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Patients with Worsening Renal Function

This section looks at the epidemiology of renal decline in patients with atrial fibrillation and examines how worsening renal function affects prognosis and treatment.

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Worsening renal function in a patient with atrial fibrillation and diabetes
Follow the story of a patient with atrial fibrillation as they develop diabetes and renal impairment
Approval number: PP-XAR-ALL-1650-1

Worsening renal function is of particular concern in patients with atrial fibrillation (AF), because renal impairment increases the likelihood of a devastating thrombotic event.1-3 More information on the effect of renal function impairment in patients with AF can be found here.
Even more concerning is the fact that AF increases the risk of developing renal dysfunction, making patients with AF more likely to suffer the life-changing effects of worsening renal function.4,5
Unfortunately, once a patient has renal dysfunction, it is likely to get worse if they also have AF. Patients with AF and chronic kidney disease (CKD) were shown to be over 3 times more likely to progress to end-stage renal disease compared with those without AF (adjusted hazard ratio [HR]=3.2; 95% confidence interval [CI] 1.9–5.2).6

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The effect of incident AF on patients with CKD progressing to ESRD.6

To further complicate the picture and emphasize the need to consider renal function, it should be noted that patients with AF who are treated with anticoagulants might be at risk of suffering from an accelerated rate of renal decline due to anticoagulation-related nephropathy (ARN).7 ARN, which includes specific outcomes such as acute kidney injury (AKI), is a commonly undiagnosed side effect of anticoagulation therapy and is associated with an increased risk of renal dysfunction and all-cause mortality.8 Most investigations into ARN have been almost exclusively focussed on vitamin K antagonists (VKAs); however, there have been some recent case reports and animal studies investigating ARN associated with non-vitamin K antagonist oral anticoagulant (NOAC) use.7,8

 

Factoring in diabetes

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Renal function declines at twice the rate in people with diabetes than in people without diabetes.9

Approximately 3 out of 10 patients with AF also have diabetes.10 When present in patients with AF, diabetes is especially serious and should be considered in all treatment decisions. Not only does diabetes increase a patient’s risk of stroke by 1.7-fold, it is also a major risk factor for renal function decline. Alarmingly, renal function declines at twice the rate in people with diabetes than in people without diabetes.9,11
With diabetes leading to both an increased risk of stroke and renal impairment in patients with AF, the presence of co-morbid diabetes is a significant variable to take into account when managing these high-risk patients. More information about diabetes in patients with AF can be found here.

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Overlapping co-morbidities put patients with AF at an even higher risk of stroke.12-14

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Renal outcomes with NOACs compared with warfarin in patients with AF.15

In a sensitivity analysis, rivaroxaban and dabigatran significantly lowered the risks of a ≥30% decline in estimated glomerular filtration rate (eGFR) and of AKI compared with warfarin in patients with AF.
Importantly, the beneficial renal outcomes associated with NOACs were also evident in patients with AF and diabetes, who were less likely to have a ≥30% decline in eGFR or AKI if they received rivaroxaban or dabigatran instead of warfarin.
Moreover, rivaroxaban was the only NOAC shown to reduce the risk of a patient experiencing a doubling of serum creatinine compared with warfarin.15

 

US MarketScan

A study analysed US MarketScan claims data from patients with AF who were oral anticoagulant-naïve ≥12 months prior to being initiated on rivaroxaban (n=36,318) or warfarin (n=36,281).16,17 Patients treated with rivaroxaban were less likely to suffer from AKI, progress to CKD stage V or need dialysis compared with patients receiving warfarin.16,17

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Renal outcomes in patients with AF using US MarketScan claims data in a retrospective study.16,17

CALLIPER

The CALLIPER study analysed claims data from US patients with AF who were either warfarin- or rivaroxaban-naïve and had already been diagnosed with CKD stage III or IV. The study included 1466 patients initiated with a reduced dose of rivaroxaban (15 mg once daily) and 5906 patients who received warfarin. Compared with warfarin, rivaroxaban was associated with a significant 47% reduction in the risk of worsening renal function (HR=0.53; 95% CI 0.35–0.78). Furthermore, in a subanalysis of the approximately 50% of patients with co-morbid diabetes, rivaroxaban was shown to be associated with a significant 50% reduction in the risk of renal decline compared with warfarin (HR=0.50; 95% CI 0.30–0.83).18

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Renal outcomes in patients with AF and renal disease in the CALLIPER study.18

RELOADED

The RELOADED study analysed German claims data from patients with AF and renal disease initiating on rivaroxaban (n=5121), apixaban (n=4750), edoxaban (n=682) or the VKA phenprocoumon (n=7289).19 In patients with existing renal disease, rivaroxaban and apixaban were associated with a beneficial effect on renal outcomes compared with phenprocoumon. Sufficient data were not available to conduct the full analysis for edoxaban.19

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Outcomes in patients with AF and renal disease in the RELOADED study.19

European and American guidelines recommend the use of NOACs over VKAs to reduce the risk of stroke in patients with AF (unless patients are at low risk for stroke [using the CHA2DS2-VASc score] or have true contraindications for anticoagulant therapy).20,21 More information on guidelines in patients with renal impairment and AF can be found here.
In light of the evidence supporting the effects of NOACs on preserving renal function, the 2019 American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines mention that NOACs – particularly dabigatran and rivaroxaban – are associated with reduced risks of adverse renal outcomes over the time periods they were compared with VKAs.20
Furthermore, to account for varying degrees of renal dysfunction and the likelihood of renal decline, both the American College of Cardiology/American Heart Association/Heart Rhythm Society and the European Society of Cardiology guidelinesrecommend regular assessment of renal function by serum creatinine or creatinine clearance in all patients with AF to determine the dosing of therapy and to detect possible CKD.20,21 It is recommended that renal function should be evaluated prior to the initiation of NOACs and at least annually thereafter.20,21

 

For a short summary of why kidney function matters in patients with AF, read our newsletter here.

References

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