Preserving kidney function in patients with atrial fibrillation: What do the new data say?
How would you consider approaching the treatment of the following patient case?
- Adrian is 77 years old and has been living alone since his wife died 12 years ago
- He avidly follows sports news and often spends time angling in local rivers
- Adrian was diagnosed with atrial fibrillation (AF) 5 years ago after complaining about dizziness and being short of breath; he was prescribed warfarin for protection against stroke
- His kidney function was normal for his age, with an estimated glomerular filtration rate (eGFR) of 73 ml/min/1.73 m2; however, his doctor has found signs of a decline in his kidney function during routine check-ups over the last 2 years
Adrian needs oral anticoagulant (OAC) therapy to protect him from stroke, but can the choice of OAC help to protect his kidneys by slowing the rate of kidney function decline?
Kidney function is an important consideration for stroke prevention in patients with atrial fibrillation
AF is associated with an 80% increased risk of kidney function decline, even in patients who do not yet have abnormal kidney function.1 It is important to preserve kidney function in all patients with AF because kidney function rarely recovers after it declines.2 Furthermore, the risk of both stroke and bleeding in patients with AF increases with decreasing levels of eGFR, complicating their management.
The Niigata preventive medicine study highlighted a bidirectional link between AF and CKD1
AF, atrial fibrillation; CKD, chronic kidney disease
Patients with AF need the protection from stroke that OAC therapy can provide, and the choice of OAC may help slow the rate of kidney function decline in patients with kidney disease.3-5 Geriatrician and stroke specialist Dr Rónán Collins explains in this Thrombosis Adviser podcast: ‘Of all the patients attending the [interdisciplinary atrial fibrillation] clinic, those with reduced creatinine clearances are the people that we need to particularly focus on as we go forward.’
Further data show lower risk of adverse kidney outcomes in patients with non-valvular atrial fibrillation and preserved kidney function treated with rivaroxaban versus warfarin
The 2019 American Heart Association/American College of Cardiology/Heart Rhythm Society guidelines noted that: ‘Over time, NOACs [non-vitamin K antagonist oral anticoagulants] (particularly dabigatran and rivaroxaban) may be associated with lower risks of adverse renal outcomes than warfarin in patients with AF.’5 This guidance is based on real-world observational data.5,6 For example, an analysis of patients with non-valvular AF (NVAF) in a large US administrative database showed significant reductions in the doubling of serum creatinine and ≥30% decline in eGFR with rivaroxaban compared with warfarin.6 Further data from real-world studies continue to add to the evidence supporting the role of non-vitamin K antagonist OACs in preserving kidney function in patients with AF compared with warfarin.7-9 The ANTENNA study adds to the growing evidence of kidney function preservation with rivaroxaban versus warfarin in patients with AF who do not yet have abnormal kidney function.9
ANTENNA was a population-based cohort study that used data from the IQVIA Medical Research Data-UK (IMRD-UK) database of primary electronic health records, covering approximately 6% of the UK population.9,10 The study aimed to determine the incidence of adverse kidney outcomes in 11,652 patients with NVAF and preserved kidney function (eGFR ≥50 ml/min/1.73 m2) receiving rivaroxaban 20 mg once daily (n=5338) or warfarin (n=6314).9 Approximately 1 in 5 patients had diabetes and 1 in 10 patients had heart failure, reflecting the daily challenges of managing patients with co-morbidities in clinical practice.9
Risk of adverse kidney outcomes in patients with NVAF receiving rivaroxaban compared with those receiving warfarin in the ANTENNA study9
CI, confidence interval; eGFR, estimated glomerular filtration rate; HR, hazard ratio; NVAF, non-valvular atrial fibrillation; RRR, relative risk reduction
Patients with NVAF and preserved kidney function receiving rivaroxaban versus warfarin had significantly lower rates of adverse kidney outcomes, including a significant 37% reduction in the rate of serum creatinine doubling and a 24% reduction in the rate of ≥30% decline in eGFR.9 Furthermore, the rate of eGFR decline was significantly reduced in patients receiving rivaroxaban compared with those receiving warfarin (p=0.03).9 These data support improved preservation of renal function with rivaroxaban compared with warfarin in patients with NVAF and preserved kidney function.9
Results from the ANTENNA study strengthen confidence in rivaroxaban for patients at risk of kidney function decline
The ANTENNA study reaffirms previous retrospective studies, which have also shown a reduction in the risk of adverse kidney outcomes in patients with AF receiving rivaroxaban versus a vitamin K antagonist.6-8
The preservation of kidney function with rivaroxaban versus vitamin K antagonists has also been observed in patients who already have kidney disease, suggesting consistent benefit in patients who need it the most. A subanalysis of the retrospective, observational RELOADED study of German claims data showed a 73% lower rate of end-stage renal disease with rivaroxaban versus phenprocoumon in patients with AF and kidney impairment.7
Similar data also exist for patients with AF and diabetes, 8 for whom it is vital to consider the kidneys given that chronic kidney disease is a frequent complication of diabetes.11 In this population, the RIVA-DM study found that rivaroxaban versus warfarin was associated with 19% lower risk of dialysis or kidney transplant (hazard ratio=0.81; 95% confidence interval 0.72–0.90).8 Further information about kidney outcomes with rivaroxaban versus vitamin K antagonists can be found here.
