Renal Decline Slower With Rivaroxaban Than Warfarin in AF Patients

Liam Davenport

August 31, 2021

Patients with non-valvular atrial fibrillation (NVAF) experience fewer adverse renal outcomes and have a slower decline in kidney function if they are given rivaroxaban rather than warfarin, suggests real-world analysis.

Dr Antonio González Pérez, Spanish Centre for Pharmacoepidemiologic Research, Madrid, Spain, and colleagues looked at the impact of oral anticoagulant (OAC) therapy on kidney function in more than 11,600 UK NVAF patients in primary care.

Rivaroxaban was associated with a 37% reduction in the risk of doubling serum creatinine (sCr) levels versus warfarin, as well as a 24% decrease in the likelihood of a reduction in the estimated glomerular filtration rate (eGFR) of 30% or more.

Patients given the drug also experienced a significant reduction in the rate of decline in eGFR during the study period compared with those treated with warfarin.

The research was presented at the European Society of Cardiology Congress (ESC) 2021 on August 27.

Rivaroxaban was associated with a "markedly reduced risk and rate of renal decline" versus warfarin after adjusting for potential confounders, Dr González Pérez said.

"However, as with all observational studies, the possibility of residual confounding cannot be excluded," he added.

'Interesting' Findings

Commenting for the ESC, Michael Böhm, Klinik für Innere Medizin III, Universität des Saarlandes, Homburg, Germany, said that the data are "are interesting and extend previous findings from clinical trials to the real world".

Indeed, the current results fit with an analysis of the RE-LY trial conducted by Professor Böhm and colleagues, which showed that atrial fibrillation patients treated with dabigatran etexilate had a significantly slower rate of decline in renal function than those given warfarin.

He told Medscape News UK, with these and other observational analyses, it is "good to have reassurance that direct oral anticoagulants have a beneficial effect on kidney outcomes".

It is not surprising vitamin K antagonists such as warfarin could have an adverse effect on renal function, as they "inhibit the phosphorylation of vitamin K dependent enzymes" that prevent calcification of blood vessels, Prof Böhm continued.

"Therefore, antagonising this could provide adverse cardiovascular effects."

UK Primary Care Data

With a recent observational study suggesting that renal decline among patients with NVAF could be faster with warfarin versus rivaroxaban, the researchers determined the incidence of adverse renal outcomes in primary care.

They collated electronic health records from the IQVIA Medical Research Data repository of UK primary care patients, identifying patients with NVAF who initiated rivaroxaban 20 mg/day or warfarin between January 2014 and March 2019.

Patients were excluded if they had a history of end-stage renal disease or a baseline estimated glomerular filtration rate (eGFR) of <50 ml/min/1.73m2, or if they had no eGFR or sCr values recorded in the year before initiation of OAC therapy.

The team included 5338 rivaroxaban patients, who had a mean age of 72.6 years and of whom 61% were male, alongside 6314 patients treated with warfarin. The latter had an average age of 73.2 years and 58% were male.

The mean eGFR at baseline was similar in the two groups, at 75.7 and 75.5 ml/min/1.73m2, and the proportion of patients with diabetes in the two groups  was 21% and 22%. Heart failure was present in 10% and 11% of participants in the respective treatment groups.

Adverse renal outcomes were defined as a doubling of sCr levels, an ≥30% decline in eGFR, and incident ESRD (end-stage renal disease), which included a code in the health record for ESRD, stage 5 chronic kidney disease, chronic dialysis, or an eGFR <15 ml/min/1.73m2.

Over an average follow-up of 2.5 years, 322 patients had doubling of sCr level, 1179 had a ≥30% decline in eGFR, and 22 were diagnosed with ESRD.

Study Findings

After adjusting for age, sex, baseline renal function and comorbidities, the researchers found that patients treated with rivaroxaban were significantly less likely than those treated with warfarin to experience a doubling of SCr levels, at a hazard ratio of 0.63 (p<0.05).

They were also significantly less likely to have a ≥30% decline in eGFR, at a hazard ratio of 0.76 (p<0.05). There was also a non-significant reduction in the incidence of ESRD with rivaroxaban versus warfarin.

Looking at the rate of decline of eGFR, the team found that, among 2054 rivaroxaban patients and 2464 given warfarin, the average decline in renal function over the study period was slower with rivaroxaban.

The estimated mean loss in renal function during the study period was 2.03 ml/min/1.73 m2 per year among warfarin users and 1.65 ml/min/1.73 m2 among patients taking rivaroxaban, at a mean difference on linear mixed regression analysis of 0.39 ml/min/1.73 m2 per year (p=0.03).

The study was funded by Bayer AG.

No relevant financial relationships declared.

ESC Congress 2021: Abstract Renal decline in patients with atrial fibrillation treated with rivaroxaban or warfarin: a population-based cohort study in the United Kingdom. Presented 27 August.

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