P4749Renal function worsening in factor-xa inhibitors vs phenprocoumon in patients with non-valvular atrial fibrillation and renal disease - insights from the RELOADED study

Abstract

Background Data on the effectiveness and safety of Factor-Xa non-vitamin-K oral anticoagulants in patients with non-valvular atrial fibrillation (NVAF) and renal disease is scarce. Among others, our study aimed to investigate the risk of renal function worsening in new users of NOACs vs. phenprocoumon with renal disease. Methods We conducted a new user cohort study (one year washout period) in patients with NVAF overall and additionally with renal disease defined by either an extended list of ICD-10 codes (definition 1) or chronic kidney disease (CKD) stages 3 or 4 (definition 2). German claims data between January 1st, 2013 and June 30th, 2017 were utilized and a multiple Cox-regression was performed to calculate confounder-adjusted hazard ratios (HRs) for the risk of end stage renal disease (ESRD)/dialysis and acute kidney injury in new users of NOACs (rivaroxaban, apixaban and edoxaban) vs. new users of phenprocoumon. Results In the overall population 22,339 patients initiating rivaroxaban, 16,201 patients initiating apixaban, 2,828 patients initiating edoxaban and 23,552 patients initiating phenprocoumon were included. NOAC patients with renal disease (definition 1) initiating reduced doses comprised 2,121 initiators of rivaroxaban, 2,507 of apixaban and 292 of edoxaban. 7,289 patients of phenprocoumon were identified. Patients with CKD (definition 2) initiating reduced doses of Factor-Xa inhibitors comprised 1,216 initiators of rivaroxaban, 1,522 of apixaban, 166 of edoxaban and 3,513 of phenprocoumon. In the confounder-adjusted analysis, a beneficial effect for both, rivaroxaban and apixaban over phenprocoumon was seen for the risk of ESRD/dialysis for all populations (overall, renal definition 1 and renal definition 2). In addition, in the CKD population we found a statistically significant risk reduction related to acute kidney injury only for rivaroxaban initiators (44%). There was not sufficient data to conduct the analyses for edoxaban. Figure 1 Conclusion This is the first observational retrospective database study evaluating the effect of renal function worsening in Germany. Results indicate a beneficial effect for both, reduced doses of rivaroxaban and apixaban related to renal function worsening over time when compared to phenprocoumon. This effect was more pronounced for the risk reduction with rivaroxaban related to ESRD /dialysis and specifically also related to a significant risk reduction for AKI. Acknowledgement/Funding The study was funded by Bayer AG

Renal decline in patients with non-valvular atrial fibrillation treated with rivaroxaban or warfarin: A population-based study from the United Kingdom

“…Similarly, the point estimate was indicative of a potential benefit effect of rivaroxaban on progression to ESRD, yet statistical power was limited to be able to detect a significant difference between exposure groups. Our findings are consistent with those from previous claims database studies in the United States (US) [10][11][12]26] and Germany, [13] especially with those from Yao and colleagues. [10] Stronger evidence for a beneficial effect of rivaroxaban over VKAs on progression to ESRD/ Stage 5 CKD, has been reported by others.…”

“…In the claims database study by Yao and colleagues, the significantly reduced risks of SCr doubling and the ≥30% decline in eGFR seen with rivaroxaban vs. warfarin, were not seen for apixaban, and there was no suggestion of any difference between apixaban and warfarin on the occurrence of ESRD. In the study by Bonnemeier et al, [13] both long-term use of rivaroxaban and apixaban were associated with a reduced risk of ESRD occurrence compared with phenprocoumon, yet the reduction was double the magnitude for rivaroxaban (66% vs. 33%).…”

“…[10] Stronger evidence for a beneficial effect of rivaroxaban over VKAs on progression to ESRD/ Stage 5 CKD, has been reported by others. [11] [13] Using the Marketscan database in the US, Coleman et al [11] reported a significant 18% reduction in progression to stage 5 CKD/dialysis for rivaroxaban vs. warfarin, while in Germany, Bonnemeier et al [13] found rivaroxaban to be associated with a significant 66% reduction in occurrence of ESRD when compared with phenprocoumon. Also using Marketscan, Vaitsiakhovich and colleagues [12] reported a 47% reduction in progression to stage 5 CKD/kidney failure/dialysis in rivaroxaban vs. warfarin users among patients with stage 3 or 4 CKD at baseline, as well as in those with type 2 diabetes, in line with findings from another Marketscan study restricted to patients with diabetes.…”

“…We used an intention-totreat (ITT) approach where patients were followed for their whole observation period irrespective of whether they discontinued their starting OAC or switched OAC. Separate follow-ups were undertaken to identify each adverse renal outcome of interest, which were chosen based on their use in previous RCTs [15][16][17] and observational studies [10][11][12][13] on this topic, thereby enabling comparison of results. These were doubling of SCr at any point during follow-up, ≥30% decline in eGFR (confirmed by a subsequent measurement), and incident ESRD (code for ESRD, stage 5 CKD, chronic dialysis, or eGFR <15 ml/min/ 1.73m 2 confirmed by a subsequent measurement).…”

“…[9] Previous observational studies based on the secondary data have found that patients with NVAF treated with NOACs have significantly lower risks of long-term adverse renal outcomes compared with those treated with a VKA. [10][11][12][13][14] However, limitations such as the absence of relevant demographic or lifestyle data in the claims databases used in some of these studies, hinders interpretation of the observed associations. Furthermore, findings from substudies of randomized controlled trials (RCTs) on this topic have been mixed but suggest there could be a differential influence between individual NOACs and warfarin on adverse renal outcomes.…”