In a recent podcast, Dr Christian Ruff highlighted the importance of kidney function and that safety in patients with AF goes beyond bleeding: ‘Not only do I want to prevent [patients with AF] from stroke and limit their bleeding risk, but I want to protect their kidneys because going on dialysis is a huge life-changing event for these patients.’ Real-world evidence from the ANTENNA study helps to boost confidence that rivaroxaban may help to achieve this goal.
Although bleeding outcomes were not reported in the ANTENNA study, the safety of rivaroxaban was evaluated in both RELOADED and RIVA-DM.7,12 RIVA-DM found that major plus clinically relevant non-major bleeding and critical organ bleeding were significantly reduced in patients taking rivaroxaban compared with warfarin,12 whereas RELOADED reported that the rate of fatal bleeding was significantly lower in patients taking rivaroxaban compared with those on warfarin, and the rate of intracranial haemorrhage was lower with rivaroxaban, but not significantly so.7
Conclusions
Patients with NVAF and preserved kidney function, such as Adrian, need OAC therapy that can protect them from stroke while preserving their kidney function. Data from the ANTENNA study shows lower rates of adverse kidney outcomes and slower rate of eGFR decline with rivaroxaban versus warfarin in patients with NVAF and preserved kidney function. These results increase the weight of evidence with rivaroxaban in patients at risk of kidney function decline and provide reassurance that it may be possible to prevent stroke while protecting the kidneys.
Xarelto is to be used with caution in patients with severe renal impairment (creatinine clearance 15–29 ml/min). Use is not recommended in patients with creatinine clearance <15 ml/min”13
References
- Watanabe H, Watanabe T, Sasaki S et al. Close bidirectional relationship between chronic kidney disease and atrial fibrillation: The Niigata preventive medicine study. Am Heart J 2009;158:629–636. Return to content
- Weis L, Metzger M, Haymann JP et al. Renal function can improve at any stage of chronic kidney disease. PLoS One 2013;8:e81835. Return to content
- Steffel J, Collins R, Antz M et al. 2021 European Heart Rhythm Association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Europace 2021: doi:10.1093/europace/euab065:euab065. Return to content
- Hindricks G, Potpara T, Dagres N et al. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J 2021;42:373–498. Return to content
- January CT, Wann LS, Calkins H et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in collaboration with the Society of Thoracic Surgeons. Circulation 2019;140:e125–e151. Return to content
- Yao X, Tangri N, Gersh B et al. Renal outcomes in anticoagulated patients with atrial fibrillation. Am J Cardiol 2017;70:2621–2632. Return to content
- Bonnemeier H, Kreutz R, Kloss S et al. Comparative safety and effectiveness of non-vitamin-K oral anticoagulants vs phenprocoumon in patients with non-valvular atrial fibrillation and renal disease - Results from the RELOADED study. Eur Stroke J 2019;4:1–860. Abstract AS25-066. Return to content
- Costa O, Brescia CW, Vardar B et al. Kidney, limb and ophthalmic complications and death in patients with nonvalvular atrial fibrillation and type 2 diabetes prescribed rivaroxaban or warfarin: an electronic health record analysis. EP Europace 2021;23:euab116.269. Return to content
- González-Pérez A, Balabanova Y, Sáez ME et al. Renal decline in patients with atrial fibrillation treated with rivaroxaban or warfarin. European Society of Cardiology Congress.Virtual, 27–30 August 2021. Poster Available at: https://esc2021-abstract.medicalcongress.online/mediatheque/media.aspx?channel=103467&mediaId=104597 [accessed 5 November 2021]. González-Pérez A, Balabanova Y, Sáez ME et al. Renal decline in patients with atrial fibrillation treated with rivaroxaban or warfarin. European Society of Cardiology Congress.Virtual, 27–30 August 2021. Poster Available at: https://esc2021-abstract.medicalcongress.online/mediatheque/media.aspx?channel=103467&mediaId=104597 [accessed 5 November 2021]. Return to content
- Candore G, Hedenmalm K, Slattery J et al. Can we rely on results from IQVIA Medical Research Data UK converted to the Observational Medical Outcome Partnership common data model?: A validation study based on prescribing codeine in children. Clin Pharmacol Ther 2020;107:915–925. Return to content
- Gheith O, Farouk N, Nampoory N et al. Diabetic kidney disease: world wide difference of prevalence and risk factors. J Nephropharmacol 2016;5:49–56. Return to content
- Coleman CI, Costa OS, Brescia CW et al. Thromboembolism, bleeding and vascular death in nonvalvular atrial fibrillation patients with type 2 diabetes receiving rivaroxaban or warfarin. Cardiovascular diabetology 2021;20:52. Return to content
- Bayer AG. Xarelto (rivaroxaban) Summary of Product Characteristics. 2021. Available at: https://www.ema.europa.eu/documents/product-information/xarelto-epar-product-information_en.pdf [accessed 6 October 2021] Bayer AG. Xarelto (rivaroxaban) Summary of Product Characteristics. 2021. Available at: https://www.ema.europa.eu/documents/product-information/xarelto-epar-product-information_en.pdf [accessed 6 October 2021] Return to content
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Updated date 10/10/2022
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