mg BID in 71%, 2.5 mg BID in the remainder) results in similar rates of bleeding and strokes as warfarin among patients with end-stage renal disease on hemodialysis. Some important features of this trial: The trial was stopped early due to loss of funding (originally powered to enroll 760 patients). TTR with warfarin was only approximately 44%, with a large proportion of patients in the subtherapeutic range. It remains unclear if routine use of the lower apixaban dose (2.5 mg BID) and cessation of aspirin (used in ~40%) would have resulted in lower bleeding compared with warfarin.

References:

Pokorney SD, Chertow GM, Al-Khalidi HR, et al. Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial. Circulation 2022;146:1735-45.

Editorial Comment: Benz AP, Eikelboom JW. Bend Apixaban Compared With Warfarin in Patients With Atrial Fibrillation and End-Stage Renal Disease: Lessons Learned. Circulation 2022;146:1746-8.

Presented by Sean D. Pokorney at the American Heart Association Annual Scientific Sessions (AHA 2019), Philadelphia, PA, November 16, 2019.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Prevention, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: AHA19, AHA Annual Scientific Sessions, Anticoagulants, Aspirin, Atrial Fibrillation, Hemorrhage, Hemostasis, Kidney Failure, Chronic, Primary Prevention, Renal Dialysis, Stroke, Thrombosis, Warfarin


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